Genetic counseling for glycogen storage disease -
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J Inherit Metab Dis ; 29 : — Gregory BL, Shelton GD, Bali DS, Chen YT, Fyfe JC. Glycogen storage disease type IIIa in curly-coated retrievers. J Vet Intern Med ; 21 : 40— Download references. This project was supported by educational grants from the Association for Glycogen Storage Disease, US, and the American College of Medical Genetics Foundation.
We thank Salvatore DeMauro, MD, Mark Tarnopolsky, MD, PhD, William Rhead, MD, Lane Rutledge, MD, Joseph Wolfsdorf, MD, and Yuan-Tsong Chen, MD, PhD, for their prepublication reviews of this guideline. Departments of Pediatrics, Duke University Medical Center, Durham, North Carolina.
Community and Family Medicine, Duke University Medical Center, Durham, North Carolina. Medicine, Duke University Medical Center, Durham, North Carolina. Department of Pediatrics, Nemours Children's Clinic, Jacksonville, Florida. Department of Pediatrics, Columbia University Medical Center, New York, New York.
Departments of Surgery and Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas. Departments of Neurology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida. American College of Medical Genetics, Bethesda, Maryland. You can also search for this author in PubMed Google Scholar.
Correspondence to Priya S Kishnani. Disclaimer: ACMG standards and guidelines are designed primarily as an educational resource for medical geneticists and other health care providers to help them provide quality medical genetic services.
Adherence to these standards and guidelines does not necessarily ensure a successful medical outcome. These standards and guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results.
In determining the propriety of any specific procedure or test, the geneticists should apply their own professional judgment to the specific clinical circumstances presented by the individual patient or specimen.
It may be prudent, however, to document in the patient's record the rationale for any significant deviation from these standards and guidelines. Reprints and permissions. Kishnani, P. et al. Glycogen Storage Disease Type III diagnosis and management guidelines. Genet Med 12 , — Download citation.
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Skip to main content Thank you for visiting nature. nature genetics in medicine acmg practice guideline article. Download PDF. Abstract Purpose: Glycogen storage disease type III is a rare disease of variable clinical severity affecting primarily the liver, heart, and skeletal muscle.
Glycogen storage diseases Article 07 September Diagnostic accuracy and the first genotype—phenotype correlation in glycogen storage disease type V Article 05 December Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring Article 02 July PURPOSE This guideline is intended as an educational resource.
Overview and general background GDE is one of the few known proteins with two independent catalytic activities occurring at separate sites on a single polypeptide chain. Target audience This guideline is directed at a wide range of providers.
Table 1 Differential diagnosis of GSD III Full size table. Table 2 Suggested laboratory evaluations for a patient with hypoglycemia and hepatomegaly Full size table.
Biochemical analysis of GDE activity and glycogen content Clinical assays measure overall GDE activity in the affected tissue samples. Table 3 Biochemical and histologic characteristics of selected GSD types Full size table. Ventricular hypertrophy and cardiomyopathy Individuals with GSD III do not develop valvular disease such as semilunar or atrioventricular valve regurgitation, but left ventricular hypertrophy LVH seems to be common in GSD III, although only a small fraction of individuals with GSD III actually develop cardiomyopathy symptomatic ventricular hypertrophy.
Routine evaluation and management Based on currently available data regarding cardiovascular involvement in GSD III, several recommendations for evaluation and management can be made.
Infants and young children with GSD IIIa and IIIb The initial focus of the diet for the infant and young child with either GSD IIIa or IIIb is to prevent hypoglycemia. Adults with GSD IIIa and IIIb The emphasis of the diet for the adult with GSD IIIa is on a higher percentage of protein.
Liver transplantation and organ allocation Although individuals with GSD III may develop histologic evidence of cirrhosis, so long as their synthetic function remains normal or well preserved, liver transplantation LT is not necessary.
Implications for muscle energy metabolism and exercise Muscle glycogen is a crucial fuel for anaerobic metabolism to support maximal effort and is broken down by myophosphorylase and muscle debranching enzyme.
Physical therapy Musculoskeletal assessment is recommended with respect to potential alterations in alignment described earlier hypermobility, increased width of base of support, anterior pelvic tilt, genu valgum and recurvatum, hindfoot valgus, and forefoot varus. GENERAL MEDICAL CARE General medical care should be individualized as disease manifestations vary.
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According to the aforementioned background, the present study aimed to identify the genetic background of GSDs in a small sample of Iranian patients by using targeted gene sequencing TGS to search for molecular etiology. To the best of our knowledge, this is the first study from Iran.
A total number of 14 pediatric patients were recruited in this retrospective observational case study. There were particular diagnosis features leading to their selection as GSD patients. Among them, six cases Parents of 13 patients The mean age of the disease onset was Elevated liver enzymes, i.
All clinical manifestations are summarized in Table 1. A total of genes of inherited metabolic diseases were included in this panel.
All coding regions for the genes were enriched in an unbiased fashion, with sufficient coverage. Each patient showed an average sequence variants. All the variants were identified by TGS, confirmed by Sanger sequencing for each patient Supplementary Table 1. Finally, the results showed to be concordant in terms of zygosity.
Diagnoses and zygosity of the 14 patients are illustrated in Table 2. Accordingly, one patient 6. Overall, 15 mutations were detected in the GSD-associated genes in 13 patients, 10 of whom had not been previously reported. These novel mutations included one frameshift variant in AGL c.
Moreover, there were seven missense variants, i. one in PGAM2 c. Two patients were also detected to have bi-allelic mutations; patient no. The most common defects were found in AGL GSD-III and PHKB GSD-IX. Allele frequency of all variants were searched in Iranome database public Iranian data set.
Only Patient no. Pathological results also indicated GSD-I with severe bridging fibrosis, diagnosed as cirrhosis. A novel homozygous nonsense variant, i. Tyr8Ter , was also detected in the SLC37A4 gene GSD type-Ib by TGS Table 2. No other deleterious variant was found in other GSD genes in the panel.
Patients no. Both patients were presented with hypoglycemia patient no. Histopathological findings were suggestive of type I or III GSD, with mild portal fibrosis.
The variants in the glycogen debranching enzyme gene, AGL, were also observed by TGS. A homozygous deleterious frameshift mutation, i. The liver biopsy from this case suggested GSD-I or III along with severe fibrosis. A novel pathogenic homozygote variant, c. LysLeufsTer14 , was also detected in the AGL gene.
This variant had not been listed in Iranome and gnomAD databases or described in the related literature. Another example of GSD-III was patient 5 , a 3-year-old boy, who presented with hepatomegaly, elevated TG, TChol, LDH, BCR, AST, and ALT. The liver biopsy diagnosis in this case was GSD-I or III with cirrhosis.
The targeted NGS also detected a homozygote variant, c. TrpTer , which had been previously reported 13 , In addition, the liver biopsy showed cirrhosis and suggested GSD-IV. He had also successfully received a partial liver transplant at the age of 2. Moreover, the targeted NGS panel revealed two variants in GBE1 gene.
A homozygous deleterious variant, namely c. GluVal 15 , and another novel homozygous variant c. Val98Leu , were additionally detected in the GBE1 gene. The new variant was not listed in Iranome and gnomAD databases or described in the related literature, so it could be interpreted as a variant of uncertain significance VUS.
Her liver biopsy also suggested unclassified GSD with marked fibrosis. Using TGS, a novel homozygous missense variant, c. GluGly , was detected in PYGL gene, indicating GSD-VI Table 2.
Para-clinical results also showed increased TG, TChol, BCR, AST, and ALT Table 1. Histopathological studies of his liver biopsy also suggested GSD-I or III with mild fibrosis. However, a homozygous pathogenic deletion variant, c.
Asp77del , was detected in the liver isoform glycogen phosphorylase, the PYGL gene Table 2 Her liver biopsy also showed unclassified GSD with fibrosis.
A homozygous pathogenic variant, c. Arg44Ter , was additionally detected in a PHKG2 gene by TGS. This missense mutation had been previously reported in patients with GSD-IXc 17 , 18 , The results of liver histopathological studies also showed unclassified GSD with bridging fibrosis.
Using TGS analysis additionally revealed a novel heterozygous variant, c. Leu45His , in the glycogen phosphorylase kinase regulatory sub-unit beta gene, PHKB GSD-IXb.
No other pathogenic variants were detected in other GSD genes in the panel. She was referred because of poor feeding at the age of 3. Laboratory investigations also showed elevated TG, TChol, LDH, Alb, AST, and ALT, as well as leukopenia and acidosis Table 1.
The liver biopsy revealed unclassified GSD, and moderate periportal fibrosis. She harbored three novel variants, namely one heterozygote variant c.
LeuPhe in the SLC37A4 gene and two homozygote variants c. and c. GlnArg in the PHKB gene. The pathogenic novel variant, c. As a result, she was most probably suffering from IXb, whose symptoms tended to appear with increasing age.
Histopathological studies of his liver biopsy also suggested unclassified GSD, with cirrhosis. Using TGS, a novel heterozygous variant, c. Arg5His , was detected in phosphoglycerate mutase gene, the PGAM2 GSD-X.
To note, GSD-X is an autosomal recessive disorder and the detection of a single heterozygous variant did not confirm the diagnosis. Nevertheless, lack of a second pathogenic allele or any identified pseudo-deficiency variant had left the molecular diagnosis of this patient in question.
Pulmonary hypertension, moderate mitral regurgitation, and mild tricuspid regurgitation were also observed. Moreover, the liver biopsy results revealed cirrhosis, which was suggestive of unclassified GSD. A novel heterozygous variant, c. MetLeu , was further detected in the PRKAG2 gene by TGS and implied PRKAG2 deficiency i.
GSD of heart—lethal congenital. Since the PRKAG2 deficiency is an autosomal dominant inheritance with full penetrance, single heterozygote variants could confirm all of her clinical, molecular, and biochemical results. The diagnosis of none of the GSD and non-GSD-associated genes was confirmed in patient no.
She was a 2-year-old girl, who presented with hepatomegaly, clubbed fingers, failure to thrive, diarrhea, vomiting, as well as high platelet count, AST, ALT and low uric acid Table 1. Her liver biopsy was suggestive of GSD or lipid storage disease with mild fibrosis.
No deleterious mutations were also detected in any of the related GSD genes analyzed. There was, therefore, no definite diagnosis for this patient. In five patients, the features of liver histopathology were suggestive of unclassified GSD, molecular genetic investigations of these patients which confirmed the diagnosis of GSD-VI in one patient no.
In one case, not only the features of liver histopathology were shown ambiguous results, but also no deleterious mutations were detected in any of the GSD genes analyzed no.
Classification and sub-typing of GSD patients are important steps towards personalized patient management, which can help clinicians practice the best and the most correct therapy with the fewest adverse events for patients Here, the first and largest cohort is reported about GSD sub-typing from the Middle East and Asia.
It is also the first study, addressing clinical characteristics and genomics in sub-typing of patients with GSDs from Iranian population.
In this cohort of 14 pediatric patients, 10 novel pathogenic variants in the SLC37A , AGL , GBE1 , PHKB , PGAM2 and PRKAG2 genes were found. Notably, GSD-IX was detected in three patients, which had not been reported from Iran, so far. It means that it has been overlooked in our population because of subtle patient presentations and self-limited outcomes as well as lack of molecular diagnosis analyses.
Therefore, it has been classified as other types of GSD, such as GSD-III or VI. Chronic liver diseases, such as cirrhosis and fibrosis, have been also rarely reported in some types of GSDs e.
GSD-VI and IX In addition, asymptomatic heart problems with liver involvement were identified in a GSD of the heart-lethal congenital disorder i. PRKAG2 deficiency in one patient in our study cohort.
To the best of our knowledge, we report for the first time liver cirrhosis in GSD-X and GSD of the heart-lethal congenital i. PRKAG2 deficiency. In this pathological report, 13 patients were suggestive to have one type of GSD without exact sub-typing, so molecular genetic analysis namely, targeted genome sequencing based on NGS was performed, confirming the exact type of GSD.
According to these results, molecular genetic testing, especially NGS-based GSD or inborn inherited metabolic panel exome sequencing, was recommended for definite diagnosis of GSD sub-types prior to invasive liver biopsy. Liver histopathology may also be a powerful and effective method for monitoring long-term liver complications and evaluating the status of the liver in these patients, but not for confirming diagnosis and accurate sub-typing.
NGS-based targeted exome sequencing is thus reported as the best future routine method of molecular diagnosis. This is especially useful for complex disorders with less specific clinical findings Nevertheless, in defining the syndromes or diseases like GSD, clinical features or biochemical phenotypes can effectively address a particular pathway or a group of genes responsible for the disease.
In such cases, a custom-targeted gene-sequencing panel has been confirmed to be an efficient as well as time- and cost-effective technique with high diagnostic yields Analytical workflows for the diagnosis of GSD diseases are not fully standardized; however, a useful and practical approach based on clinical and biochemical evaluations followed by targeted molecular analysis was reported later, as shown in Fig.
Moreover, using custom-target sequencing vs. exome sequencing would become a routine technique due to the focus on a limited number of suspected diseases and appropriate balance between the cost, time, throughput, and deep coverage, especially for low-income countries such as Iran To note, utilizing TGS panel is suitable to detect mutations, especially in communities with high numbers of consanguineous marriages such as Iran.
In this country, the prevalence rate of consanguineous marriage is approximately seen in Moreover, the samples from patients without a definite diagnosis would be recommended to be analyzed by genome sequencing or exome sequencing.
Integration of clinical and laboratory workflows to optimize hepatic glycogen storage disease diagnosis The present work revealed unexpected findings for two patients. However, in previous studies, reported manifestations had been less severe and essentially heart-specific, non-lysosomal glycogenosis, and mild-to-severe cardiac hypertrophy, enhancing the risk of sudden cardiac death in midlife without liver involvement 27 , This was the first patient with PRKAG2 gene mutation reported to have liver cirrhosis; however, a functionality of the novel variant remains underdiagnosed.
Another patient no. These two patients had atypical clinicopathological features, precluding accurate classification and diagnosis with clinicopathological features and in need of more specific genetic testing for definite diagnosis.
Despite genetic homogeneity, we found evidence of unusual features with novel variants. A possible reason for the high rate of novel variations we saw might be the lack of molecular genetic analysis before. It is known that mutations can have a specific race as well as restricted geographical or ethnical distribution, while was never analyzed such patients in our country.
In addition, the results of this study will help improve gene variant spectrum, diagnostic panels, clinical diagnosis, and patient management not only in this country but also in the region. A deeper knowledge of genomic variants also leads to better findings of determinants associated with the genotype—phenotype match in GSDs In conclusion, the study indicated the benefits of TGS method in diagnosing GSD, especially when the clinical findings were equivocal.
Given the cost- and time-efficiency of these methods, they can prevent the patients from receiving long-term improper treatments. The diagnosis of the patients reported here has helped expand the genetic and phenotypic spectrum of the GSDs disorders.
From March to December , a total number of 14 pediatric patients suspected to GSDs who presented with hepatomegaly, hypoglycemia, growth and development delay during childhood were selected at Shiraz Transplant Research Center STRC and Namazi Hospital Shiraz, Iran.
None of these 14 cases had molecular diagnoses. All the patients had already have liver biopsies with histopathological features, which suggested hepatic GSDs by the pathologist Liver biopsy was performed to determine the details of the liver pathology especially stage of fibrosis.
Two independent research team members reviewed electronic and paper charts for clinical features, biochemical investigations, histopathological results, and diagnostic imaging. Whole blood samples were collected from all study subjects and sent to the Pediatric Metabolic Diseases Laboratory, Gazi Hospital Ankara, Turkey for targeted NGS-based panel analysis.
The Ethics Committee of Shiraz University of Medical Sciences also approved this study Approval : IR. S , which was in accordance with the Declaration of Helsinki.
In brief, genomic DNA from 2 ml peripheral blood was extracted using AutoMate Express Nucleic Acid Extraction System Life Technologies, Guilford, CT, South San Francisco, CA, US. They were also hybridized and enriched for TGS. Then, Ion Torrent S5 platform was employed for DNA sequencing analysis.
A custom-targeted Ion AmpliSeq panel that included amplicons covering genes associated with Inborn Metabolic Diseases was used. Among genes, the GSD genes were also present in this panel which included the genes for Glycogen Storage Disorders with hepatic involvement such as G6PC Type Ia , SLC37A4 Type Ib , AGL Type III , GBE1 Type IV , PYGL Type VI , PHKA2 Type IXa , PHKB Type IXb , PHKG2 Type IXc and GLUT2 Type XI.
The other genes for gluconeogenesis, namely PC Pyruvate Carboxylase deficiency , PCK2 Phosphoenolpyruvate carboxykinase deficiency and FBP1 Fructose-1,6-bisphosphatase , were also present in this panel.
Analyses were done using an Ion Torrent chip Life Technologies, Guilford, CT, South San Francisco, CA. The results were analyzed with Ion Reporter Software Life Technologies, Guilford, CT, South San Francisco, CA, US as well as Integrated Genomic Viewer The human genome 19 was also used as the reference.
Polymorphism Phenotyping v2 PolyPhen2 , Scale-Invariant Feature Transform SIFT , and MutationTaster were further employed for in silico analysis. Genomic Evolutionary Rate Profiling GERP and the Phastcons scores were also utilized to evaluate the conservation of the variants.
The population frequency of each variation was correspondingly estimated using the data from the Genome Aggregation Database gnomAD and Iranome database The American College of Medical Genetics and Genomics ACMG guidelines were additionally used for variant interpretations The sequence variants were also described according to the Human Genome Variation Society Nomenclature Accession number of the relevant reference sequence s of GSD genes are presented in Supplementary File 1.
Direct Sanger sequencing was performed in all subjects for validation of the causal mutations in candidate genes. Primers were designed using OLIGO primers design v. All patients had undergone ultrasound-guided liver biopsy using the standard Tru-Cut biopsy needles.
All the slides were reviewed by an expert hepatopathologist B. Data were analyzed using SPSS Continuous data were presented as the mean and standard deviation SD or median and range.
The study was approved by the Bioethics Committee of the Medical University of Shiraz, Iran No. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions.
Hicks, J. Glycogen storage diseases: a brief review and update on clinical features, genetic abnormalities, pathologic features, and treatment. Article PubMed Google Scholar. Burda, P. Hepatic glycogen storage disorders: what have we learned in recent years?. Care 18 , 15— Article Google Scholar.
Vega, C. et al. Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing. Article CAS PubMed Google Scholar.
Wang, J. Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin.
Chen, Y. Glycogen Storage Diseases McGraw-Hill, Google Scholar. Beyzaei, Z. Molecular diagnosis of glycogen storage disease type I: a review. EXCLI J.
PubMed PubMed Central Google Scholar. Ng, S. Exome sequencing identifies the cause of a mendelian disorder. Boycott, M. Rare-disease genetics in the era of next-generation sequencing: discovery to translation. Nicastro, E. Next generation sequencing in pediatric hepatology and liver transplantation.
Liver Transpl. Capture-based high-coverage NGS: a powerful tool to uncover a wide spectrum of mutation types. Targeted capture and massively parallel sequencing of twelve human exomes. Nature , — Article CAS ADS PubMed PubMed Central Google Scholar.
Glycogen is the form of sugar your body stores in Isotonic drink for fitness liver and muscles for future energy needs. Glycogen storage diseases are storafe genetic Genegic in which Grilled chicken breast enzymes diwease ones involved in creating glycogen or breaking it down into sugar for your body to use -- are missing or don't work correctly. This can result in liver, heart, muscle, and respiratory problems. While there is no cure, our team of internationally recognized experts uses special diets and medical treatments to manage these diseases and their symptoms. We work you or your child to improve growth, development, and health.Weight management with better insulin sensitivity is ofr form of sugar your body stores in your liver and muscles for Gdnetic energy needs. Glycogen couseling diseases are complex genetic conditions Sports nutrition for injury prevention and recovery which certain enzymes -- ones involved glyocgen creating glycogen or diseaae it down into sugar for your body to use -- are missing or don't Grilled chicken breast correctly.
This can Grilled chicken breast in liver, heart, muscle, and respiratory Grilled chicken breast. Storaeg there Grilled chicken breast no Genetic counseling for glycogen storage disease, our team of internationally founseling experts uses special diets and etorage treatments to manage these diseases and their gljcogen.
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Typically, Genetic counseling for glycogen storage disease come glydogen Duke once to Geneti a glycoven for follow-up with our specialists. Living with glycogen fo disease means closely monitoring lab Cognitive development techniques results, as well Antioxidant foods and free radicals regular tests Genetic counseling for glycogen storage disease screening to diagnose complications when they arise.
Severe forms of glycogen storage disease xounseling damage the heart and lungs glyfogen cause infections. We dosease closely with your lgycogen doctors to follow Gendtic treatment plan and so gltcogen tests can be performed closer cisease home. The effects of some forms founseling glycogen storage disease can be reversed by Grilled chicken breast healthy levels of vitamins, minerals, and enzymes for proper growth and counsfling.
Sometimes a diseass tube is recommended counselong continuous feeding. People with glycogen storage disorders often work with Sports nutrition for vegetarians and occupational therapists to build strength and promote proper development.
These therapies can help you or your child with motor skills for tasks of daily living. Weakened muscles and developmental delays related to glycogen storage disorders can impact speech. Our speech pathologists use speech therapy to teach children how to make the correct mouth movements to improve their spoken words and language acquisition.
Surgery may be necessary if the liver, heart, or digestive tract is affected by the disease. If serious damage occurs, organ transplants may be recommended. We use family history and medical tests to diagnose glycogen storage diseases. Prenatal testing is also available.
The following tests may be ordered. May be used to monitor the health of the liver, kidneys, and muscles, and ensure proper blood sugar levels. Can uncover the presence of disease-causing genetic changes. It is used to check for certain disease markers and hereditary traits.
Tissue samples taken from the liver and muscle are studied to look for disease or abnormal cell function. Contrast-enhanced ultrasound, CT, and MRI create detailed pictures of the size, structure, and function of organs and vessels.
This nonsurgical alternative to a liver biopsy uses ultrasound to check for liver stiffness from scarring, called liver fibrosis.
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More Filters. Clear Filters Apply. Showing of Doctors. Diagnosing Glycogen Storage Disease. There are several types of glycogen storage disease.
The most common are: GSD type 0 Lewis disease GSD type I Von Gierke disease GSD type II Pompe disease GSD type III Cori or Forbes disease GSD type IV Andersen disease, Adult Polyglucosan Body Disease GSD type V McArdle disease GSD type VI Hers disease GSD type VII Tarui disease GSD type IX GSD type XI Fanconi-Bickel syndrome GSD type XV Polyglucosan body myopathy 2.
Our Locations. Duke Health offers locations throughout the Triangle. Find one near you. Find a Location. Managing the Complications of Glycogen Storage Diseases. Complications vary depending on the type of glycogen storage disease; however, they can include: Liver problems Low blood sugar Gastrointestinal concerns such as inflammatory bowel disease Growth and developmental delays Lung problems Heart problems Additional complications can include muscle disease, blood disorders, and kidney problems.
Call for an Appointment. Preventive Disease Monitoring Living with glycogen storage disease means closely monitoring lab test results, as well as regular tests and screening to diagnose complications when they arise. Best Children's Hospital in NC. Blood Tests May be used to monitor the health of the liver, kidneys, and muscles, and ensure proper blood sugar levels.
: Genetic counseling for glycogen storage disease| Ten UConn Law Grads Named James W. Cooper Fellows | Sign In to My Duke Health MyChart Don't have a My Duke Health MyChart account? Sign up now. If you have trouble logging in, have questions about how to use My Duke Health MyChart , need more information about your account, or need to contact customer service, please view our FAQs. Find a Glycogen Storage Diseases Doctor. Close Doctor Overlay. Search Doctors by Condition, Specialty or Keyword Clear Search Text. Filter Results. Filter Results Close Filters of Doctor Search. Located Near. Located Near You Remove User Location. Distance Distance 5 miles 10 miles 25 miles 50 miles Clear filter. Gender Provider's Gender Clear filter. Language Languages Clear filter. Age Group Patient's Age Clear filter. Type of Provider Filter by Provider Title Clear filter. More Filters. Clear Filters Apply. Showing of Doctors. Diagnosing Glycogen Storage Disease. There are several types of glycogen storage disease. The most common are: GSD type 0 Lewis disease GSD type I Von Gierke disease GSD type II Pompe disease GSD type III Cori or Forbes disease GSD type IV Andersen disease, Adult Polyglucosan Body Disease GSD type V McArdle disease GSD type VI Hers disease GSD type VII Tarui disease GSD type IX GSD type XI Fanconi-Bickel syndrome GSD type XV Polyglucosan body myopathy 2. Our Locations. Duke Health offers locations throughout the Triangle. Find one near you. Find a Location. Managing the Complications of Glycogen Storage Diseases. Complications vary depending on the type of glycogen storage disease; however, they can include: Liver problems Low blood sugar Gastrointestinal concerns such as inflammatory bowel disease Growth and developmental delays Lung problems Heart problems Additional complications can include muscle disease, blood disorders, and kidney problems. Call for an Appointment. Preventive Disease Monitoring Living with glycogen storage disease means closely monitoring lab test results, as well as regular tests and screening to diagnose complications when they arise. Best Children's Hospital in NC. Dagli AI, Lee PJ, Correia CE, et al. Pregnancy in glycogen storage disease type Ib: gestational care and report of first successful deliveries. Chou JY, Mansfield BC. Mutations in the glucosephosphatase-alpha G6PC gene that cause type Ia glycogen storage disease. Hum Mutat. Franco LM, Krishnamurthy V, Bali D, et al. Hepatocellular carcinoma in glycogen storage disease type Ia: a case series. Lewis R, Scrutton M, Lee P, Standen GR, Murphy DJ. Antenatal and Intrapartum care of a pregnant woman with glycogen storage disease type 1a. Eur J Obstet Gynecol Reprod Biol. Ekstein J, Rubin BY, Anderson, et al. Mutation frequencies for glycogen storage disease in the Ashkenazi Jewish Population. Am J Med Genet A. Melis D, Parenti G, Della Casa R, et al. Brain Damage in glycogen storage disease type I. J Pediatr. Rake JP, Visser G, Labrune, et al. Guidelines for management of glycogen storage disease type I-European study on glycogen storage disease type I ESGSD I. Eur J Pediatr. Rake JP Visser G, Labrune P, et al. Glycogen storage disease type I: diagnosis, management, clinical course and outcome. Results of the European study on glycogen storage disease type I EGGSD I. Eur J Pediat. Chou JY, Matern D, Mansfield, et al. Type I glycogen Storage diseases: disorders of the glucosePhosphatase complex. Curr Mol Med. Schwahn B, Rauch F, Wendel U, Schonau E. Low bone mass in glycogen storage disease type 1 is associated with reduced muscle force and poor metabolic control. Visser G, Rake JP, Labrune P, et al. Consensus guidelines for management of glycogen storage disease type 1b. Results of the European study on glycogen storage disease type I. Weinstein DA and Wolfsdorf JI. Effect of continuous gucose therapy with uncooked cornstarch on the long-term clinical course of type 1a glycogen storage disease. Eur J Pediatr ; Janecke AR, Mayatepek E, and Utermann G. Molecular genetics of type I glycogen storage disease. Mol Genet Metab. Viser G, Rake JP, Fernandes, et al. Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen storage disease type 1b: results of the European study on glycogen storage disease type I. Chen YT, Bazarre CH, Lee MM, et al. Type I glycogen storage disease: nine years of management with corn starch. INTERNET Bali DS, Chen YT, Austin S, et al. Glycogen Storage Disease Type I. In: Adam MP, Ardinger HH, Pagon RA, et al. GeneReviews® [Internet]. Seattle WA : University of Washington, Seattle; NORD strives to open new assistance programs as funding allows. NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations. This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder. Rare Disease Database. Glycogen Storage Disease Type I Print. Acknowledgment NORD gratefully acknowledges Deeksha Bali, PhD, Professor, Division of Medical genetics, Department of Pediatrics, Duke Health; Co-Director, Biochemical Genetics Laboratories, Duke University Health System, and Yuan-Tsong Chen, MD, PhD, Professor, Division of Medical Genetics, Department of Pediatrics, Duke Medicine; Distinguished Research Fellow, Academia Sinica Institute of Biomedical Sciences, Taiwan for assistance in the preparation of this report. Disease Overview Glycogen storage diseases are a group of disorders in which stored glycogen cannot be metabolized into glucose to supply energy and to maintain steady blood glucose levels for the body. Detailed evaluations may be useful for a differential diagnosis: Forbes or Cori disease GSD-III is one of several glycogen storage disorders that are inherited as autosomal recessive traits. Genetic counseling is recommended for affected individuals and their families. For information about clinical trials being conducted at the National Institutes of Health NIH in Bethesda, MD, contact the NIH Patient Recruitment Office: Tollfree: TTY: Email: prpl cc. Additional Assistance Programs MedicAlert Assistance Program NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations. Rare Caregiver Respite Program This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder. Association for Glycogen Storage Disease AGSD. Email: info agsdus. Related Rare Diseases: Adult Polyglucosan Body Disease , Danon Disease , Pompe Disease , Metabolic Support UK. Email: contact metabolicsupportuk. Related Rare Diseases: Glucose-Galactose Malabsorption , Sandhoff Disease , Aromatic L-Amino Acid Decarboxylase Deficiency , Phone: Email: NDDIC info. Association for Glycogen Storage Disease UK Ltd. Phone: Email: info agsd. Related Rare Diseases: Adult Polyglucosan Body Disease , Pompe Disease , Glycogen Storage Disease Type VI , Phone: Email: info curegsd. org Fax: Related Rare Diseases: Glycogen Storage Disease Type VI , Glycogen Storage Disease Type 7 , Glycogen Storage Disease Type IX , Sign Up for NORD News. Your Name Required. Your Email Required. I show my stripes for Required Max. Photo Required Max file size 5MB. image size px X px. Drop files here or Select files. Your Message Required Max. I agree to the terms and conditions. When you submit content or information to NORD, you are allowing the public to access and use that information, and to associate it with you. We take your privacy very seriously. 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| Glycogen Storage Disease Type III diagnosis and management guidelines | Prior to the treatment, Watts was consuming more than grams of cornstarch per day. One of the biggest reliefs from this gene therapy is I can now sleep through the night without worrying about dying in the middle of the night. I wake up 6 to 7 hours later with normal blood sugar. In addition to Watts, two other clinical trial cohort patients are seeing promising results on the lower cornstarch daily regimens. All three will participate in the next phase — a 4-year follow-up clinical trial study. In addition, three patients are enrolled in clinical trial testing a higher gene therapy dose. GSD Type Ia, affects an estimated 6, patients worldwide, which is caused by a defective gene for the enzyme glucosephosphatase-α G6Pase-α that controls sugar release from the liver. The condition was almost always fatal until , when it was discovered that continuous glucose therapy could help these patients. Cornstarch therapy was introduced as a slow release form of glucose in , and it allowed feeds to be spaced to every three to four hours. Thanks to cornstarch, a greater number of patients with GSD are now surviving into adulthood. February 14, UConn Today. News Series. Archives Contact Us. UConn University of Connecticut. Search University of Connecticut Search UConn. A to Z Index UConn A to Z Search. AAV vectors transduced liver and kidney in GSD Ia and striated muscle in GSD II mice to replace the deficient enzyme in each disease. Gene therapy has been advanced to early phase clinical trials for the replacement of G6Pase in GSD Ia and GAA in GSD II Pompe disease. Other GSDs have been treated in proof-of-concept studies, including GSD III, IV and V. The future of gene therapy appears promising for the GSDs, promising to provide more efficacious therapy for these disorders in the foreseeable future. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals. permissions oup. Abstract The focus of this review is the development of gene therapy for glycogen storage diseases GSDs. |
| Description | NGS has been applied in clinical diagnostics for Genetid diversity of symptoms to characterize the inherent disesse cause Grilled chicken breast diseases 8. Eur J Pediatr Genetic counseling for glycogen storage disease forr 1 : S97—S nature genetics in medicine acmg practice guideline article. To evaluate the patients with particular diagnosis features characterizing GSD, an observational retrospective case study was designed by performing a targeted gene sequencing TGS for accurate subtyping. In: Milunsky A, Milunsky J, eds. References Hicks, J. Other GSDs have been treated in proof-of-concept studies, including GSD III, IV and V. |
| Recent Articles | Individuals with GSD III do not develop valvular disease such as semilunar or atrioventricular valve regurgitation, but left ventricular hypertrophy LVH seems to be common in GSD III, although only a small fraction of individuals with GSD III actually develop cardiomyopathy symptomatic ventricular hypertrophy. Low bone mass in glycogen storage disease type 1 is associated with reduced muscle force and poor metabolic control. A possible reason for the high rate of novel variations we saw might be the lack of molecular genetic analysis before. These enzymes are normally produced by the pancreas and are important in the digestion of fats, proteins, and sugars. Clin Endocrinol Oxf ; 42 : — Orphanet J. J Inherit Metab Dis ; 18 : — |
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Pompe disease - causes, symptoms, diagnosis, treatment, pathologyGenetic counseling for glycogen storage disease -
The sensitivity of this panel will vary based on the clinical phenotype of the patient. Analytical sensitivity of this test is expected to be high as the majority of pathogenic variants reported in the genes in the panel are detectable via direct sequencing.
This panel typically provides PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions where applicable.
Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available i. We offer several options when ordering sequencing tests.
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Test Method Exome Sequencing with CNV Detection New York State Approved Test. PANEL AVAILABLE VIA PGnome Sequencing.
Reflex to PGxome AVAILABLE FOR THIS PANEL. EMAIL CONTACTS Genetic Counselors Genetic Counselor Team Geneticist Maxime Cadieux-Dion, PhD. Turnaround Time 3 weeks on average for standard orders or 2 weeks on average for STAT orders. Indications for Test Genetic testing for Glycogen Storage Diseases GSDs and disorders of glucose metabolism with a similar clinical presentation to the GSDs is available for patients suspected to be affected with one of these disorders.
This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary. Genes Official Gene Symbol OMIM ID AGL ALDOA ALDOB ENO3 EPM2A FBP1 G6PC1 GAA GBE1 GYG1 GYS1 GYS2 LAMP2 LDHA NHLRC1 PC PCK1 PCK2 PFKM PGAM2 PGM1 PHKA1 PHKA2 PHKB PHKG2 PRKAG2 PRKAG3 PYGL PYGM RBCK1 SLC16A1 SLC2A2 SLC37A4 Inheritance Abbreviation Autosomal Dominant AD Autosomal Recessive AR X-Linked XL Mitochondrial MT.
Adeva-Andany et al. PubMed ID: Burda and Hochuli PubMed ID: Cenacchi et al. PubMed ID: Chang et al. PubMed ID: DiMauro and Spiegel PubMed ID: Herbert et al. PubMed ID: Hicks et al. PubMed ID: Kilimann and Oldfors PubMed ID: Ozen.
PubMed ID: Santer et al. PubMed ID: Scalco et al. These features also preclude a specific clinical diagnosis, requiring more accurate paraclinical tests. To evaluate the patients with particular diagnosis features characterizing GSD, an observational retrospective case study was designed by performing a targeted gene sequencing TGS for accurate subtyping.
A total of the 14 pediatric patients were admitted to our hospital and referred for molecular genetic testing using TGS. Seven genes namely SLC37A4 , AGL , GBE1 , PYGL , PHKB , PGAM2 , and PRKAG2 were detected to be responsible for the onset of the clinical symptoms. A total number of 15 variants were identified i.
mostly loss-of-function LoF variants, of which 10 variants were novel. Finally, diagnosis of GSD types Ib, III, IV, VI, IXb, IXc, X, and GSD of the heart, lethal congenital was made in 13 out of the 14 patients. Notably, GSD-IX and GSD of the heart-lethal congenital i. PRKAG2 deficiency patients have been reported in Iran for the first time which shown the development of liver cirrhosis with novel variants.
These results showed that TGS, in combination with clinical, biochemical, and pathological hallmarks, could provide accurate and high-throughput results for diagnosing and sub-typing GSD and related diseases. Glycogen storage diseases GSDs are known as a group of disorders characterized by genetic errors leading to accumulation of glycogen in various tissues 1.
However, accurate identification of the sub-types of GSDs, especially hepatic forms, is not an easy task for clinicians and pathologists because of their similar and overlapping features as well as wide phenotypic variations 3. It is known that early diagnosis is important for proper treatment of patients to decrease organ damage and to increase life expectancy 4.
The diagnosis of GSDs mostly depends on paraclinical, clinical and biochemical assays 5. Molecular analysis, based on DNA testing, similarly permits accurate diagnosis when enzymological and pathological results are equivocal or unavailable 6. NGS has been applied in clinical diagnostics for a diversity of symptoms to characterize the inherent genetic cause of diseases 8.
Although single-gene testing and gene panels for specific disorders are still being used, NGS is progressively being utilized in diagnostic evaluation, especially for disorders that are genetically heterogeneous, such as GSDs 9 , Currently, targeted gene sequencing TGS panels have gained popularity for heterogeneous genetic anomalies in monogenic disorders MDs because of their time- and cost-effectiveness as well as their ability in simultaneous detection of common and rare genetic variations According to the aforementioned background, the present study aimed to identify the genetic background of GSDs in a small sample of Iranian patients by using targeted gene sequencing TGS to search for molecular etiology.
To the best of our knowledge, this is the first study from Iran. A total number of 14 pediatric patients were recruited in this retrospective observational case study.
There were particular diagnosis features leading to their selection as GSD patients. Among them, six cases Parents of 13 patients The mean age of the disease onset was Elevated liver enzymes, i. All clinical manifestations are summarized in Table 1.
A total of genes of inherited metabolic diseases were included in this panel. All coding regions for the genes were enriched in an unbiased fashion, with sufficient coverage.
Each patient showed an average sequence variants. All the variants were identified by TGS, confirmed by Sanger sequencing for each patient Supplementary Table 1. Finally, the results showed to be concordant in terms of zygosity. Diagnoses and zygosity of the 14 patients are illustrated in Table 2.
Accordingly, one patient 6. Overall, 15 mutations were detected in the GSD-associated genes in 13 patients, 10 of whom had not been previously reported. These novel mutations included one frameshift variant in AGL c. Moreover, there were seven missense variants, i.
one in PGAM2 c. Two patients were also detected to have bi-allelic mutations; patient no. The most common defects were found in AGL GSD-III and PHKB GSD-IX. Allele frequency of all variants were searched in Iranome database public Iranian data set.
Only Patient no. Pathological results also indicated GSD-I with severe bridging fibrosis, diagnosed as cirrhosis. A novel homozygous nonsense variant, i. Tyr8Ter , was also detected in the SLC37A4 gene GSD type-Ib by TGS Table 2.
No other deleterious variant was found in other GSD genes in the panel. Patients no. Both patients were presented with hypoglycemia patient no. Histopathological findings were suggestive of type I or III GSD, with mild portal fibrosis. The variants in the glycogen debranching enzyme gene, AGL, were also observed by TGS.
A homozygous deleterious frameshift mutation, i. The liver biopsy from this case suggested GSD-I or III along with severe fibrosis. A novel pathogenic homozygote variant, c.
LysLeufsTer14 , was also detected in the AGL gene. This variant had not been listed in Iranome and gnomAD databases or described in the related literature. Another example of GSD-III was patient 5 , a 3-year-old boy, who presented with hepatomegaly, elevated TG, TChol, LDH, BCR, AST, and ALT.
The liver biopsy diagnosis in this case was GSD-I or III with cirrhosis. The targeted NGS also detected a homozygote variant, c. TrpTer , which had been previously reported 13 , In addition, the liver biopsy showed cirrhosis and suggested GSD-IV.
He had also successfully received a partial liver transplant at the age of 2. Moreover, the targeted NGS panel revealed two variants in GBE1 gene. A homozygous deleterious variant, namely c.
GluVal 15 , and another novel homozygous variant c. Val98Leu , were additionally detected in the GBE1 gene. The new variant was not listed in Iranome and gnomAD databases or described in the related literature, so it could be interpreted as a variant of uncertain significance VUS. Her liver biopsy also suggested unclassified GSD with marked fibrosis.
Using TGS, a novel homozygous missense variant, c. GluGly , was detected in PYGL gene, indicating GSD-VI Table 2. Para-clinical results also showed increased TG, TChol, BCR, AST, and ALT Table 1.
Histopathological studies of his liver biopsy also suggested GSD-I or III with mild fibrosis. However, a homozygous pathogenic deletion variant, c.
Asp77del , was detected in the liver isoform glycogen phosphorylase, the PYGL gene Table 2 Her liver biopsy also showed unclassified GSD with fibrosis. A homozygous pathogenic variant, c. Arg44Ter , was additionally detected in a PHKG2 gene by TGS. This missense mutation had been previously reported in patients with GSD-IXc 17 , 18 , The results of liver histopathological studies also showed unclassified GSD with bridging fibrosis.
Using TGS analysis additionally revealed a novel heterozygous variant, c. Leu45His , in the glycogen phosphorylase kinase regulatory sub-unit beta gene, PHKB GSD-IXb.
No other pathogenic variants were detected in other GSD genes in the panel. She was referred because of poor feeding at the age of 3. Laboratory investigations also showed elevated TG, TChol, LDH, Alb, AST, and ALT, as well as leukopenia and acidosis Table 1.
The liver biopsy revealed unclassified GSD, and moderate periportal fibrosis. She harbored three novel variants, namely one heterozygote variant c. LeuPhe in the SLC37A4 gene and two homozygote variants c. and c.
GlnArg in the PHKB gene. The pathogenic novel variant, c. As a result, she was most probably suffering from IXb, whose symptoms tended to appear with increasing age.
Histopathological studies of his liver biopsy also suggested unclassified GSD, with cirrhosis. Using TGS, a novel heterozygous variant, c. Arg5His , was detected in phosphoglycerate mutase gene, the PGAM2 GSD-X.
To note, GSD-X is an autosomal recessive disorder and the detection of a single heterozygous variant did not confirm the diagnosis. Nevertheless, lack of a second pathogenic allele or any identified pseudo-deficiency variant had left the molecular diagnosis of this patient in question.
Pulmonary hypertension, moderate mitral regurgitation, and mild tricuspid regurgitation were also observed. Moreover, the liver biopsy results revealed cirrhosis, which was suggestive of unclassified GSD.
A novel heterozygous variant, c. MetLeu , was further detected in the PRKAG2 gene by TGS and implied PRKAG2 deficiency i.
GSD of heart—lethal congenital. Since the PRKAG2 deficiency is an autosomal dominant inheritance with full penetrance, single heterozygote variants could confirm all of her clinical, molecular, and biochemical results.
The diagnosis of none of the GSD and non-GSD-associated genes was confirmed in patient no. She was a 2-year-old girl, who presented with hepatomegaly, clubbed fingers, failure to thrive, diarrhea, vomiting, as well as high platelet count, AST, ALT and low uric acid Table 1.
Her liver biopsy was suggestive of GSD or lipid storage disease with mild fibrosis. No deleterious mutations were also detected in any of the related GSD genes analyzed. There was, therefore, no definite diagnosis for this patient.
In five patients, the features of liver histopathology were suggestive of unclassified GSD, molecular genetic investigations of these patients which confirmed the diagnosis of GSD-VI in one patient no. In one case, not only the features of liver histopathology were shown ambiguous results, but also no deleterious mutations were detected in any of the GSD genes analyzed no.
Classification and sub-typing of GSD patients are important steps towards personalized patient management, which can help clinicians practice the best and the most correct therapy with the fewest adverse events for patients Here, the first and largest cohort is reported about GSD sub-typing from the Middle East and Asia.
It is also the first study, addressing clinical characteristics and genomics in sub-typing of patients with GSDs from Iranian population. In this cohort of 14 pediatric patients, 10 novel pathogenic variants in the SLC37A , AGL , GBE1 , PHKB , PGAM2 and PRKAG2 genes were found.
Notably, GSD-IX was detected in three patients, which had not been reported from Iran, so far. It means that it has been overlooked in our population because of subtle patient presentations and self-limited outcomes as well as lack of molecular diagnosis analyses.
Therefore, it has been classified as other types of GSD, such as GSD-III or VI. Chronic liver diseases, such as cirrhosis and fibrosis, have been also rarely reported in some types of GSDs e.
GSD-VI and IX In addition, asymptomatic heart problems with liver involvement were identified in a GSD of the heart-lethal congenital disorder i.
PRKAG2 deficiency in one patient in our study cohort. To the best of our knowledge, we report for the first time liver cirrhosis in GSD-X and GSD of the heart-lethal congenital i. PRKAG2 deficiency. In this pathological report, 13 patients were suggestive to have one type of GSD without exact sub-typing, so molecular genetic analysis namely, targeted genome sequencing based on NGS was performed, confirming the exact type of GSD.
According to these results, molecular genetic testing, especially NGS-based GSD or inborn inherited metabolic panel exome sequencing, was recommended for definite diagnosis of GSD sub-types prior to invasive liver biopsy.
Liver histopathology may also be a powerful and effective method for monitoring long-term liver complications and evaluating the status of the liver in these patients, but not for confirming diagnosis and accurate sub-typing.
NGS-based targeted exome sequencing is thus reported as the best future routine method of molecular diagnosis. This is especially useful for complex disorders with less specific clinical findings Nevertheless, in defining the syndromes or diseases like GSD, clinical features or biochemical phenotypes can effectively address a particular pathway or a group of genes responsible for the disease.
In the form of the condition that affects the liver, the signs and symptoms usually improve with age. Typically, individuals catch up developmentally, and adults reach normal height. However, some affected individuals have a buildup of scar tissue fibrosis in the liver, which can rarely progress to irreversible liver disease cirrhosis.
GSD IX can affect muscle tissue, although this form of the condition is very rare and not well understood. The features of this form of the condition can appear anytime from childhood to adulthood. Affected individuals may experience fatigue, muscle pain, and cramps, especially during exercise exercise intolerance.
Most affected individuals have muscle weakness that worsens over time. GSD IX can cause myoglobinuria, which occurs when muscle tissue breaks down abnormally and releases a protein called myoglobin that is excreted in the urine.
Myoglobinuria can cause the urine to be red or brown. In a small number of people with GSD IX, the liver and muscles are both affected. These individuals develop a combination of the features described above, although the muscle problems are usually mild.
GSD IX that affects the liver is estimated to occur in 1 in , people. The forms of the disease that affect muscles or both muscles and liver are much less common, although the prevalence is unknown. Mutations in the PHKA1 , PHKA2 , PHKB , or PHKG2 genes are known to cause GSD IX. These genes provide instructions for making pieces subunits of an enzyme called phosphorylase b kinase.
The enzyme is made up of 16 subunits, four each of the alpha, beta, gamma, and delta subunits. At least two different versions of phosphorylase b kinase are formed from the subunits: one is most abundant in liver cells and the other in muscle cells.
The PHKA1 and PHKA2 genes provide instructions for making alpha subunits of phosphorylase b kinase. The protein produced from the PHKA1 gene is a subunit of the muscle enzyme, while the protein produced from the PHKA2 gene is part of the liver enzyme.
The PHKB gene provides instructions for making the beta subunit, which is found in both the muscle and the liver. The PHKG2 gene provides instructions for making the gamma subunit of the liver enzyme. Whether in the liver or the muscles, phosphorylase b kinase plays an important role in providing energy for cells.
The main source of cellular energy is a simple sugar called glucose. Glucose is stored in muscle and liver cells in a form called glycogen. Glycogen can be broken down rapidly when glucose is needed, for instance to maintain normal levels of glucose in the blood between meals or for energy during exercise.
Phosphorylase b kinase turns on activates the enzyme that breaks down glycogen. Although the effects of gene mutations on the respective protein subunits are unknown, mutations in the PHKA1 , PHKA2 , PHKB , and PHKG2 genes reduce the activity of phosphorylase b kinase in liver or muscle cells and in blood cells.
Reduction of this enzyme's function impairs glycogen breakdown. As a result, glycogen accumulates in and damages cells, and glucose is not available for energy.
Glycogen accumulation in the liver leads to hepatomegaly, and the liver's inability to break down glycogen for glucose contributes to hypoglycemia and ketosis. Reduced energy production in muscle cells leads to muscle weakness, pain, and cramping.
Official websites use. Gneetic A. gov website belongs Genetic counseling for glycogen storage disease an official couunseling organization in sorage United States. gov website. Share sensitive information only on official, secure websites. Glycogen storage disease type IX also known as GSD IX is a condition caused by the inability to break down a complex sugar called glycogen.
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