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Glycogen storage disease, type VI(GSD6)

MedGen UID:
6643
•Concept ID:
C0017925
•
Disease or Syndrome
Synonyms: Glycogen storage disease type 6; GSD VI; GSD6; Hepatic glycogen phosphorylase deficiency; Hers disease; Phosphorylase deficiency glycogen-storage disease of liver
SNOMED CT: Glycogen storage disease, type VI (29291001); Hepatic phosphorylase deficiency (29291001); Hers disease (29291001); GSD VI (29291001); Hepatic glycogen phosphorylase deficiency (29291001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
•Concept ID:
C0441748
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (Orphanet)
 
Gene (location): PYGL (14q22.1)
 
Monarch Initiative: MONDO:0009294
OMIM®: 232700
Orphanet: ORPHA369

Disease characteristics

Excerpted from the GeneReview: Glycogen Storage Disease Type VI
Glycogen storage disease type VI (GSD VI) is a disorder of glycogenolysis caused by deficiency of hepatic glycogen phosphorylase. This critical enzyme catalyzes the rate-limiting step in glycogen degradation, and deficiency of the enzyme in the untreated child is characterized by hepatomegaly, poor growth, ketotic hypoglycemia, elevated hepatic transaminases, hyperlipidemia, and low prealbumin level. GSD VI is usually a relatively mild disorder that presents in infancy and childhood; rare cases of more severe disease manifesting with recurrent hypoglycemia and marked hepatomegaly have been described. More common complications in the setting of suboptimal metabolic control include short stature, delayed puberty, osteopenia, and osteoporosis. Hepatic fibrosis commonly develops in GSD VI, but cirrhosis and hypertrophic cardiomyopathy are rare. Clinical and biochemical abnormalities may decrease with age, but ketosis and hypoglycemia can continue to occur. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Emma Labrador  |  David A Weinstein   view full author information

Additional description

From MedlinePlus Genetics
Glycogen storage disease type VI (also known as GSDVI or Hers disease) is an inherited disorder caused by an inability to break down a complex sugar called glycogen in liver cells. A lack of glycogen breakdown interferes with the normal function of the liver.

The signs and symptoms of GSDVI typically begin in infancy to early childhood. The first sign is usually an enlarged liver (hepatomegaly). During prolonged periods without food (fasting), affected individuals may have low blood sugar (hypoglycemia) or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars are unavailable. Children with GSDVI tend to grow slower than their peers, but they often achieve normal height as adults. Some affected children also have mild delays in the development of motor skills, such as sitting, standing, or walking.

The signs and symptoms of GSDVI tend to improve with age; most adults with this condition do not have any related health problems.  https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-vi

Clinical features

From HPO
Postnatal growth retardation
MedGen UID:
395343
•Concept ID:
C1859778
•
Finding
Slow or limited growth after birth.
See: Feature record | Search on this feature
Failure to thrive in infancy
MedGen UID:
358083
•Concept ID:
C1867873
•
Finding
See: Feature record | Search on this feature
Hepatomegaly
MedGen UID:
42428
•Concept ID:
C0019209
•
Finding
Abnormally increased size of the liver.
See: Feature record | Search on this feature
Increased hepatic glycogen content
MedGen UID:
344698
•Concept ID:
C1856285
•
Finding
An increase in the amount of glycogen stored in hepatocytes compared to normal.
See: Feature record | Search on this feature
Hypercholesterolemia
MedGen UID:
5687
•Concept ID:
C0020443
•
Disease or Syndrome
An increased concentration of cholesterol in the blood.
See: Feature record | Search on this feature
Hyperlipidemia
MedGen UID:
5692
•Concept ID:
C0020473
•
Disease or Syndrome
An elevated lipid concentration in the blood.
See: Feature record | Search on this feature
Hypoglycemia
MedGen UID:
6979
•Concept ID:
C0020615
•
Disease or Syndrome
A decreased concentration of glucose in the blood.
See: Feature record | Search on this feature
Hypertriglyceridemia
MedGen UID:
167238
•Concept ID:
C0813230
•
Finding
An abnormal increase in the level of triglycerides in the blood.
See: Feature record | Search on this feature
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
•Concept ID:
C1848701
•
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
See: Feature record | Search on this feature
Reduced hepatic glycogen phosphorylase activity
MedGen UID:
1053464
•Concept ID:
CN378331
•
Finding
Activity or concentration of glycogen phosphorylase L in the liver below the lower limit of normal.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGlycogen storage disease, type VI
Follow this link to review classifications for Glycogen storage disease, type VI in Orphanet.

Professional guidelines

PubMed

Diagnosis and follow-up of glycogen storage disease (GSD) type VI from the largest GSD center in China.
Luo X, Duan Y, Fang D, Sun Y, Xiao B, Zhang H, Han L, Liang L, Gong Z, Gu X, Yu Y, Qiu W
Hum Mutat 2022 May;43(5):557-567. Epub 2022 Feb 24 doi: 10.1002/humu.24345. PMID: 35143115
Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).
Kishnani PS, Goldstein J, Austin SL, Arn P, Bachrach B, Bali DS, Chung WK, El-Gharbawy A, Brown LM, Kahler S, Pendyal S, Ross KM, Tsilianidis L, Weinstein DA, Watson MS; ACMG Work Group on Diagnosis and Management of Glycogen Storage Diseases Type VI and IX
Genet Med 2019 Apr;21(4):772-789. Epub 2019 Jan 19 doi: 10.1038/s41436-018-0364-2. PMID: 30659246

Recent clinical studies

Etiology

Liver transplantation in glycogen storage disease: a single-center experience.
Beyzaei Z, Shamsaeefar A, Kazemi K, Nikeghbalian S, Bahador A, Dehghani M, Malekhosseini SA, Geramizadeh B
Orphanet J Rare Dis 2022 Mar 21;17(1):127. doi: 10.1186/s13023-022-02284-y. PMID: 35313948Free PMC Article
Liver histology in children with glycogen storage disorders type VI and IX.
Degrassi I, Deheragoda M, Creegen D, Mundy H, Mustafa A, Vara R, Hadzic N
Dig Liver Dis 2021 Jan;53(1):86-93. Epub 2020 Jun 4 doi: 10.1016/j.dld.2020.04.017. PMID: 32505569
Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review.
Lu SQ, Feng JY, Liu J, Xie XB, Lu Y, Abuduxikuer K
J Pediatr Endocrinol Metab 2020 Sep 7;33(10):1321-1333. doi: 10.1515/jpem-2020-0173. PMID: 32892177
Glycogen storage disease type VI: clinical course and molecular background.
Aeppli TR, Rymen D, Allegri G, Bode PK, Häberle J
Eur J Pediatr 2020 Mar;179(3):405-413. Epub 2019 Nov 26 doi: 10.1007/s00431-019-03499-1. PMID: 31768638
Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).
Kishnani PS, Goldstein J, Austin SL, Arn P, Bachrach B, Bali DS, Chung WK, El-Gharbawy A, Brown LM, Kahler S, Pendyal S, Ross KM, Tsilianidis L, Weinstein DA, Watson MS; ACMG Work Group on Diagnosis and Management of Glycogen Storage Diseases Type VI and IX
Genet Med 2019 Apr;21(4):772-789. Epub 2019 Jan 19 doi: 10.1038/s41436-018-0364-2. PMID: 30659246

Diagnosis

Liver transplantation in glycogen storage disease: a single-center experience.
Beyzaei Z, Shamsaeefar A, Kazemi K, Nikeghbalian S, Bahador A, Dehghani M, Malekhosseini SA, Geramizadeh B
Orphanet J Rare Dis 2022 Mar 21;17(1):127. doi: 10.1186/s13023-022-02284-y. PMID: 35313948Free PMC Article
Diagnosis and follow-up of glycogen storage disease (GSD) type VI from the largest GSD center in China.
Luo X, Duan Y, Fang D, Sun Y, Xiao B, Zhang H, Han L, Liang L, Gong Z, Gu X, Yu Y, Qiu W
Hum Mutat 2022 May;43(5):557-567. Epub 2022 Feb 24 doi: 10.1002/humu.24345. PMID: 35143115
Features of chinese patients with sitosterolemia.
Zhou Z, Su X, Cai Y, Ting TH, Zhang W, Lin Y, Xu A, Mao X, Zeng C, Liu L, Li X
Lipids Health Dis 2022 Jan 18;21(1):11. doi: 10.1186/s12944-021-01619-1. PMID: 35042526Free PMC Article
The Phenotypic and Genetic Spectrum of Glycogen Storage Disease Type VI.
Grünert SC, Hannibal L, Spiekerkoetter U
Genes (Basel) 2021 Aug 3;12(8) doi: 10.3390/genes12081205. PMID: 34440378Free PMC Article
Diagnosis and management of glycogen storage diseases type VI and IX: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).
Kishnani PS, Goldstein J, Austin SL, Arn P, Bachrach B, Bali DS, Chung WK, El-Gharbawy A, Brown LM, Kahler S, Pendyal S, Ross KM, Tsilianidis L, Weinstein DA, Watson MS; ACMG Work Group on Diagnosis and Management of Glycogen Storage Diseases Type VI and IX
Genet Med 2019 Apr;21(4):772-789. Epub 2019 Jan 19 doi: 10.1038/s41436-018-0364-2. PMID: 30659246

Therapy

Features of chinese patients with sitosterolemia.
Zhou Z, Su X, Cai Y, Ting TH, Zhang W, Lin Y, Xu A, Mao X, Zeng C, Liu L, Li X
Lipids Health Dis 2022 Jan 18;21(1):11. doi: 10.1186/s12944-021-01619-1. PMID: 35042526Free PMC Article
Glycogen storage disease type VI: clinical course and molecular background.
Aeppli TR, Rymen D, Allegri G, Bode PK, Häberle J
Eur J Pediatr 2020 Mar;179(3):405-413. Epub 2019 Nov 26 doi: 10.1007/s00431-019-03499-1. PMID: 31768638
Hepatic glycogen storage disorders: what have we learned in recent years?
Burda P, Hochuli M
Curr Opin Clin Nutr Metab Care 2015 Jul;18(4):415-21. doi: 10.1097/MCO.0000000000000181. PMID: 26001652
Nutrition therapy for hepatic glycogen storage diseases.
Goldberg T, Slonim AE
J Am Diet Assoc 1993 Dec;93(12):1423-30. doi: 10.1016/0002-8223(93)92246-t. PMID: 8245377
The polymorphic locus for glycogen storage disease VI (liver glycogen phosphorylase) maps to chromosome 14.
Newgard CB, Fletterick RJ, Anderson LA, Lebo RV
Am J Hum Genet 1987 Apr;40(4):351-64. PMID: 2883891Free PMC Article

Prognosis

Diagnosis and follow-up of glycogen storage disease (GSD) type VI from the largest GSD center in China.
Luo X, Duan Y, Fang D, Sun Y, Xiao B, Zhang H, Han L, Liang L, Gong Z, Gu X, Yu Y, Qiu W
Hum Mutat 2022 May;43(5):557-567. Epub 2022 Feb 24 doi: 10.1002/humu.24345. PMID: 35143115
Glycogen storage disease type VI can progress to cirrhosis: ten Chinese patients with GSD VI and a literature review.
Lu SQ, Feng JY, Liu J, Xie XB, Lu Y, Abuduxikuer K
J Pediatr Endocrinol Metab 2020 Sep 7;33(10):1321-1333. doi: 10.1515/jpem-2020-0173. PMID: 32892177
Glycogen storage disease type VI: clinical course and molecular background.
Aeppli TR, Rymen D, Allegri G, Bode PK, Häberle J
Eur J Pediatr 2020 Mar;179(3):405-413. Epub 2019 Nov 26 doi: 10.1007/s00431-019-03499-1. PMID: 31768638
Hepatic glycogen storage disorders: what have we learned in recent years?
Burda P, Hochuli M
Curr Opin Clin Nutr Metab Care 2015 Jul;18(4):415-21. doi: 10.1097/MCO.0000000000000181. PMID: 26001652
Identification of a mutation in liver glycogen phosphorylase in glycogen storage disease type VI.
Chang S, Rosenberg MJ, Morton H, Francomano CA, Biesecker LG
Hum Mol Genet 1998 May;7(5):865-70. doi: 10.1093/hmg/7.5.865. PMID: 9536091

Clinical prediction guides

Clinical and genetic spectrum of GSD type 6 in Korea.
Hahn JW, Lee H, Seong MW, Kang GH, Moon JS, Ko JS
Orphanet J Rare Dis 2023 Jun 1;18(1):132. doi: 10.1186/s13023-023-02750-1. PMID: 37264426Free PMC Article
Features of chinese patients with sitosterolemia.
Zhou Z, Su X, Cai Y, Ting TH, Zhang W, Lin Y, Xu A, Mao X, Zeng C, Liu L, Li X
Lipids Health Dis 2022 Jan 18;21(1):11. doi: 10.1186/s12944-021-01619-1. PMID: 35042526Free PMC Article
Glycogen storage disease type VI with a novel PYGL mutation: Two case reports and literature review.
Zhan Q, Lv Z, Tang Q, Huang L, Chen X, Yang M, Lan L, Shan Q
Medicine (Baltimore) 2021 Apr 23;100(16):e25520. doi: 10.1097/MD.0000000000025520. PMID: 33879691Free PMC Article
Liver histology in children with glycogen storage disorders type VI and IX.
Degrassi I, Deheragoda M, Creegen D, Mundy H, Mustafa A, Vara R, Hadzic N
Dig Liver Dis 2021 Jan;53(1):86-93. Epub 2020 Jun 4 doi: 10.1016/j.dld.2020.04.017. PMID: 32505569
Glycogen storage disease type VI: clinical course and molecular background.
Aeppli TR, Rymen D, Allegri G, Bode PK, Häberle J
Eur J Pediatr 2020 Mar;179(3):405-413. Epub 2019 Nov 26 doi: 10.1007/s00431-019-03499-1. PMID: 31768638

Recent systematic reviews

Diagnosis of hepatic glycogen storage disease patients with overlapping clinical symptoms by massively parallel sequencing: a systematic review of literature.
Beyzaei Z, Geramizadeh B, Karimzadeh S
Orphanet J Rare Dis 2020 Oct 14;15(1):286. doi: 10.1186/s13023-020-01573-8. PMID: 33054851Free PMC Article

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