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Glycogen storage disease, type I

MedGen UID:
6640
Concept ID:
C0017920
Disease or Syndrome
Synonyms: Deficiencies, Glucose-6-Phosphatase; Deficiencies, Glucosephosphatase; Deficiency, Glucose-6-Phosphatase; Deficiency, Glucosephosphatase; Disease, Gierke; Disease, Gierke's; Disease, von Gierke; Disease, von Gierke's; Gierke Disease; Gierke's Disease; Gierkes Disease; Glucose 6 Phosphatase Deficiency; Glucose-6-Phosphatase Deficiencies; Glucose-6-Phosphatase Deficiency; Glucosephosphatase Deficiencies; Glucosephosphatase Deficiency; Glycogen Storage Disease 1 (GSD I); Glycogen Storage Disease Type I; Glycogenosis 1; Hepatorenal Glycogen Storage Disease; von Gierke Disease; von Gierke's Disease; von Gierkes Disease
SNOMED CT: Glycogen storage disease, type I (7265005); Hepatorenal glycogen storage disease (7265005); von Gierke's disease (7265005); GSD I (7265005); Deficiency of glucose-6-phosphatase (124437004); Glycogen storage disease, type 1 (7265005); Liver glycogen disease (7265005); von Gierke disease (7265005)
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).
 
Related genes: SLC37A4, G6PC1
 
Monarch Initiative: MONDO:0002413
Orphanet: ORPHA364

Disease characteristics

Excerpted from the GeneReview: Glycogen Storage Disease Type I
Glycogen storage disease type I (GSD I) is characterized by accumulation of glycogen and fat in the liver and kidneys resulting in hepatomegaly and nephromegaly. Severely affected infants present in the neonatal period with severe hypoglycemia due to fasting intolerance. More commonly, untreated infants present at age three to four months with hepatomegaly, severe hypoglycemia with or without seizures, lactic acidosis, hyperuricemia, and hypertriglyceridemia. Affected children typically have doll-like faces with full cheeks, relatively thin extremities, short stature, and a protuberant abdomen. Xanthoma and diarrhea may be present. Impaired platelet function and development of reduced or dysfunctional von Willebrand factor can lead to a bleeding tendency with frequent epistaxis and menorrhagia in females. Individuals with untreated GSD Ib are more likely to develop impaired neutrophil and monocyte function as well as chronic neutropenia resulting in recurrent bacterial infections, gingivitis, periodontitis, and genital and intestinal ulcers. Long-term complications of untreated GSD I include short stature, osteoporosis, delayed puberty, renal disease (including proximal and distal renal tubular acidosis, renal stones, and kidney failure), gout, systemic hypertension, pulmonary hypertension, hepatic adenomas with potential for malignancy, pancreatitis, and polycystic ovaries. Seizures and cognitive impairment may occur in individuals with prolonged periods of hypoglycemia. Normal growth and puberty are expected in treated children. Most affected individuals live into adulthood. [from GeneReviews]
Authors:
Deeksha S Bali  |  Areeg El-Gharbawy  |  Stephanie Austin, et. al.   view full author information

Additional description

From MedlinePlus Genetics
Many people with GSDIb have a shortage of white blood cells (neutropenia), which can make them prone to recurrent bacterial infections. Neutropenia is usually apparent by age 1. Many affected individuals also have inflammation of the intestinal walls (inflammatory bowel disease). People with GSDIb may have oral problems including cavities, inflammation of the gums (gingivitis), chronic gum (periodontal) disease, abnormal tooth development, and open sores (ulcers) in the mouth. The neutropenia and oral problems are specific to people with GSDIb and are typically not seen in people with GSDIa.

Glycogen storage disease type I (also known as GSDI or von Gierke disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulation of glycogen in certain organs and tissues, especially the liver, kidneys, and small intestines, impairs their ability to function normally.

Signs and symptoms of this condition typically appear around the age of 3 or 4 months, when babies start to sleep through the night and do not eat as frequently as newborns. Affected infants may have low blood sugar (hypoglycemia), which can lead to seizures. They can also have a buildup of lactic acid in the body (lactic acidosis), high blood levels of a waste product called uric acid (hyperuricemia), and excess amounts of fats in the blood (hyperlipidemia). As they get older, children with GSDI have thin arms and legs and short stature. An enlarged liver may give the appearance of a protruding abdomen. The kidneys may also be enlarged. Affected individuals may also have diarrhea and deposits of cholesterol in the skin (xanthomas).

People with GSDI may experience delayed puberty. Beginning in young to mid-adulthood, affected individuals may have thinning of the bones (osteoporosis), a form of arthritis resulting from uric acid crystals in the joints (gout), kidney disease, and high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension). Females with this condition may also have abnormal development of the ovaries (polycystic ovaries). In affected teens and adults, tumors called adenomas may form in the liver. Adenomas are usually noncancerous (benign), but occasionally these tumors can become cancerous (malignant).

Researchers have described two types of GSDI, which differ in their signs and symptoms and genetic cause. These types are known as glycogen storage disease type Ia (GSDIa) and glycogen storage disease type Ib (GSDIb). Two other forms of GSDI have been described, and they were originally named types Ic and Id. However, these types are now known to be variations of GSDIb; for this reason, GSDIb is sometimes called GSD type I non-a.  https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-i

Term Hierarchy

Follow this link to review classifications for Glycogen storage disease, type I in Orphanet.

Professional guidelines

PubMed

Tondt J, Yancy WS, Westman EC
Nutr Res Rev 2020 Dec;33(2):260-270. Epub 2020 Feb 27 doi: 10.1017/S0954422420000050. PMID: 32102704
Kishnani PS, Austin SL, Abdenur JE, Arn P, Bali DS, Boney A, Chung WK, Dagli AI, Dale D, Koeberl D, Somers MJ, Wechsler SB, Weinstein DA, Wolfsdorf JI, Watson MS; American College of Medical Genetics and Genomics
Genet Med 2014 Nov;16(11):e1. doi: 10.1038/gim.2014.128. PMID: 25356975
Chen YT, Bazzarre CH, Lee MM, Sidbury JB, Coleman RA
Eur J Pediatr 1993;152 Suppl 1:S56-9. doi: 10.1007/BF02072090. PMID: 8319727

Recent clinical studies

Etiology

Grünert SC, Derks TGJ, Mundy H, Dalton RN, Donadieu J, Hofbauer P, Jones N, Uçar SK, LaFreniere J, Contreras EL, Pendyal S, Rossi A, Schneider B, Spiegel R, Stepien KM, Wesol-Kucharska D, Veiga-da-Cunha M, Wortmann SB
Mol Genet Metab 2024 Mar;141(3):108144. Epub 2024 Jan 17 doi: 10.1016/j.ymgme.2024.108144. PMID: 38277989
Hannah WB, Derks TGJ, Drumm ML, Grünert SC, Kishnani PS, Vissing J
Nat Rev Dis Primers 2023 Sep 7;9(1):46. doi: 10.1038/s41572-023-00456-z. PMID: 37679331
Derks TGJ, Rodriguez-Buritica DF, Ahmad A, de Boer F, Couce ML, Grünert SC, Labrune P, López Maldonado N, Fischinger Moura de Souza C, Riba-Wolman R, Rossi A, Saavedra H, Gupta RN, Valayannopoulos V, Mitchell J
Nutrients 2021 Oct 27;13(11) doi: 10.3390/nu13113828. PMID: 34836082Free PMC Article
Kishnani PS, Austin SL, Abdenur JE, Arn P, Bali DS, Boney A, Chung WK, Dagli AI, Dale D, Koeberl D, Somers MJ, Wechsler SB, Weinstein DA, Wolfsdorf JI, Watson MS; American College of Medical Genetics and Genomics
Genet Med 2014 Nov;16(11):e1. doi: 10.1038/gim.2014.128. PMID: 25356975
Froissart R, Piraud M, Boudjemline AM, Vianey-Saban C, Petit F, Hubert-Buron A, Eberschweiler PT, Gajdos V, Labrune P
Orphanet J Rare Dis 2011 May 20;6:27. doi: 10.1186/1750-1172-6-27. PMID: 21599942Free PMC Article

Diagnosis

Hannah WB, Derks TGJ, Drumm ML, Grünert SC, Kishnani PS, Vissing J
Nat Rev Dis Primers 2023 Sep 7;9(1):46. doi: 10.1038/s41572-023-00456-z. PMID: 37679331
Massese M, Tagliaferri F, Dionisi-Vici C, Maiorana A
Orphanet J Rare Dis 2022 Jun 20;17(1):241. doi: 10.1186/s13023-022-02387-6. PMID: 35725468Free PMC Article
Marion RW, Paljevic E
Pediatr Rev 2020 Jan;41(1):41-44. doi: 10.1542/pir.2018-0146. PMID: 31894075
Kishnani PS, Austin SL, Abdenur JE, Arn P, Bali DS, Boney A, Chung WK, Dagli AI, Dale D, Koeberl D, Somers MJ, Wechsler SB, Weinstein DA, Wolfsdorf JI, Watson MS; American College of Medical Genetics and Genomics
Genet Med 2014 Nov;16(11):e1. doi: 10.1038/gim.2014.128. PMID: 25356975
Froissart R, Piraud M, Boudjemline AM, Vianey-Saban C, Petit F, Hubert-Buron A, Eberschweiler PT, Gajdos V, Labrune P
Orphanet J Rare Dis 2011 May 20;6:27. doi: 10.1186/1750-1172-6-27. PMID: 21599942Free PMC Article

Therapy

Derks TGJ, Rodriguez-Buritica DF, Ahmad A, de Boer F, Couce ML, Grünert SC, Labrune P, López Maldonado N, Fischinger Moura de Souza C, Riba-Wolman R, Rossi A, Saavedra H, Gupta RN, Valayannopoulos V, Mitchell J
Nutrients 2021 Oct 27;13(11) doi: 10.3390/nu13113828. PMID: 34836082Free PMC Article
Chou JY, Jun HS, Mansfield BC
J Inherit Metab Dis 2015 May;38(3):511-9. Epub 2014 Oct 7 doi: 10.1007/s10545-014-9772-x. PMID: 25288127
Christensen RD, Calhoun DA
Clin Perinatol 2004 Mar;31(1):29-38. doi: 10.1016/j.clp.2004.03.011. PMID: 15183654
Kannourakis G
Semin Hematol 2002 Apr;39(2):103-6. doi: 10.1053/shem.2002.31920. PMID: 11957192
Lloyd JK
Br Heart J 1975 Feb;37(2):105-14. doi: 10.1136/hrt.37.2.105. PMID: 164201Free PMC Article

Prognosis

Hannah WB, Derks TGJ, Drumm ML, Grünert SC, Kishnani PS, Vissing J
Nat Rev Dis Primers 2023 Sep 7;9(1):46. doi: 10.1038/s41572-023-00456-z. PMID: 37679331
Massese M, Tagliaferri F, Dionisi-Vici C, Maiorana A
Orphanet J Rare Dis 2022 Jun 20;17(1):241. doi: 10.1186/s13023-022-02387-6. PMID: 35725468Free PMC Article
Derks TGJ, Rodriguez-Buritica DF, Ahmad A, de Boer F, Couce ML, Grünert SC, Labrune P, López Maldonado N, Fischinger Moura de Souza C, Riba-Wolman R, Rossi A, Saavedra H, Gupta RN, Valayannopoulos V, Mitchell J
Nutrients 2021 Oct 27;13(11) doi: 10.3390/nu13113828. PMID: 34836082Free PMC Article
Froissart R, Piraud M, Boudjemline AM, Vianey-Saban C, Petit F, Hubert-Buron A, Eberschweiler PT, Gajdos V, Labrune P
Orphanet J Rare Dis 2011 May 20;6:27. doi: 10.1186/1750-1172-6-27. PMID: 21599942Free PMC Article
Saborio P, Scheinman J
Curr Opin Pediatr 1998 Apr;10(2):174-83. doi: 10.1097/00008480-199804000-00011. PMID: 9608896

Clinical prediction guides

Vai S, Falchetti A, Corbetta S, Bianchi ML, Alberio C, Carrara S, Gasperini S, Pretese R, Parisi L, Teti A, Maurizi A
Calcif Tissue Int 2024 Nov;115(5):661-672. Epub 2024 Oct 25 doi: 10.1007/s00223-024-01302-4. PMID: 39453459Free PMC Article
Lan J, Zhang Y, Jin C, Chen H, Su Z, Wu J, Ma N, Zhang X, Lu Y, Chen Y, Zeng X, Zhang H, Zheng G, Sun Y, Wang C, Hu Y, Wang Y, Liu Y, Zeng Z, Shi L, He J, Cao A, Wang Y, Pan X, Jin G, Wang Y, Jiang X, Shen H, Tang Q, Xie X, Xiao Y, Zhong X, Zhang X, Zeng L, Ye L, Xie J, Geng L, Li Z, Wu X, Wang Y, Mao R, Zhang S, Huang S, Liu S, Zeng H, Xu W, Gong S, Guo Y, Yang M
Adv Sci (Weinh) 2024 Aug;11(30):e2309471. Epub 2024 Jun 18 doi: 10.1002/advs.202309471. PMID: 38889269Free PMC Article
Muzetti JH, do Valle DA, Santos MLSF, Telles BA, Cordeiro ML
Front Endocrinol (Lausanne) 2021;12:685272. Epub 2021 May 21 doi: 10.3389/fendo.2021.685272. PMID: 34093448Free PMC Article
Kannourakis G
Semin Hematol 2002 Apr;39(2):103-6. doi: 10.1053/shem.2002.31920. PMID: 11957192
Chen YT, Bazzarre CH, Lee MM, Sidbury JB, Coleman RA
Eur J Pediatr 1993;152 Suppl 1:S56-9. doi: 10.1007/BF02072090. PMID: 8319727

Recent systematic reviews

Zelei T, Kovács S, Finn P, Nagy D, Sikirica V, Carlson KB, Vokó Z
J Pediatr Endocrinol Metab 2023 Sep 26;36(9):809-817. Epub 2023 Aug 25 doi: 10.1515/jpem-2023-0127. PMID: 37615591
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
Shah KK, O'Dell SD
J Hum Nutr Diet 2013 Aug;26(4):329-39. Epub 2013 Jan 7 doi: 10.1111/jhn.12030. PMID: 23294025

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