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Glycogen storage disease type III(GSD3)

MedGen UID:
6641
Concept ID:
C0017922
Disease or Syndrome
Synonyms: Amylo-1,6-glucosidase deficiency; Cori disease; Forbes disease; Glycogen debrancher deficiency; Glycogen storage disease type 3; GSD3; Limit dextrinosis
SNOMED CT: Glycogen storage disease, type III (66937008); Cori's disease (66937008); Amylo-1,6-glucosidase deficiency (66937008); Debrancher deficiency glycogen storage disease (66937008); Limit dextrinosis (66937008); GSD III (66937008); Glycogen storage disease type 3 (66937008); Cori disease (66937008); Debrancher enzyme deficiency (66937008); Limit dextrin - glycogen (66937008); Glycogen storage disease type III (66937008)
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).
 
Gene (location): AGL (1p21.2)
 
Monarch Initiative: MONDO:0009291
OMIM®: 232400
Orphanet: ORPHA366

Disease characteristics

Excerpted from the GeneReview: Glycogen Storage Disease Type III
Glycogen storage disease type III (GSD III) is characterized by variable liver, cardiac muscle, and skeletal muscle involvement. GSD IIIa is the most common subtype, present in about 85% of affected individuals; it manifests with liver and muscle involvement. GSD IIIb, with liver involvement only, comprises about 15% of all affected individuals. In infancy and early childhood, liver involvement presents as hepatomegaly and failure to thrive, with fasting ketotic hypoglycemia, hyperlipidemia, and elevated hepatic transaminases. In adolescence and adulthood, liver disease becomes less prominent. Most individuals develop cardiac involvement with cardiac hypertrophy and/or cardiomyopathy. Skeletal myopathy manifesting as weakness may be evident in childhood and slowly progresses, typically becoming prominent in the third to fourth decade. The overall prognosis is favorable but cannot be predicted on an individual basis. Long-term complications such as muscular and cardiac symptoms as well as liver fibrosis/cirrhosis and hepatocellular carcinoma may have a severe impact on prognosis and quality of life. To date, it is unknown if long-term complications can be alleviated and/or avoided by dietary interventions. [from GeneReviews]
Authors:
Andrea B Schreuder  |  Alessandro Rossi  |  Sarah C Grünert, et. al.   view full author information

Additional descriptions

From OMIM
Glycogen storage disease III is an autosomal recessive metabolic disorder caused by deficiency of the glycogen debrancher enzyme and associated with an accumulation of abnormal glycogen with short outer chains. Most patients are enzyme-deficient in both liver and muscle (IIIa), but about 15% are enzyme-deficient in liver only (IIIb) (Shen et al., 1996). These subtypes have been explained by differences in tissue expression of the deficient enzyme (Endo et al., 2006). In rare cases, selective loss of only 1 of the 2 debranching activities, glucosidase or transferase, results in type IIIc or IIId, respectively. (Van Hoof and Hers, 1967; Ding et al., 1990). Clinically, patients with GSD III present in infancy or early childhood with hepatomegaly, hypoglycemia, and growth retardation. Muscle weakness in those with IIIa is minimal in childhood but can become more severe in adults; some patients develop cardiomyopathy (Shen et al., 1996). Lucchiari et al. (2007) provided a review of GSD III.  http://www.omim.org/entry/232400
From MedlinePlus Genetics
Glycogen storage disease type III (also known as GSDIII or Cori disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulated glycogen is structurally abnormal and impairs the function of certain organs and tissues, especially the liver and muscles.

GSDIII is divided into types IIIa, IIIb, IIIc, and IIId, which are distinguished by their pattern of signs and symptoms. GSD types IIIa and IIIc mainly affect the liver and muscles, and GSD types IIIb and IIId typically affect only the liver. It is very difficult to distinguish between the types of GSDIII that affect the same tissues. GSD types IIIa and IIIb are the most common forms of this condition.

Beginning in infancy, individuals with any type of GSDIII may have low blood glucose (hypoglycemia), excess amounts of fats in the blood (hyperlipidemia), and elevated blood levels of liver enzymes. As they get older, children with this condition typically develop an enlarged liver (hepatomegaly). Liver size usually returns to normal during adolescence, but some affected individuals develop chronic liver disease (cirrhosis) and liver failure later in life. People with GSDIII often have slow growth because of their liver problems, which can lead to short stature. In a small percentage of people with GSDIII, noncancerous (benign) tumors called adenomas may form in the liver.

Individuals with GSDIIIa may develop muscle weakness (myopathy) later in life. These muscle problems can affect both heart (cardiac) muscle and the muscles that are used for movement (skeletal muscles). Muscle involvement varies greatly among affected individuals. The first signs and symptoms are typically poor muscle tone (hypotonia) and mild myopathy in early childhood. The myopathy may become severe by early to mid-adulthood. Some people with GSDIIIa have a weakened heart muscle (cardiomyopathy), but affected individuals usually do not experience heart failure. Other people affected with GSDIIIa have no cardiac muscle problems.  https://medlineplus.gov/genetics/condition/glycogen-storage-disease-type-iii

Clinical features

From HPO
Ventricular hypertrophy
MedGen UID:
87400
Concept ID:
C0340279
Disease or Syndrome
Enlargement of the cardiac ventricular muscle tissue with increase in the width of the wall of the ventricle and loss of elasticity. Ventricular hypertrophy is clinically differentiated into left and right ventricular hypertrophy.
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Hyperlipidemia
MedGen UID:
5692
Concept ID:
C0020473
Disease or Syndrome
An elevated lipid concentration in the blood.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Elevated hepatic transaminase
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.
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Increase in width of the nasal tip.
Thin vermilion border
MedGen UID:
108294
Concept ID:
C0578038
Finding
Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips).
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Deeply set eye
MedGen UID:
473112
Concept ID:
C0423224
Finding
An eye that is more deeply recessed into the plane of the face than is typical.

Term Hierarchy

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

Professional guidelines

PubMed

Wicker C, Cano A, Decostre V, Froissart R, Maillot F, Perry A, Petit F, Voillot C, Wahbi K, Wenz J, Laforêt P, Labrune P
Eur J Med Res 2023 Jul 24;28(1):253. doi: 10.1186/s40001-023-01212-5. PMID: 37488624Free PMC Article
Derks TG, Smit GP
J Inherit Metab Dis 2015 May;38(3):545-50. Epub 2014 Aug 28 doi: 10.1007/s10545-014-9756-x. PMID: 25164784
Kishnani PS, Austin SL, Arn P, Bali DS, Boney A, Case LE, Chung WK, Desai DM, El-Gharbawy A, Haller R, Smit GP, Smith AD, Hobson-Webb LD, Wechsler SB, Weinstein DA, Watson MS; ACMG
Genet Med 2010 Jul;12(7):446-63. doi: 10.1097/GIM.0b013e3181e655b6. PMID: 20631546

Recent clinical studies

Etiology

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
Hennis PJ, Murphy E, Meijer RI, Lachmann RH, Ramachandran R, Bordoli C, Rayat G, Tomlinson DJ
Orphanet J Rare Dis 2022 Jan 31;17(1):28. doi: 10.1186/s13023-022-02184-1. PMID: 35101075Free PMC Article
Sentner CP, Hoogeveen IJ, Weinstein DA, Santer R, Murphy E, McKiernan PJ, Steuerwald U, Beauchamp NJ, Taybert J, Laforêt P, Petit FM, Hubert A, Labrune P, Smit GPA, Derks TGJ
J Inherit Metab Dis 2016 Sep;39(5):697-704. Epub 2016 Apr 22 doi: 10.1007/s10545-016-9932-2. PMID: 27106217Free PMC Article
Burda P, Hochuli M
Curr Opin Clin Nutr Metab Care 2015 Jul;18(4):415-21. doi: 10.1097/MCO.0000000000000181. PMID: 26001652
Kishnani PS, Austin SL, Arn P, Bali DS, Boney A, Case LE, Chung WK, Desai DM, El-Gharbawy A, Haller R, Smit GP, Smith AD, Hobson-Webb LD, Wechsler SB, Weinstein DA, Watson MS; ACMG
Genet Med 2010 Jul;12(7):446-63. doi: 10.1097/GIM.0b013e3181e655b6. PMID: 20631546

Diagnosis

Wicker C, Cano A, Decostre V, Froissart R, Maillot F, Perry A, Petit F, Voillot C, Wahbi K, Wenz J, Laforêt P, Labrune P
Eur J Med Res 2023 Jul 24;28(1):253. doi: 10.1186/s40001-023-01212-5. PMID: 37488624Free PMC Article
Sadeh M, Yosovich K, Dabby R
J Clin Neuromuscul Dis 2021 Jun 1;22(4):224-227. doi: 10.1097/CND.0000000000000339. PMID: 34019008
Berling É, Laforêt P, Wahbi K, Labrune P, Petit F, Ronzitti G, O'Brien A
J Inherit Metab Dis 2021 May;44(3):521-533. Epub 2021 Jan 3 doi: 10.1002/jimd.12355. PMID: 33368379
Sentner CP, Hoogeveen IJ, Weinstein DA, Santer R, Murphy E, McKiernan PJ, Steuerwald U, Beauchamp NJ, Taybert J, Laforêt P, Petit FM, Hubert A, Labrune P, Smit GPA, Derks TGJ
J Inherit Metab Dis 2016 Sep;39(5):697-704. Epub 2016 Apr 22 doi: 10.1007/s10545-016-9932-2. PMID: 27106217Free PMC Article
Kishnani PS, Austin SL, Arn P, Bali DS, Boney A, Case LE, Chung WK, Desai DM, El-Gharbawy A, Haller R, Smit GP, Smith AD, Hobson-Webb LD, Wechsler SB, Weinstein DA, Watson MS; ACMG
Genet Med 2010 Jul;12(7):446-63. doi: 10.1097/GIM.0b013e3181e655b6. PMID: 20631546

Therapy

Jauze L, Monteillet L, Mithieux G, Rajas F, Ronzitti G
Hum Gene Ther 2019 Oct;30(10):1263-1273. Epub 2019 Aug 27 doi: 10.1089/hum.2019.102. PMID: 31319709
Burda P, Hochuli M
Curr Opin Clin Nutr Metab Care 2015 Jul;18(4):415-21. doi: 10.1097/MCO.0000000000000181. PMID: 26001652
Derks TG, Smit GP
J Inherit Metab Dis 2015 May;38(3):545-50. Epub 2014 Aug 28 doi: 10.1007/s10545-014-9756-x. PMID: 25164784
Hershkovitz E, Donald A, Mullen M, Lee PJ, Leonard JV
J Inherit Metab Dis 1999 Dec;22(8):891-8. doi: 10.1023/a:1005687323096. PMID: 10604141
Goldberg T, Slonim AE
J Am Diet Assoc 1993 Dec;93(12):1423-30. doi: 10.1016/0002-8223(93)92246-t. PMID: 8245377

Prognosis

Wicker C, Cano A, Decostre V, Froissart R, Maillot F, Perry A, Petit F, Voillot C, Wahbi K, Wenz J, Laforêt P, Labrune P
Eur J Med Res 2023 Jul 24;28(1):253. doi: 10.1186/s40001-023-01212-5. PMID: 37488624Free PMC Article
Burda P, Hochuli M
Curr Opin Clin Nutr Metab Care 2015 Jul;18(4):415-21. doi: 10.1097/MCO.0000000000000181. PMID: 26001652
Kishnani PS, Austin SL, Arn P, Bali DS, Boney A, Case LE, Chung WK, Desai DM, El-Gharbawy A, Haller R, Smit GP, Smith AD, Hobson-Webb LD, Wechsler SB, Weinstein DA, Watson MS; ACMG
Genet Med 2010 Jul;12(7):446-63. doi: 10.1097/GIM.0b013e3181e655b6. PMID: 20631546
Matern D, Starzl TE, Arnaout W, Barnard J, Bynon JS, Dhawan A, Emond J, Haagsma EB, Hug G, Lachaux A, Smit GP, Chen YT
Eur J Pediatr 1999 Dec;158 Suppl 2(Suppl 2):S43-8. doi: 10.1007/pl00014320. PMID: 10603098Free PMC Article
Greene HL
Semin Liver Dis 1982 Nov;2(4):291-301. doi: 10.1055/s-2008-1040716. PMID: 6763342

Clinical prediction guides

Wicker C, Cano A, Decostre V, Froissart R, Maillot F, Perry A, Petit F, Voillot C, Wahbi K, Wenz J, Laforêt P, Labrune P
Eur J Med Res 2023 Jul 24;28(1):253. doi: 10.1186/s40001-023-01212-5. PMID: 37488624Free PMC Article
Hennis PJ, Murphy E, Meijer RI, Lachmann RH, Ramachandran R, Bordoli C, Rayat G, Tomlinson DJ
Orphanet J Rare Dis 2022 Jan 31;17(1):28. doi: 10.1186/s13023-022-02184-1. PMID: 35101075Free PMC Article
Jauze L, Monteillet L, Mithieux G, Rajas F, Ronzitti G
Hum Gene Ther 2019 Oct;30(10):1263-1273. Epub 2019 Aug 27 doi: 10.1089/hum.2019.102. PMID: 31319709
Sentner CP, Hoogeveen IJ, Weinstein DA, Santer R, Murphy E, McKiernan PJ, Steuerwald U, Beauchamp NJ, Taybert J, Laforêt P, Petit FM, Hubert A, Labrune P, Smit GPA, Derks TGJ
J Inherit Metab Dis 2016 Sep;39(5):697-704. Epub 2016 Apr 22 doi: 10.1007/s10545-016-9932-2. PMID: 27106217Free PMC Article
Hershkovitz E, Forschner I, Mandel H, Spiegel R, Lerman-Sagie T, Anikster Y, Zeharia A, Moses S
Pediatr Endocrinol Rev 2014 Mar;11(3):318-23. PMID: 24716397

Recent systematic reviews

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
Rossi A, Hoogeveen IJ, Bastek VB, de Boer F, Montanari C, Meyer U, Maiorana A, Bordugo A, Dianin A, Campana C, Rigoldi M, Kishnani PS, Pendyal S, Strisciuglio P, Gasperini S, Parenti G, Parini R, Paci S, Melis D, Derks TGJ
J Inherit Metab Dis 2020 Jul;43(4):770-777. Epub 2020 Feb 26 doi: 10.1002/jimd.12224. PMID: 32064649Free PMC Article
Demo E, Frush D, Gottfried M, Koepke J, Boney A, Bali D, Chen YT, Kishnani PS
J Hepatol 2007 Mar;46(3):492-8. Epub 2006 Nov 9 doi: 10.1016/j.jhep.2006.09.022. PMID: 17196294Free PMC Article

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