Glycogen storage disease due to glucose-6-phosphatase deficiency type a

General Information (adopted from Orphanet):

Synonyms, Signs: GSD1A
GSD1

Glycogenosis due to glucose-6-phosphatase deficiency type a
Hepatorenal form of glycogen storage disease
GSD due to G6P deficiency type a
Hepatorenal glycogenosis
von Gierke disease
GSD type 1a
Glucose-6-phosphatase deficiency
Glycogen storage disease due to G6P deficiency type a
Glycogen storage disease type 1a
Glycogenosis type Ia
G6P deficiency type a
Glycogen storage disease I
GSDIa
GSD Ia
Number of Symptoms 51
OrphanetNr: 79258
OMIM Id: 232200
ICD-10: E74.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance:
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Glycogen storage disease due to glucose-6-phosphatase deficiency
 -Rare genetic disease
 -Rare hepatic disease
 -Rare renal disease

Comment:

GSD-Ia is caused by a deficiency in the liver/kidney/intestine-restricted G6Pase-alpha (G6PC) while GSD-Ib is caused by a deficiency in the ubiquitously expressed G6PT (or SLC37A4) (PMID:25288127). A new framework has now emerged which shows that the G6PT/G6Pase-α complex (GSD-Ia) maintains interprandial glucose homeostasis whereas the G6PT/G6Pase-β complex (GSD-Ib) maintains neutrophil homeostasis and function (PMID:20975743). Eighty-nine separate G6PC mutations, including 58 missense, ten nonsense, 17 insertion/deletion, three splicing and one no-stop mutation have been identified to date (PMID:25288127).

Symptom Information: Sort by abundance 

1
(HPO:0003537) Hypouricemia 16176880 IBIS 13 / 7739
2
(HPO:0000093) Proteinuria 20975743 IBIS 169 / 7739
3
(HPO:0000105) Enlarged kidneys 25288127 IBIS 30 / 7739
4
(HPO:0000787) Nephrolithiasis 12373567 IBIS 78 / 7739
5
(HPO:0012594) Microalbuminuria 12373567 IBIS 6 / 7739
6
(HPO:0000132) Menorrhagia 24201678 IBIS 40 / 7739
7
(HPO:0000121) Nephrocalcinosis 12373567 IBIS 57 / 7739
8
(HPO:0000083) Renal insufficiency 20975743 IBIS 232 / 7739
9
(HPO:0000097) Focal segmental glomerulosclerosis 3422104; 19808227 IBIS 37 / 7739
10
(HPO:0012212) Abnormal glomerular filtration rate 17410288 IBIS 4 / 7739
11
(HPO:0000421) Epistaxis 12373567 IBIS 85 / 7739
12
(HPO:0000295) Doll-like facies 12373567 IBIS 5 / 7739
13
(HPO:0000660) Lipemia retinalis 7746653 IBIS 7 / 7739
14
(HPO:0002197) Generalized seizures 12373567 IBIS 30 / 7739
15
(HPO:0001249) Intellectual disability 12373567 IBIS 1089 / 7739
16
(HPO:0001259) Coma 12373567 IBIS 65 / 7739
17
(HPO:0000823) Delayed puberty 12373567 IBIS 65 / 7739
18
(HPO:0000938) Osteopenia 20975743 IBIS 138 / 7739
19
(HPO:0002750) Delayed skeletal maturation 12373567 IBIS 250 / 7739
20
(HPO:0000939) Osteoporosis 25288127 IBIS 129 / 7739
21
(HPO:0001997) Gout 25288127 IBIS 18 / 7739
22
(HPO:0002240) Hepatomegaly 12373567 IBIS 467 / 7739
23
(HPO:0002910) Elevated hepatic transaminases 17410288 IBIS 158 / 7739
24
(HPO:0001733) Pancreatitis 12373567 IBIS 46 / 7739
25
(HPO:0001744) Splenomegaly 12373567 IBIS 337 / 7739
26
(HPO:0001402) Hepatocellular carcinoma 25288127 IBIS 25 / 7739
27
(HPO:0001538) Protuberant abdomen 12373567 IBIS 36 / 7739
28
(HPO:0002013) Vomiting 12373567 IBIS 191 / 7739
29
(HPO:0012028) Hepatocellular adenoma 12373567 IBIS 6 / 7739
30
(HPO:0002014) Diarrhea 12373567 IBIS 225 / 7739
31
(HPO:0004322) Short stature 20975743 IBIS 1232 / 7739
32
(HPO:0001508) Failure to thrive 12373567 IBIS 454 / 7739
33
(HPO:0001510) Growth delay 12373567 IBIS 295 / 7739
34
(HPO:0000975) Hyperhidrosis 12373567 IBIS 64 / 7739
35
(HPO:0000980) Pallor 12373567 IBIS 52 / 7739
36
(HPO:0000991) Xanthomatosis 12846528 IBIS 16 / 7739
37
(HPO:0002092) Pulmonary hypertension 25288127 IBIS 109 / 7739
38
(HPO:0000822) Hypertension 25288127 IBIS 224 / 7739
39
(HPO:0001903) Anemia 12373567 IBIS 289 / 7739
40
(HPO:0001928) Abnormality of coagulation 3087438; 16435187 IBIS 44 / 7739
41
(HPO:0001892) Abnormal bleeding 12373567 IBIS 85 / 7739
42
(HPO:0003010) Prolonged bleeding time 12373567 IBIS 88 / 7739
43
(HPO:0003124) Hypercholesterolemia 25288127 IBIS 53 / 7739
44
(HPO:0003077) Hyperlipidemia 25288127 IBIS 37 / 7739
45
(HPO:0003128) Lactic acidosis 25288127 IBIS 116 / 7739
46
(HPO:0011014) Abnormal glucose homeostasis Very frequent [IBIS] 25288127 IBIS 5 / 7739
47
(HPO:0002155) Hypertriglyceridemia 25288127 IBIS 67 / 7739
48
(HPO:0001943) Hypoglycemia Very frequent [IBIS] 25288127 IBIS 131 / 7739
49
(HPO:0002149) Hyperuricemia 12373567 IBIS 37 / 7739
50
(HPO:0003199) Decreased muscle mass 19808227 IBIS 27 / 7739
51
(OMIM) Liver transaminases normal to slightly increased 17410288 IBIS 2 / 7739

Associated genes:

G6PC;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Glycogen storage disease type I (GSD1a), also known as von Gierke disease, typically manifests during the first year of life with severe hypoglycemia and hepatomegaly caused by the accumulation of glycogen. Affected individuals exhibit growth retardation, delayed puberty, lactic ...
Diagnosis OMIM Seydewitz and Matern (2000) achieved 100% mutation detection rate in a study of 40 patients with GSD Ia. They identified 5 novel mutations in the G6PC gene. The authors suggested that molecular genetic analysis is a reliable and convenient ...
Clinical Description OMIM Burchell et al. (1987) reported 2 women, aged 51 and 22 years, with partial GSD type Ia, and a 54-year-old man with complete GSD type Ia. The patient with complete type Ia had had unexplained hepatomegaly and a bleeding ...
Molecular genetics OMIM In 2 patients with glycogen storage disease Ia, Lei et al. (1993) identified homozygous and compound heterozygous mutations, respectively, in the G6PC gene (613742.0001-613742.0003).

Lei et al. (1995) used SSCP analysis and DNA sequencing to characterize the ...

Population genetics OMIM Lei et al. (1993) stated that glycogen storage disease Ia has an incidence of 1 in 100,000 to 300,000.

Ekstein et al. (2004) found that the prevalence of GSD Ia in the Ashkenazi Jewish population is 1 ...