– Glycogen Storage Disease Type Ia – GSD Ia (G6PC gene) – Also known as: von Gierke disease; Hepatorenal form of glycogen storage disease; Glucose-6-phosphatase deficiency; Hepatorenal glycogenosis; GSDIa – OMIM#232200

 – Glycogen Storage Disease Type Ib – GSD Ib (SLC37A4 gene) – Also known as: glucose-6-phosphate transport defect; GSDIb – OMIM#232220

– Glycogen Storage Disease Type Ic – GSD Ic (SLC37A4 gene) OMIM#232240

Glycogen Storage Disease Type III – GSD III (AGL gene) – Also known as: Forbes disease; Cori Disease; Limit dextrinosis; Amylo-1-6-glucosidase deficiency; AGL deficiency; Glycogen Debrancher deficiency; GDE deficiency – GSDIIIa/b/c – OMIM#232400

– Glycogen Storage Disease Type VI – GSD VI (PYGL gene) – Also known as: Hers disease; Phosphorylase deficiency glycogen-storage disease of liver – GSD VI – OMIM#232700

– Glycogen Storage Disease Type IXa – GSD IXa (PHKA2 gene) Also known as: Liver Glycogenosis, X-Linked, Type I (XLG1); Glycogen Storage Disease VIII; GSD VIII; GSD8, Formerly – OMIM#306000

– Glycogen Storage Disease Type IXb – GSD IXb (PHKB gene) Also known as: Glycogenosis of Liver and Muscle, autosomal recessive; Phosphorylase kinase deficiency of Liver and Muscle, autosomal recessive – OMIM#261750

– Glycogen Storage Disease Type IXc – GSD IXc (PHKG2 gene) OMIM#613027

1. The Disease:

Glycogen storage disorders (GSDs) are a group of rare metabolic diseases with abnormal glycogen metabolism. The incidence of GSD is approximately 1:10,000 live births. These groups of diseases are caused by various enzyme deficiencies resulting in abnormal glycogen synthesis, or glycolysis, typically within the muscles and/or liver cells. Different types of GSDs are categorized based on the type of deficient enzymes and affected tissues. GSDs with liver involvement (Hepatic GSDs) are a complex group of disorders, including 8 diseases named above.

2. The Symptoms:

All of them are associated with hypoglycaemia (low blood sugar) and hepatomegaly (enlargement of the liver). Clinical signs of different types of hepatic GSDs are very similar, such as short fasting intervals (less than 4 h), hepatomegaly or hypoglycemia, which can be observed in GSD type I as well as GSD III, IV, VI and IX. However, treatment methods and modalities, complications, and natural histories are different in various types of GSDs, which shows the importance of knowing early the definitive diagnosis as proposed on BabyDetect. To see specific clinical findings and treatment, talk to your metabolic doctor, clinical geneticist, child hepatologist or read additional information below.

3. Actions to take in case of early diagnosis:

  • Infants with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in any of the genes above, except PHKA2 gene which is X linked, so a hemizygous pathogenic variant is sufficient) should continue breastfeeding, avoid fasting. Early treatment is essential in preventing chronic symptoms.
  • Genetic results are replacing the liver biopsy, due to the invasive characteristic of test.
  • Hepatic GSDs are lifelong diseases that require regular evaluation by a metabolic physician and metabolic nutritionist to avoid fasting, and follow a diet high in complex carbohydrates and protein to prevent hypoglycemia and ketosis.
  • Patients with GSD Ib/Ic may need to follow a different vaccination program and should also be followed by a child haematologist due to immune deficiency and blood cells abnormalities.
  • Monitoring of blood glucose concentration and blood ketones routinely as well as during times of stress (e.g., illness, intense activity, rapid growth, puberty and reduced food intake). In children younger than age 18 years, liver ultrasound examination should be performed every 12 to 24 months. With increasing age, CT or MRI using intravenous contrast should be considered to evaluate for complications of liver disease.
  • Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. For more information