Glycogen storage disease type III

Signs and symptoms

Glycogen storage disease type III presents during infancy with hypoglycemia and failure to thrive. Clinical examination usually reveals hepatomegaly. Muscular disease, including hypotonia and cardiomyopathy, usually occurs later. The liver pathology typically regresses as the individual enters adolescence, as does splenomegaly, should the individual develop it.

Genetics

In regards to genetics glycogen storage disease type III is inherited in an autosomal recessive pattern (which means both parents need to be a carrier), and occurs in about 1 of every 100,000 live births. The highest incidence of glycogen storage disease type III is in the Faroe Islands where it occurs in 1 out of every 3,600 births, probably due to a founder effect.

There seem to be two mutations in exon 3 (c.17_18delAG) being one of them, which are linked to the subtype IIIb.

The amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase gene and its mutations, are at the root of this condition. The gene is responsible for creating glycogen debranching enzyme, which in turn helps in glycogen decomposition.

Diagnosis

In terms of the diagnosis of glycogen storage disease type III, the following tests/exams are carried out to determine if the individual has the condition:

• Biopsy (muscle or liver)
• CBC
• Ultrasound
• DNA mutation analysis (helps ascertain GSD III subtype)

Differential diagnosis

The differential diagnosis of glycogen storage disease type III includes GSD I, GSD IX and GSD VI. This however does not mean other glycogen storage diseases should not be distinguished as well.

Classification

Clinical manifestations of glycogen storage disease type III are divided into four classes:

• GSD IIIa, is the most common, (along with GSD IIIb) and clinically includes muscle and liver involvement
• GSD IIIb, which clinically has liver involvement but no muscle involvement
• GSD IIIc which clinically affects liver and muscle.
• GSD IV affects the liver only (not muscle)

Treatment

thumb|180 px|Glucose Treatment for glycogen storage disease type III may involve a high-protein diet, to facilitate gluconeogenesis. Additionally the individual may need:

• IV glucose (if oral route is inadvisable)
• Nutritional specialist
• Vitamin D (for osteoporosis/secondary complication)
• Hepatic transplant (if a complication occurs)

References

References

1. "Glycogen storage disease type 3 {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program".
2. Reference, Genetics Home. "glycogen storage disease type III".
3. J. G. Salway. (2012). "Medical Biochemistry at a Glance". John Wiley & Sons.
4. "Genetics of Glycogen-Storage Disease Type III Clinical Presentation: History, Physical, Causes".
5. (May 2001). "Molecular genetic basis and prevalence of glycogen storage disease type IIIA in the Faroe Islands". European Journal of Human Genetics.
6. "OMIM Entry - # 232400 - Glycogen Storage Disease III; GSD3".
7. Reference, Genetics Home. "AGL".
8. "Glycogen Storage Disorders. Inborn errors of metabolism {{!}} Patient".
9. (1 July 2010). "Glycogen Storage Disease Type III diagnosis and management guidelines". Genetics in Medicine.
10. (1 January 1993). "Glycogen Storage Disease Type III". GeneReviews.