MEN (General Swiss-German Mennonite)

Inheritance: autosomal recessive
Genes: PYGL

GSD VI
GSD6
HERS disease
PYGL
Glycogen phosphorylase deficiency
Glycogen storage disease of the liver

Low blood sugar
Hypoglycemia
Electrolyte imbalance
Ketosis
Growth retardation
Enlarged liver
Hepatomegaly
Fatique
Irritability

Glycogen Storage Disease VI

Clinical Characteristics

General description (for patients):

Glycogen storage disease of the liver is caused by a mutation that results in defective sugar metabolism. Young children exhibit slow growth and have enlarged livers in the first year of life. Lack of energy, irritability, and abnormal sweating are all symptoms that result from a low blood sugar. This type of glycogen disease is relatively mild. While a biopsy of the liver gives diagnostic information, it is also possible to determine the cause by a test for the gene in blood and saliva.

Medical description:  

A number of glycogen storage diseases have been identified secondary to phosphorylase deficiencies in muscle, liver, and brain. Type VI, found in the Mennonite population of Eastern Pennsylvania, has a relatively mild phenotype with accumulation of glycogen primarily in the liver. The inability to release glucose from stored hepatic glycogen results in hypoglycemia and the clinical picture of fatigue, irritability, abnormal sweating, and decelerating linear growth. Cardiac and skeletal muscles are not affected. Ketosis with elevated levels of triglycerides and cholesterol can result. Symptoms tend to decrease as individuals grow. Liver biopsies show diagnostic changes of excessive glycogen storage although genotyping is less invasive and is more precise diagnostically.

Genetics:

Glycogen storage diseases are autosomal recessive disorders secondary to phosphorylase enzyme deficiencies. Many allelic variants are known, of which one in the PYGL locus (IVS13+1G>A) on chromosome 14 (14q21-q22) was identified in a large Eastern Pennsylvania Mennonite kindred.

Treatment:  

The phenotype is mild and requires little treatment. Fasting should be avoided and hypoglycemia should be treated.

Prognosis:

Excellent.

Ancillary treatments and support:

Adequate diet, regular pediatric check-ups.

Specialists and specialty centers:

Nutritionist, pediatrician.

References:

Chang, S., Rosenberg, M.J., Morton, D.H., Francomano, C.A., and Biesecker, L.G.:  Identification of a mutation in liver glycogen phosphorylase in glycogen storage disease type VI. Hum. Molec. Genet. 7: 865-870, 1998. PubMed ID: 9536091

Burwinkel, B., Bakker, H.D., Herschkovitz, E., Moses, S.W., Shin, Y.S., and Kilimann, M.W.:  Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI (Hers disease). Am. J. Hum. Genet. 62: 785-791, 1998. PubMed ID: 9529348

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