Summary: Glycogenosis type IV is resulted from deficiency of the branching enzyme a-1,4-glucan:a1,4-glucan 6-glycosyl transferase. This form is rare. There are four or five different clinical types and the most common type is also known as Andersen’s disease. Patients with Andersen’s disease develop liver dysfunction with hepatospenomegaly, progressive cirrhosis and chronic hepatic failure, followed by early death from liver failure or gastrointestinal bleeding. In some children, cardiomyoapthy is a more prominent finding than hepatic dysfunction. Polysaccharide depositions are mainly in the liver and reticuloendothelial system. Depositions in the tongue, heart, and central nervous system have also been described. The muscle involvement is relatively mild. The histologic characteristic is PAS(+) deposition that is resistant to diastase digestion.

Clinical types:

· Andersen’s disease: This type is characterized by infantile onset with hepatospenomegaly, progressive cirrhosis and chronic hepatic failure. Early death from liver failure or gastrointestinal bleeding usually occurs before the age of 4 years. In some children, cardiomyoapthy is a more prominent finding than hepatic dysfunction. Polysaccharide deposition is wide spread but is mainly in the liver and reticuloendothelial system.

· Non-progressive hepatic form: This form has relatively good prognosis although the time of onset and enzymatic deficiency is similar to Andersen’s disease. These patients do not develop progressive liver cirrhosis, skeletal muscle, cardiac or neurological involvement [McConkie-Rosell A et al., 1996; Greene HL et al., 1988]

· Muscle and heart form with infantile onset: This type has poor prognosis. The motor neurons are also involved [Tang TT et al., 1994].

· Juvenile form: The onset may start in the second decade but the long term prognosis is not good because of cardiomyopathy. [Nase et al., 1995; Reusche E et al., 1992; Schroder SS et al., 1993]

· Adult polyglucosan body disease: This is most commonly seen in patients of Ashkenaszi Jewish lineage. This form does not involve the muscle. Patients have progressive distal sensorimotor neuropathy resulting in severe distal denervation and urinary incontinence. There are also mild dementia and white matter lesions. Widespread depositions of polyglucosan bodies are seen in both the CNS and in the peripheral nerve. In patients with Ashkenaszi Jewish background, the branching enzyme level in leukocytes and peripheral nerve is low but the level is normal in skeletal muscle. The enzyme level is normal in patients of non-Ashkenazi bakground with this disease.

· Idiopathic polysaccharide storage disease: This form has juvenile or early-adult onset and manifests with proximal limb- or hip-girdle type of muscle weakness. The branching enzyme level is normal. Patients have myopathy with or without cardiomyopathy. The histopathology is similar to classic branching enzyme deficiency. [Pellissier JF et al., 1981]

Genetics: The gene is on chromosome 3. All clinical types are autosomal recessive.

Diagnosis: Biopsy of the skin, liver, and muscle. Enzymatic assay of blood cells can also be used for diagnosis.

HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY: Head

Andersen’s disease:

· Wide spread polysaccharide storage: Polysaccharide is seen in the liver and reticuloendothelial system (mononuclear phagocytic system), kidney distal tubules, heart, skin, astrocytes in brain and spinal cord.

· Skin: Polysaccharide deposition is seen in the outer cells of sweat ducts as in Lafora’s disease and sometimes in smooth muscle.

· Muscle: Polysaccharide storage in muscle is rarely massive. However, cases with normal glycogen content in muscle have also been reported.

· Polysaccharide: The polysaccharide deposition is PAS(+) but is largely resistant to a-amylase but sensitive to pectinase digestion. The deposition is always positive with colloidal iron. Phosphorylase activity can be demonstrated in the deposits.