Glycogenosis Type IV and Andersenís Disease
Background Histopathology & Immunohistochemistry
BACKGROUND AND CLINICAL INFORMATION:
Summary of glycogenosis Classificaiton of glycogenoses by enzyme deficiency
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 Andersenís disease.
Patients with Andersenís 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.
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 Andersenís 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
JF et al., 1981]
Genetics: The gene is on chromosome 3. All clinical types are
Diagnosis: Biopsy of the skin, liver, and muscle. Enzymatic assay of blood cells can also be used for diagnosis.
HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY:
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.
Polysaccharide deposition is seen in the outer cells of sweat ducts as in
Laforaís disease and sometimes in smooth muscle.
Polysaccharide storage in muscle is rarely massive. However, cases with normal
glycogen content in muscle have also been reported.
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.