NeuroLearn NeuroHelp Metabolic Lysosomal storage disorders, classification

Background Histopathology & Immunohistochemistry

BACKGROUND AND CLINICAL INFORMATION: Head

Genetics: All types are autosomal recessive.

Clinical types:

Type I: Most common. Usually adult onset but may manifest at any age from birth onwards. Massive collection of Gaucher cells in liver, spleen and long bone. No obvious brain pathology.
Type II: Acute infantile Gaucher disease or neuronopathic type, patient usually die within two years. There is also hepatosplenomegaly.
Type III: The norrbottnian type or subacute or juvenile neuropathoic Gaucher’s disease. Patients develop asymptomatic splenomegaly which progress to hypersplenism. Intellectural deterioration follows. There is also myoclonic epilepsy and spasticity.

Biochemistry: Deficient in activity of glucocerebrosidase (gene on chromosome 1q21) leading to accumulation of cerebroside. Deficiency of saposin C (gene for the precursor molecule is on chromosome 10q21), a co-factor, has been described in a few patients with clinically type III disease.

HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY: Head

Type: Neuropathologic changes in Type II and III diseases are similar. Very little or no Gaucher cells are seen in type I diseases.

Gaucher cells:

Morphology: They measures 20-100 mm and contain one or more nuclei. These cells contain “crumpled tissue paper” like fine to coarsely fibrillar material. The storage material is PAS (+). Gaucher cells have strong tartrate stable acid phosphatase activity and also strong a-glyccerophosphate dehydrogenase activity. Gaucher cells are negative for lipid stain.
Electron microscopy: The fibrillar inclusions are membrane-bound elongated bodies containing a tubular arrangement of the glucocerebroside.
Distribution of Gaucher cells: Gaucher cells are found in subcortical white matter and the cerebellum, typically with a perivascular arrangement. Some demyelination around the cell clusters may be present. The number of Gaucher cells increases in a fronto-occipital direction. They are particularly prominent in the thalamus and pons.

Neuronal loss: The cerebellum can be depleted of Purkinje cells and neurons of the dentate nucleus. There is also variable neuronal loss in the cortex affecting mainly layers III and V. There are also neuronophagia in the basal ganglia, dentate nucleus, the thalamus and pons. Tyep II disease may have extensive neuronal loss in nuclei of the cranial nerve and also olivary nuclei.

Storage material: No storage material in neurons can be detected by light microscopy. EM can show typical tubular inclusions, intraneuronal inclusions containing twisted tubules, and sometimes trilaminar inclusion similar to those seen in adrenoleukodystrophy.

NeuroLearn NeuroHelp Metabolic For Comment: KarMing-Fung@ouhsc.edu

Background Histopathology & Immunohistochemistry