Background Histopathology & Immunohistochemistry Differential Diagnosis

BACKGROUND AND CLINICAL INFORMATION: Head

Summary: Hartnup disease is biochemically characterized by defective transport of neutral amino acids (including tryptophan) across the intestine and kidney. It is probably autosomal recessive. Patients have infantile or childhood onset and have a pellagra-like skin rash accompanied by neurologic exacerbations. Pathologically, there is atrophy and gliosis. This disease is named after the family in which it was first discovered.

Genetics: probably autosomal recessive.

Biochemistry:

Defective transport of neutral amino acids across renal tubules and intestine, with excetion of greatly increased amounts of these amino acids in the urine and feces; the excretion of large amount of indicans, mainly indoxyl sulfate, particularly after oral L-tryptophan loading; and an abnormally high excretion of nonhydroxylated indole metabolites.
Loss of tryptophan in urine reduces its availability for the synthesis of niacin (nicotinic acid). Administration of nicotinic acid appears benificial in improving neurologic and dermatologic symptoms.

Clinical features: Babies at birth are normal. The onset is in late infancy or early childhood. The clinical manifestations are very similar to pellagra with intermittent red, scaly rash over the face, neck, hands, and legs. There is also growth failure and developmental delay; episodic personality disorder and uncontrolled temper, psychosis, and episodic cerebellar ataxia. Attaks of disease are triggered by exposure to sunlight, emotional stress, and sulfonamide drugs and last for about 2 weeks. 50% of affected children progressively develop mental retardation.

Diagnosis: Test for tryptophan in urine.

HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY: Head

Generalized brain atrophy, most prominent in the occipital lobes and the cerebellum. Neuronal loss in cerebral cortex is not accompanied by gliosis. There is intense gliosis and neuronal loss in the lateral geniculate body.

Cerebellar atrophy with loss of Purkinje cells, and proliferation of Bergmann's cells.

DIFFERENTIAL DIAGNOSIS: Head

Pellagra: Clinically, they are very similar. Similar loss of neurons in the cerebellum but without gliosis is also seen in pallegra.

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

Background Histopathology & Immunohistochemistry Differential Diagnosis