Niemann-Pick Disease type A (early infantile). Sphingomyelinase deficiency. Acute neuronopathic form.
Incidence
It is an autosomal recessive disease. It often occurs in Jews of Ashkenazic origin (1:30,000). The lysosomal enzyme is defective. The gene is located in the short arm of chromosome 11. A point mutation has been found in 25% of Ashkanazi Jews patients.
Clinical Characteristics
This condition is a neurovisceral accumulation of sphingomyelin. The patient shows early failure to thrive, feeding difficulties, hepatomegaly, which usually preceeds evidence of neurological regression and appearance of cherry red spots in the retina. There are foam cells on bone marrow, spleen, liver, lymph nodes and brain. Also vacuolated lymphocytes in peripheral blood smear, absence of significant dysmorphic features and skeletal deformities. Serum acid phosphatase is normal. The liver is larger than the spleen from early life. There may be vomiting, diarrhea, and fever. Protuberant abdomen There is jaundice, ascitis in advanced cases and enlarged lymph nodes. Visceral signs precede neuro signs. Neurological symptoms start at the age of six months and are always present before one year. Neurological symptoms include apathy, loss of development, absence head control, decreased motor activity. There is axial hypotonia and pyramidal signs. Patients show blindness with coarse pendular nystagmus. There is corneal and lenticular opacification is common. Cherry red spots in retina is present in 25-50 % of the cases. There are late seizures, but it is not an important symptom. Head circumference is normal or decreased. Rarely there are decreased deep tendon reflexes or nerve conduction velocity. Children progress to opistotonic position. CSF is normal. EEG is abnormal but non characteristic. The face appearance is unremarkable, but at times there are protruding eyes, epicanthal folds and hypertelorism. There is abnormal pigmentation of the skin, brownish color on the face and extension areas of the limbs and occasionally on the oral mucosa. There is frequently dysplasia of dental enamel. As the condition progress the patient develops ataxia, progressive growth failure, visceromegaly, liver failure. Death occur by the second or third year of life. There is no treatment available.
Precipitants
no
Provocation Tests
no
Diagnostic Procedures
EB-F, EB-W, DB-W. There are foam cells on bone marrow, spleen, liver, lymph nodes and brain. Also vacuolated lymphocytes in peripheral blood smear.