Original articleAcid sphingomyelinase deficiency: Prevalence and characterization of an intermediate phenotype of Niemann-Pick disease
Section snippets
Study Subjects
Sixty-four patients with NPD-B were admitted to the Mount Sinai General Clinical Research Center for medical and family histories and physical examinations. The diagnosis of each patient was confirmed by the demonstration of reduced ASM activity in isolated leukocytes and/or cultured skin fibroblasts and by the identification of two disease-causing ASM mutations. Detailed clinical neurologic examinations were carried out by a single examiner, including assessment of mental status, motor and
Results
The median age of the 64 patients was 20.9 years, with a range of 2 to 66 years at the time of the latest examination. Table I details the genotypes and ages of the 33 patients with retinal changes and/or neurologic involvement. The most common neurologic abnormalities were mild hypotonia and/or hyporeflexia, which were found in 10 patients. Three patients had one unusual neurologic abnormality: Patient 52 had a slight intention tremor, patient 54 had a terminal finger-nose tremor, and patient
Discussion
Acid sphingomelinase deficiency has traditionally been categorized as neuronopathic (NPD-A) or non-neuronopathic (NPD-B). Several reports have described patients with a subtle, intermediate form who satisfy criteria for NPD-B but who also have neurologic manifestations including cerebellar signs and nystagmus,3 extrapyramidal involvement,6 mental retardation,7 and psychiatric disorders.8 As in other lysosomal storage diseases,9 it is evident that neurologic manifestations in acid
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Supported by a grant (5 MO1 RR00071) for the Mount Sinai General Clinical Research Center from the National Center for Research Resources, National Institutes of Health (NIH), and by NIH grant K24RR021991-02 (M.M.). M.W. is the recipient of a Mentored Patient-Oriented Research Career Development Award (K23 RR16052-01) from the NIH.