Acid sphingomyelinase deficiency: Prevalence and characterization of an intermediate phenotype of Niemann-Pick disease

Objective: To document the prevalence of neurologic disease in Niemann-Pick disease (NPD) NPD-B. Study design: Sixty-four patients with NPD-B had detailed neurologic and ophthalmologic evaluations. The presence of neurologic abnormalities was compared with genotype. Results: Nineteen of 64 patients (30%) had neurologic abnormalities, which were minor and nonprogressive in 14 (22%), and global and progressive in 5 (8%). In these five patients, the onset of neurologic difficulties occurred between 2 and 7 years of age and was associated with peripheral neuropathy, retinal abnormalities, and the Q292K mutation. No patients with at least one copy of ΔR608 had neurologic involvement. Conclusions: The majority of patients with NPD-B have no neurologic abnormalities. In patients with neurologic abnormalities, the findings can be minor and static or severe and progressive. The latter phenotype follows a course distinct from that of classic NPD-A and is associated with the Q292K mutation and characteristic retinal findings. Thus, similar to other lysosomal storage disorders, there is a broad spectrum of neurologic abnormalities in acid sphingomyelinase deficiency, which makes the current classification scheme inaccurate.