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 Delta R608 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.