NiemanniPicki

Niemann-Pick disease, sometimes encountered in nonstandard spellings as Niemanni-Picki, is a group of inherited lysosomal storage disorders characterized by the abnormal accumulation of lipids within cells. The best-described forms are Niemann-Pick disease type A and type B, caused by mutations in the SMPD1 gene which encodes acid sphingomyelinase (ASM); this condition is also known as acid sphingomyelinase deficiency (ASMD). A separate form, Niemann-Pick disease type C (NPC), is due to defects in cholesterol trafficking with mutations in NPC1 or NPC2 genes and presents through a different clinical pathway.

ASMD (types A and B) results from reduced ASM activity, leading to sphingomyelin buildup in macrophages and other cells. Type A typically presents in infancy with failure to thrive, hepatosplenomegaly, and rapid neurodegeneration, often causing early death. Type B is generally non-neurological or late-onset, with hepatosplenomegaly and pulmonary involvement and a wider life expectancy. NPC presents with progressive neurological decline, ataxia, vertical supranuclear gaze palsy, dystonia, and cognitive changes, frequently accompanied by hepatosplenomegaly; disease progression is highly variable.

Diagnosis relies on biochemical and genetic testing. ASM activity measurements in blood or fibroblasts support ASMD, while NPC is suspected with filipin staining showing cholesterol accumulation in cultured cells, followed by NPC1 or NPC2 gene testing. Genetic testing confirms the diagnosis in all forms.

Treatment is supportive and multidisciplinary. For ASMD, enzyme replacement therapy with olipudase alfa has been approved for non-CNS disease, improving organomegaly and pulmonary function in some patients. NPC management includes symptomatic therapies and, in some regions, miglustat to slow neurological progression. Research continues into disease-modifying approaches and gene therapies. Prognosis varies by subtype and severity, with early-onset ASMD typically more severe than later-onset NPC or ASMD type B.