| Type | OMIM | Gene (chromosome); all are autosomal recessive | Clinical features |
| Niemann-Pick disease type A | 257200 | SMPD1 (11p15.4-p15.1) | Onset in first months of life; hepatosplenomegaly, interstitial lung disease, feeding difficulty, loss of early motor skills, rapidly progressive loss of neurologic function, peripheral neuropathy, macular cherry red spot. |
| Death, typically from respiratory failure, occurs by age two or three years. | |||
| Diagnosis confirmed when residual acid sphingomyelinase activity is <10 percent of control. | |||
| Niemann-Pick disease type B | 607616 | SMPD1 (11p15.4-p15.1) | Onset in infancy or childhood; hepatosplenomegaly, thrombocytopenia, short stature with delayed skeletal maturation, interstitial lung disease, hyperlipidemia, ocular abnormalities. Neurologic abnormalities (cerebellar signs, nystagmus, extrapyramidal involvement, mental retardation, psychiatric disorders, and peripheral neuropathy) occur in about 30 percent. |
| Generally less severe than NPD-A, with most affected patients surviving into adulthood. | |||
| Diagnosis confirmed when residual acid sphingomyelinase activity is <10 percent of control. | |||
| Niemann-Pick disease type C | 257220 607625 | NPC1 (18q11-q12) NPC2 (14q24.3) | Wide phenotypic spectrum. Onset ranges from in utero to infancy, childhood, or adulthood. |
| • Antenatal cases present with fetal ascites. | |||
| • Neonatal onset occurs with severe hepatic disease and/or respiratory failure; other neonates have hypotonia and developmental delay with little or no hepatic and pulmonary involvement. | |||
| • Most cases have onset in middle to late childhood after normal early development. Neurologic manifestations are cerebellar involvement (clumsiness, gait problems, eventual frank ataxia), vertical supranuclear ophthalmoplegia, and slowly progressive cognitive deterioration. Dystonia, dysarthria, dysphagia and seizures are common. Death typically occurs from aspiration pneumonia in the second or third decade of life. | |||
| • Adult onset is usually similar to juvenile/childhood cases but with slower progression. Adult cases may also present with cognitive dysfunction or psychiatric disturbances. | |||
| Diagnosis confirmed by impaired LDL cholesterol esterification and positive filipin staining in cultured skin fibroblasts. |
