A through F. NPA is a subacutely progressive neurodegenerative disorder of infancy. Developmental milestones may be attained normally for the first several months or occasionally for the first year. Failure to thrive, progressive hepatosplenomegaly, and progressive psychomotor deterioration begin in the first year of life and lead to death in early childhood. Prenatal diagnosis can be performed by acid sphingomyelinase assay of amniocyte or chorionic villus samples. Beginning in infancy or childhood, NPB patients develop progressive hepatosplenomegaly and progressive, diffuse, pulmonary infiltration.
Morbidity is related primarily to pulmonary, hepatic and skeletal involvement.
NPB patients often live to adulthood, but obstructive and restrictive lung disease associated with dyspnea, asthma, recurrent pulmonary infections, and cor pulmonale may limit survival. Accumulation of sphingomyelin-laden macrophages in liver may result in portal hypertension complicated by esophageal varices. Skeletal involvement includes osteopenia and may lead to vertebral body and other skeletal fractures. With rare exception, subjects with NPB do not exhibit progressive neurologic disturbance. Like NPA, prenatal testing of NPB is possible by acid sphingomyelinase assay of amniocyte or chorionic villus samples.