Albert Niemann, a German pediatrician, and Ludwig Pick, a German pathologist, described this neurodegenerative disorder caused by defects in lipid metabolism. As a result, specific lipids accumulate in cells throughout the body eventually resulting in their death.
A number of different types of this neurodegenerative disorder have been described but there is considerable overlap in symptoms. Type A seems to be the most severe with onset at about 6 months of age with symptoms of irritability, failure to thrive, and poor feeding. Infants up to that age seem to develop normally with social smiling and appropriate visual responses. After this age, however, they lose interest in their surroundings and become ‘floppy’. The outstanding clinical sign at this stage is the enlargement of liver and spleen. These infants never achieve sitting, walking, or crawling milestones and seldom survive beyond 3 years of age. Type B is caused by mutations in the same gene but is considered to be a distinct clinical disease because of later (juvenile and young adult) onset and a more benign disease course. Patients with type B disease usually do not have the neurologic symptoms but do have enlargement of abdominal organs and often have more severe lung disease. They often live to early adulthood.
Types C1 (D) and C2 are caused by mutations in different genes and seem to have an intermediate form of disease, often with seizures as a prominent component. Onset can occur any time from infancy to adulthood. Signs and symptoms of liver disease are prominent and pulmonary disease is often severe. Unsteadiness (ataxia), difficulty in upgaze, purposeless movements, and difficulties in speech and swallowing are characteristic. Sleep disorders are common. Infants are often ‘floppy’ and limp. Older individuals may have signs of mental disease such as depression or schizophrenia. Few individuals live beyond the second or third decade as a result of severe lung disease.
Niemann-Pick disease of all types is caused by an enzyme defect resulting from a gene mutation. The inheritance pattern is one of autosomal recessive disease in which normal carrier parents each contribute one copy of the mutation to their offspring. The risk of another affected child is 25% for each pregnancy.
The diagnosis is usually made by a neurologist or pediatrician and can be confirmed by enzyme studies. The prognosis is guarded because of the progressive neurological deterioration but there is considerable variation in disease progression. A number of therapies have been tried with some success but results are mixed. Replacement of the defective enzyme seems the most promising at this time but additional research is needed.