Niemann-Pick Disease, Type C2

Background and History: 

Albert Niemann, a German pediatrician, and Ludwig Pick, a German pathologist, described this neurodegenerative disorder caused by defects in lipid (fat) metabolism.  As a result, specific lipids accumulate in cells throughout the body eventually resulting in their death. 

Clinical Correlations: 

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.

Type C2 seems to be an intermediate form of NP disease and is more likely to have prominent lung disease as well.  It often has an onset in the neonatal period and many infants have a rapid downhill course.  It is not unusual for death to occur in the first year of life or earlier.  Normal developmental milestones are seldom achieved.  They often have purposeless movements, seizures, difficulty swallowing, difficulty looking up, and may be ‘floppy’ and limp.  The liver and spleen are less involved than in other forms but it is important to note that there is considerable overlap of symptoms. 

Genetics: 

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. 

Seizures and movement problems can be treated.  Swallowing difficulties should be monitored to avoid aspiration into the lungs.  Pneumonia requires prompt antibiotic treatment. 

Diagnosis and Prognosis: 

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. 

Additional Information