Abstract

Introduction: Niemann–Pick Disease (NPD) is an autosomal recessive disorder, characterized mainly by the accumulation of lipids, mostly sphingomyelin and cholesterol, in different organs such as liver, spleen, bone marrow, lungs and brain. The Sphingomyelins accumulate in lysosomes, which are responsible for carrying substances in and out of the cell. NPD is classified in 4 types: Types A, B, C and D. In type A and B, there is deficiency of acid sphingomyelinase which helps to break down Sphingomyelins, whereas Type C and D are caused by a defect in the transport of intracellular cholesterol. Thus, the 4 disease types can be grouped into 2 main categories: Type (I) which includes type A and B; and Type (II) which includes type C and D. Each type affects different organs. Symptoms depend upon severity of the disease and organs involved. The diagnosis is done by measurement of enzyme activity in peripheral white blood cells or in cultured fibroblasts. The pathologic hallmark in Niemann-Pick disease (NPD) types A and B is the characteristic lipid-laden foam cell termed as Niemann-Pick cells on bone marrow examination. Mutation analysis for detection of SMPD1 mutations is a complex procedure but can be done if facilities are available. There is no specific treatment for Niemann-Pick Disease. Type A is a severe form of disease, with average life span of 18 months. In all other types, treatment is aimed at controlling levels of cholesterol. Newer drugs like Miglustat which is able to delay neurodegeneration, β-cyclodextrin- hydroxypropyl (HBP-CD) which is claimed to attenuate clinical symptoms are being investigated in trials. Genetic counseling and genetic testing are recommended for families who have history of Niemann–Pick disease.

Case Report: A 7 year old female child was brought with complains of abdominal distension which started at the age of 3 years. There was also history of intermittent fever, difficulty in walking in the form of repeated falls and multiple episodes of tonic clonic seizures since last 1 year. development history was significant since the the patient had normal development till the age of 3 years following which she started lagging behind in all aspects of development. She also had a younger sibling having similar complaints of abdominal distension and developmental delay. On examination patient had global developmental delay with mild mental retardation (IQ= 68). There was significant abdominal distension with moderate hepatosplenomegaly. Bone marrow examination was done which showed characteristic lipid-laden foam cell termed ie Niemann-Pick cells. Lysosomal enzyme studies confirmed the diagnosis of pieman pick disease type B. Anticonvulsants (Levipril) was started. Patient was discharged with an advice for regular follow up. Parents were referred for genetic counseling.

Conclusion: Sphingomyelinase deficiency or Niemann-pick disease should be suspected in pediatric patients presenting with hepatosplenomegaly and developmental delay. The diagnosis is usually done by bone marrow examination and lysosomal enzyme studies. Genetic counseling should be offered to parents having children with Niemann-pick disease.

Keywords: Niemann-pick disease, sphingomyelinase, Developmental delay, Genetic counseling.counseling.