Review Question - QID 107082

The symptoms of developmental regression, a cherry red macula, hepatosplenomegaly, and the foamy histiocyte point towards a diagnosis of Niemann-Pick disease. Sphingomyelinase is deficient in this child.

Niemann-Pick disease is a an autosomal recessive lysosomal storage disease caused by a deficiency in the lysosomal enzyme sphingomyelinase. This deficiency results in the accumulation of sphingomyelin. This can be easily seen in macrophages (histiocytes) as foamy cells (Figure B). The typical presentation of this disease is hepatosplenomegaly, thrombocytopenia, a cherry red macula (Figure A), failure to thrive, and neurodegeneration. Death typically occurs by the age of 3. There is an increased risk of the disease in the Ashkenazi Jewish population.

McGovern and Schuchman provide an in depth review of the clinical presentation of Niemann-Pick disease. The first sign of the disease is hepatosplenomegaly becoming noticeable by the age of 3 months, with continued worsening after this age. Neurological development does not proceed any further than the 1-year-mark when neurological deterioration begins. The classic cherry red spot is seen in nearly every case. Interstitial lung disease results from the sphingomyelin accumulating in pulmonary macrophages leading to recurrent respiratory infections.

The National Center for Biotechnology Information in Genes and Disease discuss that there are three forms of Niemann-Pick disease. The first is Type A which is the acute infantile form as seen in the present case. The second is Type B which is not as common but is chronic and a non-neurological form. The final is Type C which is a distinct form of the disease related to defective cholesterol homeostasis. Patients with Type C have been shown to have a defective ability to release cholesterol from lysosomes resulting in accumulation of cholesterol within the lysosome.

Figure A shows the classic cherry red spot on the macula as seen in Niemann-Pick disease. Figure B shows a bone marrow aspirate showing a foamy histiocyte.

Incorrect Answers:
Answer 1: Iduronate sulfatase is deficient in Hunter's syndrome.
Answer 2: Alpha-L-iduronidase is deficient in Hurler's syndrome.
Answer 3: Arylsulftase A is deficient in metachromatic leukodystrophy.
Answer 5: Hexosaminidase A is deficient in Tay-Sachs disease.