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Neiman pick disease Type C – Classical morphology

A 3-month-old male child presented to the OPD with complaints of cough and respiratory distress of one month duration. There was history of sweating while feeding. There is history of death of a sibling at 3 months of age. On examination intercostal, substernal retractions and hepatosplenomegaly were present. His CBC revealed lymphocytic leucocytosis. CRP was elevated. Blood culture, CBNAAT were negative. Chest Xray and CT Chest revealed bilateral lung consolidation. Child was put on Oxygen support and empirical antibiotics later shifted to antifungals suspecting fungal cause of pneumonia. Since there was no response to antibacterial and antifungals primary immunodeficiency work up was initiated and it revealed borderline B and T cell deficiency. Immunoglobulin titre was done which was absolutely normal. CMV RTPCR was done suspecting TORCH group of infection which turned out to be positive and child was started on Tab. Valgancyclovir. Childs oxygen requirement reduced gradually

However, in view of persistent pneumonia and hepatosplenomegaly enzymatic workup for storage disorders and bone marrow studies was done. Bone marrow aspirate revealed few histiocytes with abundant foamy soap bubble cytoplasm scattered singly. Morphological findings were suggestive of storage disorder and further molecular studies were advised. Enzymatic studies showed normal levels of glucocerebrosidase enzyme and borderline values for sphingomyelinase hinting at Nieman pick disease. Next Generation Sequencing (NGS) study for storage disorders was ordered which revealed homozygous mutation for NPC2 gene on EXON 2 suggesting Nieman Pick disease type C2(NP C2). Child was discharged with oxygen concentrator

Nieman pick disease is a lysosomal storage disorder with autosomal recessive inheritance. Based on clinical manifestation it is classified into three types – Type A, Type B and Type C. Type C is more common than Type A & B combined and is caused by mutation in NPC1 and NPC2 genes, majority being due to NPC1. NPC mutation causes primary defect in lipid transport resulting in cholesterol and ganglioside accumulation in the affected cells. Classical morphology shows foamy macrophages with soap bubble cytoplasm. CMV infection and borderline enzymatic levels created diagnostic confusion however subtle morphological clue was confirmed by demonstration of mutation on NGS.