One year and 9 months old male child brought with complaints of global developmental delay noted from 6 months of age. On examination child had hepatomegaly and massive splenomegaly. Investigation revealed anemia (9.6gm/dl) and thrombocytopenia (44,000/cumm). Peripheral smear showed few lymphocytes with vacuolated cytoplasm. Bone marrow aspiration showed numerous macrophages with abundant vacuolated cytoplasm suggestive of Niemann pick cells. Bone marrow trephine biopsy showed focal interstitial aggregates and singly dispersed large polygonal cells resembling foamy macrophages with abundant finely vacuolated foamy cytoplasm and small, round centrally placed nuclei. Acid sphingomyelinase enzyme activity is borderline (0.91). Exome sequencing showed homozygous SMPD1 gene mutation (Nucleotide pathogenic variation) c.668G>C (Protein pathogenic variation) p. Cys223Ser.

Lysosomal storage diseases are a group of inherited disorders caused by deficiency of lysosomal enzymes or structural components. The manifestations of lysosomal storage diseases are complicated due to different enzyme deficiency. It has been reported that a range of metabolic diseases resulting in abnormal accumulation of metabolic byproducts may exhibit abnormal cytoplasmic vacuolation of lymphocyte. Therefore, identification of vacuolated lymphocytes in a pediatric patient with developmental delay should trigger more specific testings for metabolic disorders(1).

Reference:

1.   Anderson, G. , Smith V., Malone M., and Sebire N. J.. 2005. Blood film examination for vacuolated lymphocytes in the diagnosis of metabolic disorders; retrospective experience of more than 2500 cases from a single center. J. Clin. Pathol. 58:1305–1310.