A 2-month-old male child, presented with 1 month history of pallor and poor weight gain. On physical examination, there was pallor, and moderate hepatosplenomegaly (liver 6 cm and spleen 4 cm palpable below the costal margin). Hemogram showed Hb of 50 gm/L, WBC count of 7.8 × 109/L, platelet count of 53 × 109/L. Liver function tests were deranged with total bilirubin of 4.88 mg/dl, AST 298 IU/L and ALT of 158 IU/L. He had prolonged PT (> 180 s) and APTT (> 180 s) and low fibrinogen level of 108 mg/dl. Serum triglycerides were 392 mg/dl and ferritin was markedly elevated at 8460 ng/ml. In view of above findings, a diagnosis of Hemophagocytic Lymphohistiocytosis (HLH) was suspected. Bone marrow examination revealed infiltration with macrophages which showed eccentric nuclei and vacuolated cytoplasm (Fig. 1), highly suggestive of lipid storage disorder. Evidence of phagocytosis of erythroid precursor cells and lymphocytes by histiocytes was also seen (Fig. 2). Enzyme studies for Gaucher and Niemann-Pick disease were normal. The patient succumbed to progressive liver failure within 10 days of admission. Next generation sequencing from patient’s stored DNA revealed a pathogenic homozygous mutation c.193C > T(p.Arg65Ter) in exon 3 of LIPA gene leading to the diagnosis of Wolman disease (WD).
Fig. 1.
Bone marrow aspirate showing infiltration by histiocytes with eccentric nuclei and vacuolated cytoplasm
Fig. 2.
Panel A- Marrow showing hemophagocytosis of mononuclear cells. Panel B, D- Hemophagocytosis of lymphocytes. Panel C- Hemophagocytosis of erythroid precursor. Hemophagocytosis is indicated by black arrows in all images. Panel A and B are marrow aspirate smears and Panel C and D are imprint smears. (Leishman and Giemsa stain 1000×)
WD is a rare autosomal recessive storage disorder resulting from complete deficiency of liposomal acid lipase enzyme. It presents in early infancy with clinical features similar to familial HLH. Similar clinical overlap has been reported previously and it is important that clinicians should be aware of this rare cause of secondary HLH [1, 2]. Moreover, histiocytes with marked clearing and vacuolation may not always signify the more common storage disorders like Gaucher and Niemann-Pick disease. Rarer enzyme deficiencies may also produce similar morphology picture which could raise diagnostic suspicion.
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References
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