Diagnosis, treatment, and follow-up of a case of Wolman disease with hemophagocytic lymphohistiocytosis

Abstract

Wolman Disease (WD) is a severe multi-system metabolic disease due to lysosomal acid lipase (LAL) deficiency. We report on a WD infant who developed an unusual hemophagocytic lymphohistiocytosis (HLH) phenotype related to WD treated with sebelipase alfa. A male baby came to our attention at six months of life for respiratory insufficiency and sepsis, abdominal distension, severe hepatosplenomegaly, diarrhea, and severe growth retardation. HLH was diagnosed and treated with intravenous immunoglobulin, steroids, cyclosporine, broad-spectrum antimicrobial therapy, and finally with the anti-IL-6 drug tocilizumab. WD was suspected for the presence of adrenal calcifications and it was confirmed by LAL enzyme activity and by molecular analysis of LIPA. Plasma oxysterols cholestan-3β,5α,6β-triol (C-triol), and 7-ketocholesterol (7-KC) were markedly increased. Sebelipase alfa was started with progressive amelioration of biochemical and clinical features. The child died from sepsis, 2 months after sebelipase discontinuation requested by parents. Our case shows the importance of an early diagnosis of WD and confirms the difficulty to reach a diagnosis in the HLH phenotype. Sebelipase alpha is an effective treatment for LAL deficiency, also in children affected by WD. Further data are necessary to confirm the utility of measuring plasma c-triol as a biochemical marker of the disease.

Keywords: Adrenal calcifications; Hemophagocytic lymphohistiocytosis; Lysosomal acid lipase; Oxysterols; Sebelipase alpha; Wolman disease.

Fig. 1

Liver histology results: non-complex lipid accumulation associated with cholesterol crystals. (A) Hematoxylin and eosin staining illustrate a mixed pattern of hepatocytes with microvesicular steatosis and foamy Kupffer cells (histiocytes) (20×). (B) Reticulin stain showing the lobular and portal tract fibrosis (10×). (C) Periodic acid–Schiff staining showing pale Kupffer cells with vacuolated cytoplasm (black arrow) and hepatocytes containing lipid vacuoles (blue arrow) (40×). (D) CD68 immunohistochemical staining demonstrating Kupffer cells with lipid deposits and needle-shaped crystals of cholesterol (40×).

Fig. 2

Abdominal X-ray with calcific adrenal glands (arrows).