Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease

Journal article

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

Authors: Potter, JE; Petts, G; Ghosh, A; White, FJ; Kinsella, JL

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: BioMed Central
• Journal: Orphanet Journal of Rare Diseases
• Volume: 16
• Issue: 1
• Pages: 235-235
• Article number: 235
• Publication date: 2021-05-21
• DOI: 10.1186/s13023-021-01849-7
• EISSN: 1750-1172
• ISSN: 1750-1172
• Language: English
• Keywords: Stem cell; Sepsis; Medicine; Disease; Vomiting; Hematopoietic stem cell transplantation; Biology; Immunology; Enzyme replacement therapy; Internal medicine; Substrate reduction therapy; Gastroenterology; Hepatosplenomegaly