High-Dose ERT, Rituximab, and Early HSCT in an Infant with Wolman's Disease

N Engl J Med. 2024 Feb 15;390(7):623-629. doi: 10.1056/NEJMoa2313398.

Abstract

Wolman's disease, a severe form of lysosomal acid lipase deficiency, leads to pathologic lipid accumulation in the liver and gut that, without treatment, is fatal in infancy. Although continued enzyme-replacement therapy (ERT) in combination with dietary fat restriction prolongs life, its therapeutic effect may wane over time. Allogeneic hematopoietic stem-cell transplantation (HSCT) offers a more definitive solution but carries a high risk of death. Here we describe an infant with Wolman's disease who received high-dose ERT, together with dietary fat restriction and rituximab-based B-cell depletion, as a bridge to early HSCT. At 32 months, the infant was independent of ERT and disease-free, with 100% donor chimerism in the peripheral blood.

MeSH terms

  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Chimerism
  • Dietary Fats* / adverse effects
  • Enzyme Replacement Therapy* / methods
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Immunologic Factors* / therapeutic use
  • Infant
  • Rituximab* / therapeutic use
  • Transplantation, Homologous
  • Wolman Disease* / diet therapy
  • Wolman Disease* / drug therapy
  • Wolman Disease* / immunology
  • Wolman Disease* / therapy

Substances

  • Dietary Fats
  • Immunologic Factors
  • Rituximab