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

Eskandari, Siawosh K. M.D., M.B.A.
Revenich, Elisabeth G.M. M.D.
Pot, Dirk J. M.D.
de Boer, Foekje B.Sc.
Bierings, Marc M.D., Ph.D.
van Spronsen, Francjan J. M.D., Ph.D.
van Hasselt, Peter M. M.D., Ph.D.
Lindemans, Caroline A. M.D., Ph.D.
Lubout, Charlotte M.A. M.D.

From the Department of Metabolic Diseases, Beatrix Children's Hospital (S.K.E., F.B., F.J.S., C.M.A.L.), and the Department of Surgery (S.K.E.), University Medical Center (UMC) Groningen, Groningen, the Division of Pediatrics (E.G.M.R., M.B., P.M.H., C.A.L.) and the Department of Metabolic Diseases (P.M.H.), UMC Utrecht, and the Department of Stem Cell Transplantation, Princess Máxima Center for Pediatric Oncology (E.G.M.R., M.B., C.A.L.), Utrecht, and the Department of Pediatrics, Gelre Hospital, Apeldoorn (D.J.P.) — all in the Netherlands.

Dr. van Hasselt can be contacted at [email protected] or at the Department of Metabolic Diseases, Wilhemina Children's Hospital, UMC Utrecht, Lundlaan 6, 3584 EA, Utrecht, the Netherlands. Dr. Lindemans can be contacted at [email protected] or at the Department of Stem-Cell Transplantation, Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, the Netherlands. Dr. Lubout can be contacted at [email protected] or at the Department of Metabolic Diseases, Beatrix Children's Hospital, UMC Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, the Netherlands.

Drs. Eskandari and Revenich and Drs. van Hasselt, Lindemans, and Lubout contributed equally to this article.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

New England Journal of Medicine 390(7):p 623-629, February 15, 2024. | DOI: 10.1056/NEJMoa2313398

SUMMARY

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.

Treatment of Wolman's Disease in an Infant

An infant with Wolman's disease, diagnosed in utero, received enzyme-replacement therapy, a fat-restricted diet, and rituximab-based B-cell depletion as a bridge to early hematopoietic stem-cell transplantation.