A case series of adrenoleukodystrophy in children conceived through in vitro fertilization with an egg donor

Abstract

Objective: To report 3 cases of adrenoleukodystrophy (ALD) in children conceived by in vitro fertilization (IVF) and egg donation.

Design: A case report.

Patients: Patients aged 4-5 years old, evaluated by the University of Minnesota Leukodystrophy Center, who were diagnosed with ALD after being conceived by IVF with oocytes provided by the same donor.

Interventions: One patient received a hematopoietic stem cell transplant from a human leukocyte antigen-matched donor, and 1 patient received autologous lentiviral corrected hematopoietic cells. The disease state in 1 patient was unfortunately too advanced for effective treatment to be administered.

Main outcome measures: Progression of disease after diagnosis or treatment was observed by cerebral magnetic resonance imaging and monitoring the development or advancement of any cognitive, adaptive, and motor deficits.

Results: Patients who received a transplant for ALD successfully experienced little to no disease progression at least 6 months to 1 year after treatment.

Conclusions: These 3 cases of transmission of ALD through oocyte donation and IVF highlight the potential need to implement more comprehensive genetic screening of gamete donors to prevent the transfer of rare but severe genetic diseases through IVF. Further, these cases highlight limitations in carrier screening guidelines that limit reportable variants to pathogenic and likely pathogenic variants.

Keywords: ALD; Adrenoleukodystrophy; case report; genetic testing; in vitro fertilization.

Figure 1

Axial FLAIR images from 3 different boys showing different severity of disease at the time of CALD diagnosis. A. Extensive involvement of CALD, extending further into the subcortical white matter of the temporal and parietal lobes and into the frontal white matter in patient 1. B. Abnormal signal throughout the splenium of the corpus callosum extending symmetrically into the periventricular parietal white matter in patient 2. C. Faint abnormal signal in the splenium of the corpus callosum (dashed white arrow) in Patient 3. FLAIR= Fluid attenuated inversion recovery; CALD= cerebral adrenoleukodystrophy.