X-linked adrenoleukodystrophy diagnosed in three brothers

Area of Science:

• Genetics
• Neurology
• Endocrinology

Background:

• Adrenoleukodystrophy (ALD) is an X-linked recessive peroxisomal disorder caused by ABCD1 gene mutations.
• It leads to the accumulation of very long-chain fatty acids (VLCFA) in plasma and tissues.
• Currently, no causal treatment exists, but hematopoietic stem cell transplantation (HSCT) and gene therapy are options for early-diagnosed childhood cerebral forms.

Observation:

• This case report details three brothers with ALD diagnosed at different disease stages.
• The eldest was diagnosed at age nine with hearing loss; his younger brother was diagnosed at seven while asymptomatic.
• The mother also carried the ABCD1 gene mutation.

Findings:

• The eldest brother's condition is severe and he was ineligible for HSCT.
• The middle brother, who underwent HSCT, is in good general condition.
• The youngest brother, diagnosed neonatally, has adrenal insufficiency but normal development; HSCT is not currently indicated.

Implications:

• Parental awareness and early genetic testing, including prenatal screening, are vital for managing ALD.
• Prompt diagnosis and intervention can significantly alter disease progression and outcomes.
• Adrenal insufficiency requires management with hydrocortisone, as seen in all affected brothers.