Genotypic and Phenotypic Characteristics of Pediatric X-Adrenoleukodystrophy in a Chinese Cohort

This study aimed to investigate the clinical, phenotypic, and genotypic characteristics of pediatric patients with X-linked adrenoleukodystrophy (X-ALD).

Clinical and genetic data were retrospectively analyzed from 14 male pediatric patients with X-ALD (mean age: 6 years 11 months [SD: 1 year 9 months]; age range: 5-10 years) from 14 unrelated families at a single center.

All 14 patients were diagnosed with childhood cerebral adrenoleukodystrophy (CCALD). Initial clinical symptoms were atypical, primarily presenting as cognitive decline and neurological dysfunction, accompanied by elevated levels of very long-chain fatty acids (VLCFAs) in the blood. Brain magnetic resonance imaging (MRI) findings consistently showed characteristic white matter demyelination. Genetic analysis identified ABCD1 gene mutations in all pediatric patients, comprising 12 distinct known mutations. Among these, 9 cases involved mutations in exons 6 to 9, and 3 cases in exons 1 to 2. A total of 13 were missense mutations, while 1 was a coding mutation.

The findings indicate that early symptoms of X-ALD are often atypical. Blood VLCFA levels and ABCD1 gene mutation analysis play a crucial role in early diagnosis. Hematopoietic stem cell transplantation (HSCT) is an effective treatment for pediatric cases with early-stage CCALD.