The Clinical Spectrum of Adrenoleukodystrophy at a Portuguese Tertiary Hospital: Case Series and Review of Literature

TL;DR

This paper presents a case series of four male patients with X-linked adrenoleukodystrophy in Portugal, highlighting the importance of early diagnosis and genetic testing for better outcomes.

Contribution

The study provides new clinical insights into X-linked adrenoleukodystrophy through a Portuguese case series and emphasizes the need for early screening and genetic confirmation.

Findings

Three out of four patients were diagnosed through family screening, with one showing hyperpigmentation.

Two distinct clinical forms were identified: adolescent cerebral adrenoleukodystrophy and isolated adrenal insufficiency.

Genetic analysis revealed two different ABCD1 gene mutations among the patients.

Abstract

Adrenoleukodystrophy, a rare genetic disease associated with the X chromosome (X-ALD - X-linked adrenoleukodystrophy), predominantly affects males and stems from mutations in the ABCD1 gene, responsible for transporting very long chain fatty acids (VLCFA) into peroxisomes. It leads to adrenal insufficiency (AI) and axonal demyelination. In males, the phenotype varies from isolated adrenocortical insufficiency and progressive myelopathy to cerebral adrenoleukodystrophy (CALD). The aim of this case series is to characterize patients with different clinical presentations of X-ALD with follow-up at a tertiary Portuguese hospital.

All four patients were males, and the median age at the diagnosis was 5 years. Three patients were diagnosed through family screening, with the oldest already displaying hyperpigmentation. Two distinct forms were identified: adolescent CALD (25%) and isolated primary adrenal insufficiency (75%). Analytical studies revealed elevated plasma VLCFA levels in all cases, and genetic analysis demonstrated two different mutations in the ABCD1 gene.

This disorder requires early diagnosis for improved prognosis. Screening male children with primary AIfor X-ALD using a VLCFA panel should be considered, particularly after ruling out the most common causes or when learning difficulties are evident. Genetic confirmation of the diagnosis is essential, enabling genetic counseling, family planning, and preimplantation genetic diagnosis.

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