Endocrine Abstracts

Introduction and Objective: X-linked adrenoleukodystrophy (X-ALD) is a rare disease caused by a mutation in the ABCD1 gene (Xq28). It is characterized by the absence of very long-chain fatty acids (VLCFAs) degradation, leading to their accumulation primarily in the central and peripheral nervous system, adrenal cortex, and gonads. It presents a variable clinical spectrum and prognosis. The aim of our study is to describe the characteristics of all X-ALD patients under follow-up at the Adult Inborn Errors of Metabolism Unit at Virgen del Rocio University Hospital (Seville).

Methods: Retrospective observational study. The following variables were collected: gender, current age and age at diagnosis, symptoms, age of symptom onset, and treatment (dietary, pharmacological, hematopoietic cell transplantation [HCT], and gene therapy). Quantitative variables are expressed as median [p25-p75], and qualitative variables as n(%).

Results: 21 patients. 10 (47.6%) were males. Patients had a median age of 39.2 [23.9-53.8] years and were diagnosed at a median age of 7.1 [21.3-50.13] years. The most frequent mutation was c.971G>A (p.Arg324His). Regarding males, 7 (70%) were diagnosed as index cases, and 8 (80%) were symptomatic, with a median onset of symptoms at 14.5 [4-50.5] years: 60% adrenal insufficiency, 30% cerebral involvement, 30% myeloneuropathy, and 10% gonadal insufficiency. Concerning females, 10 out of 11 (90.9%) were diagnosed due to having an affected family member, and 4 (36.3%) had symptoms, with a median onset at 45 [41.5-56] years: 27.2% myeloneuropathy, 9.1% premature ovarian failure, and 0% adrenal insufficiency. 81% had elevated VLCFAs at diagnosis (90% of males and 72.7% of females): C22 52 [28-65] µmol/l, C24 59 [41-67] µmol/l, C26 1.51 [0.86-2.12] µmol/l, C24/C22 1.24 [0.95-1.45], and C26/C22 0.029 [0.016-0.063]. Regarding treatment, 8 (38.1%) follow a saturated fat-restricted diet, 4 (19%) take Lorenzo’s oil, 6 (28.4%) hydrocortisone, 5 (23.8%) fludrocortisone, and 1 (4.8%) testosterone. One male underwent HCT, and another received gene therapy, with clinical stability of cerebral lesions in both patients. There was 1 death of a male during follow-up.

Conclusions: In our cohort, adrenal insufficiency is the most frequent symptom in males, and a high percentage of females exhibit some symptoms. Communicating data from X-ALD patient series is essential to understand the clinical spectrum of the disease and the true prevalence of symptomatic females.