ESPE Abstracts

Introduction & Aim: Adrenoleukodystrophy (ALD) stems from ABCD1 gene mutations, affecting very long-chain fatty acid (VLCFA) metabolism, leading to VLCFA accumulation in tissues. The variable clinical spectrum of ALD underscores the need for early detection to optimize management with pre-emptive treatments. Hematopoietic stem cell transplantation (HSCT) offers curative potential, while symptom management aims to slow progression. We present cases of ALD managed at our center with variable clinical outcomes.

Methods: All cases with a diagnosis of X-linked ALD presenting between2002-2024 were retrospectively reviewed. Demographic data, clinical, laboratory, imaging findings and treatment outcomes were evaluated.

Results: Nine cases from six unrelated families were included. The age when the first ALD symptoms emerged was 4.5 (2-7) years. Age at presentation to endocrinology was 8.3 (1.16-14.16) years. The youngest patient had no symptoms but was the youngest of three siblings from one family with ALD. Parental consanguinity was present in only one family. Family history of ALD was reported for 5/9, consisting of 3 and 2 siblings. The first clinical manifestation of ALD was primary adrenal insufficiency (PAI) in six, manifesting as skin hyperpigmentation (n = 3) or vomiting (n = 3); neurological signs were the first symptoms of ALD in two patients (strabismus, headache). One patient was asymptomatic. Three patients developed neurological involvement after PAI and one patient vice versa. Three patients had isolated PAI and one neurological involvement only. Brain MRI showed evidence of leukodystrophy in seven cases. The plasma VLCFA levels were significantly increased in seven cases and not available in the other two. Genetic testing identified mutation of ABCD1 in five. Two patients underwent HSCT and three patients died during follow-up.

Conclusion: The clinical presentation of ALD is highly variable. Since the time between the onset of the patient's symptoms and diagnosis can be long, and because early diagnosis may be life-saving, clinicians should be alert to ALD in a boy with PAI. Confirmation of ALD typically involves assessing serum VLCFA levels and/or conducting genetic testing for variants in ABCD1. This is especially important for identifying heterozygous women who may carry pathogenic ABCD1 mutations and for asymptomatic siblings.