ESPE Abstracts

Introduction: X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder, caused by mutations in the ABCD1 gene localized on Xq28, affecting the adrenal cortex, nervous system, and testicular functions. It is characterized by the deficiency in transporting very long-chain fatty acids (VLCFA). We present a case of a boy diagnosed with adrenoleukodystrophy and discuss the importance of family screening, as his sibling was diagnosed through this method.

Case Presentation: A 14-year-old boy presented to the general pediatrics clinic with complaints of fatigue and was referred to our clinic due to elevated TSH levels. He was born at term birth weighing 4000g. Over the past five years, skin darkening was noted. He did not have alacrima or dysphagia, his school performance was good. There was no consanguinity between the parents. On admission, his height was 173.5 cm (98th percentile), weight was 50 kg (78th percentile), BMI was 16.6 kg/m². His blood pressure was 113/81mmHg, he has hyperpigmentation. He was in Tanner stage 5 of puberty. Laboratory tests showed normal hemogram and biochemistry, subclinical hypothyroidism, low cortisol, high ACTH levels. Abdominal ultrasound revealed normal adrenal glands. Hydrocortisone was started at 15 mg/m²/day. Tests for 21-hydroxylase antibody, thyroid, diabetes, celiac disease autoantibodies were negative. Lipids and initial VLCFA levels were normal. Genetic analysis identified a homozygous c.631C>T p.(Leu211Phe) variant in the ABCD1 gene. VLCFA levels were re-evaluated and consistent with ALD (Table 1): Cranial MRI was normal, LOES score was 0. The patient was consulted with the pediatric metabolism and neurology clinics. Due to the mild-moderate form of ALD, a bone marrow transplant (BMT) was not considered, close monitoring was planned. The patient's asymptomatic 5-year-old brother was screened, revealing low cortisol, high ACTH, VLCFA levels consistent with ALD. Hydrocortisone was initiated at 10 mg/m²/day. Both siblings were started on Lorenzo's oil and VLCFA-poor diet.

Conclusion: X-ALD can present with a wide range of symptoms, from primary adrenal insufficiency to severe neurocognitive degeneration. Early BMT in the initial stages of cerebral ALD can halt disease progression and even result in improvements. Early diagnosis and family screening, as in our cases, are crucial.