Introduction: X-linked adrenoleukodystrophy (X-ALD) is a rare autosomal recessive neurodegenerative disease caused by a mutation in the ABCD1 gene. Although its clinical presentation varies, X-ALD is generally characterized by progressive demyelination of the central nervous system, primer adrenal insufficiency, and elevated plasma very long-chain fatty acid (VLCFA) levels. Herein, we aimed to present a case of X-ALD with normal VLCFA caused by a pathogenic variant in ABCD1 gene.
Case: Twelve years seven months old boy was referred to our department because of hyperpigmentation, weakness, downward trend in his school performance since last year. He was born with birth weight of 1,750 grams at 32 gestational weeks after uneventful pregnancy. His neuromotor milestones were normal. The parents were no relatives. Two of his cousins were followed by another center due to adrenal insufficiency. In his physical examination, height was 165.6 cm (1.32 SDS), weight was 46.2 kg (-0.16 SDS), body mass index was 16.9 kg/m2 (-0.99 SDS), blood pressure was 110/70 mmHg (50th centile), and his puberty was compatible with Tanner Stage 4. Muscle strength was 5/5 and hyperpigmentation was observed in his oral mucosa and nipples. In the laboratory examination, sodium 139 mEq/L, potassium 4,4 mEq/L, chloride 106 mEq/L, glucose 96 mg/dl, ACTH >1250 pg/ml, cortisol 3,8 µg/dl, aldosterone 66 pg/ml (N: 82-192), plasma renin activity 2,01 ng/ml/s (N:0,5-3,3). Complete blood count, thyroid functions, lipid profile and gonadotropin levels were normal. The diagnosis of primary adrenal insufficiency was established and hydrocortisone was started (15 mg / m² / day). VLCFA examinations were found to be normal [C22: 32 mg / L (N: 10.5-51), C24: 28 mg / L (N: 8.5-37.5), C26: 0.3 mg / L (N: 0.1 -0,6), C24 / C22: 0,83 (N: 0-1,16), C26 / C22: 0,01 (N: 0,02)]. Cranial T2A-FLAIR A MRI revealed bilateral hyperintense areas in parieto-occipital white matter. Genetic analysis of ABCD1 revealed a hemizygote pathogenic variant in exon 6 that was previously reported [NM_000033:c.1571G>A(p.Trp524*) ]. Family screening is planned. Recently, the patient is followed by pediatric metabolism and pediatric neurology clinics.
Conclusion: In patients with primary adrenal insufficiency, X-related adrenoleukodystrophy should be considered in differential diagnosis even if plasma VLCFA levels are normal. ABCD1 gene analysis should be considered in the presence of clinical suspicion and radiological findings
Keywords: Primary adrenal insufficiency, adrenoleukodystrophy, ABCD1
19 - 21 Sep 2019
European Society for Paediatric Endocrinology