Endocrine Abstracts

JOINT709

Introduction: Adrenoleukodystrophy (ALD) is a rare X-linked disorder caused by mutations in the ABCD1 gene, leading to an abnormal metabolism of very long-chain fatty acids (VLCFAs). As a result, VLCFAs accumulate in the adrenal cortex, testes, white matter of the brain and spinal cord.

Case presentation: A 27-year-old male, with a history of alopecia areata, presented to the emergency department complaining of abdominal cramps, nausea, and vomiting that started approximately one week prior to presentation, along with increased cravings for salty foods, daytime sleepiness, and dizziness over the past six months. He had also recently sustained a severe ankle sprain resulting in a calcaneus fracture and an avulsion fracture of the lateral malleolus tip, requiring immobilization in a cast. The physical examination revealed hyperpigmentation of the skin on the mammary areolas and scrotum, low blood pressure (100/70 mmHg) and tachycardia (110 bpm). Laboratory evaluation showed hyponatremia and hyperkalemia. Adrenal crisis was suspected and treatment with Hydrocortisone hemisuccinate and isotonic saline solution were initiated, with a favorable outcome. The diagnosis of primary adrenal insufficiency (PAI) was established based on hormonal test results showing low cortisol levels (4.1 µg/dl) and elevated ACTH levels (1906 pg/ml). The patient was discharged on Hydrocortisone (20 mg/day) and Fludrocortisone (0.1 mg/day) therapy. Despite adequate physical therapy for the ankle sprain, the patient experienced progressive walking difficulties, weakness, and pain in the legs, prompting a neurology referral. He was diagnosed with spastic paraparesis, ataxia, and bipyramidal syndrome. Given the combination of neurological symptoms and PAI, adrenoleukodystrophy was suspected. Evaluation of VLCFAs revealed elevated levels of hexacosanoic acid (1.15 mg/l), along with increased C24/C22 (2) and C26/C22 (0.07) ratios. Genetic testing identified a hemizygous missense variant in the ABCD1 gene, c.1833G>C, p.(Gln611His), classified as likely pathogenic, which was inherited from the patient’s mother who is heterozygous for the same mutation.

Conclusions: ALD is a disorder with variable clinical manifestations, usually including signs and symptoms of PAI and progressive neurological dysfunction. To the best of our knowledge the mutation found in our patient has not been described in the literature, although another missense variant in the same codon, p.(Gln611Arg), was reported in individuals with ABCD1-related phenotypes, emphasizing the importance of the affected amino acid. [1]

References: Turk BR, Nemeth CL, Marx JS, Tiffany C, Jones R, Theisen B, et al. Dendrimer-N-acetyl-L-cysteine modulates monophagocytic response in adrenoleukodystrophy. Ann Neurol. 2018 Sep;84(3):452-462.