Endocrine Abstracts

Introduction: X-linked adrenoleukodystrophy (X-ALD) is due to mutation in ABCD1 with variable clinical phenotype and severity. Elevated plasma VLCFA is seen in all affected males. However, the clinical phenotype is not collated with VLCFA plasma concentration or by the type of ABCD1 variant. Clinical presentation can be widely variable ranging from childhood cerebral adrenoleukodystrophy (CALD), adolescent CALD, adrenomyloneuropathy and/or adrenal insufficiency. We present a series of patients with X-ALD due to ABCD1 mutation with varying clinical presentation.

Case history: Index patient from the first family presented at the age of 8.5 years with behavioural problems, and rapid neurological deterioration, and MRI brain was typical of X-LAD with Loes score of 15. The genetic testing confirmed maternally inherited ABCD1 splicing variant. His ACTH was elevated with suboptimal cortisol to synacthen test, and he was started on hydrocortisone treatment. His electrolytes were normal with normal renin and aldosterone. Unfortunately, due to his advanced MRI changes, he could not be offered haematopoietic stem cell transplant (HSCT). His 4-year-old and 11-year-old brothers were investigated and found to have elevated VLCFA with primary adrenal insufficiency and started on hydrocortisone therapy and the electrolytes, renin and aldosterone and MRI brain were normal. The fourth patient from another family was identified with ABCD1 mutation at the age of 10 months due to a strong family history of X-ALD. He was noted to have glucocorticoid deficiency with preserved neurological function. Several of his uncles had been diagnosed with X-ALD and needed only hydrocortisone and some developed neurological dysfunction later in the adulthood. One of his family members was also identified with gonadal failure at the age of 18 years needing testosterone treatment.

Discussion: Due to the deposition of VLCFA predominantly in the zona fasciculata of adrenal cortex, glucocorticoid deficiency is a consistent feature in these patients with spared mineralocorticoid at presentation. However, regular monitoring of electrolytes and plasma renin activity will be essential to identify evolving mineralocorticoid deficiency. Due to the deposition of VLCFA in the gonads, primary testicular failure could be a feature of X-ALD.