Late identification of X-linked Adrenoleukodystrophy: Case report — ASN Events

Late identification of X-linked Adrenoleukodystrophy: Case report (#342)

Timothy Middleton 1 , Avinash Suryawanshi 1 , Kirtan Ganda 1
  1. Concord Repatriation General Hospital, Concord, NSW, Australia

Context: Adrenoleukodystrophy (ALD) is a rare, X-linked genetic condition caused by mutations in the ABCD1 gene that results in accumulation of very long chain fatty acids (VLCFA) in various tissues1. This results in central nervous system demyelination and impaired steroidogenesis in the adrenal cortex and testis. We report the late diagnosis of X-linked ALD in a 57-year-old man many years after onset of primary adrenal insufficiency and paraparesis.

Case History: A 57-year-old gentleman was referred to the endocrinology clinic for assessment of bilateral gynaecomastia of six months duration. His past medical history was remarkable for spastic paraparesis, diagnosed four years prior and skin hyperpigmentation, since the age of 5 years.

Physical examination findings included generalised hyperpigmentation (including palmar creases and gums), BP of 90/60mmHg, non-tender gynaecomastia and bilateral testicular atrophy. Lower limb findings were consistent with paraparesis combined with sensory loss. Gait was paraparetic and wide-based.

Results: In light of hypotension and hyperpigmentation, the possibility of primary adrenal insufficiency was considered and confirmed with an early morning cortisol of 72nmol/L and a markedly elevated ACTH level of 1,118pmol/L. Investigations for the gynaecomastia revealed prolactin, oestradiol, testosterone within the reference range, however LH was 1.6 times the upper limit of normal. The combination of primary adrenal insufficiency (likely childhood onset), partial testicular failure (leading to gynaecomastia) and spastic paraparesis suggested X-linked ALD as a possible unifying diagnosis. A serum VLCFA panel revealed elevated concentrations of C26 and C24 consistent with X-linked ALD. Subsequent genetic testing confirmed a mutation in the ABCD1 gene. Treatment with hydrocortisone resulted in increased energy levels.

Conclusions: We have reported a 57-year-old man with a late diagnosis of X-linked ALD manifested by childhood onset primary adrenal insufficiency, primary hypogonadism and paraparesis. Thus, ALD should be considered in a patient with primary adrenal insufficiency and neurological abnormalities.