Rapid decline of fertility in a case of adrenoleukodystrophy

Adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN) is a group of genetica lly determined peroxisomal disorders associated with progressive central de myelination, primary adrenal cortical insufficiency (Addison's disease) and , frequently, primary hypogonadism. Recently, testicular dysfunction was de scribed in ALD/AMN patients but no information on sperm characteristics was provided. In this paper we studied the reproductive function of a patient with adult cerebral ALD, focusing our attention on sperm characteristics. A t the time of diagnosis the patient was 22 years old, had high plasma C26 a nd C24 very-long-chain fatty acid (VLCFA) concentrations and adrenal insuff iciency, Plasma testosterone concentration was in the normal range. The pat ient was prescribed a low-fat diet and 'Lorenzo's oil', which led to normal ization of plasma VLCFA concentrations within 3 months of therapy. Semen an alysis showed normal sperm count, gross morphological alterations and reduc ed motility. Electron microscopy analysis of sperm cells showed pathologica l changes in the head, the plasma membrane and the nucleus in 60% of the sp ermatozoa examined, However, isolated motile spermatozoa showed normal mole cular dynamics of phospholipid bilayer surface and physiological responsive ness to progesterone, At the 12 months follow-up, the patient became azoosp ermic and testicular histology showed arrested maturation. To our knowledge , this is the first description of sperm alterations in a post-pubertal ALD patient, in which severe impairment of spermatogenesis and rapid progressi on to azoospermia occurred despite normalization of plasma VLCFA concentrat ions.