Endocrine Abstracts

Adrenoleukodystrophy (ALD) is a monogenic, X-linked hereditary disorder. Mutation in the ABCD1 gene results in the adrenoleukodystrophy protein (ALDP) deficiency which is involved in the intracellular transport and metabolism of very long-chain fatty acids (VLCFAs). Consequently, VLCFAs accumulate in the central and peripheral nervous systems and adrenal glands leading to the destruction of affected tissues and specific symptoms and signs. There are four distinct types of ALD with adrenomyeloneuropathy being an adult variant. We present a male patient who was hospitalized at the age of 47 with a clinical picture of adrenal insufficiency and progressive paraparesis that made him reliant on a wheelchair. The adrenomyeloneuropathy was suspected. Laboratory results showed low serum cortisol level and normal levels of renin and potassium. The VLCFAs analysis showed the elevated concentration of cerotic acid (C26:0) as well as the elevation of cerotic and lignoceric (C24:0) to behenic (C22:0) fatty acids ratios which confirmed the clinical diagnosis. Genetic testing revealed the hemizygous variant of uncertain meaning in the ABCD1 gene [c.251C>T (p.Pro84Leu)]. Replacement therapy with hydrocortisone was started and since renin, potassium, and blood pressure values were normal, there was no need for mineralocorticoid substitution. At the very beginning of the treatment, the patient took smaller doses of glucocorticoids, which did not lead to the neurological improvement. Because of the above, the total daily hydrocortisone dose was gradually increased to 40 mg and he was able to walk with the help of a cane. As our patient had two daughters, genetic counselling and testing were arranged. Both daughters were healthy but heterozygous carriers of the ABCD1 gene mutation. For heterozygous female carriers, the probability for transmission of the affected gene is 50% for both sons and daughters. It should be taken into account that all affected sons develop disease while daughters are mostly mutation carriers. Therefore, planned pregnancy with the preimplantation genetic testing (PGT) and gender selection is a valuable option. PGT involves in vitro fertilization (IVF), biopsy of the blastocyst, and the transfer of the selected embryo into the uterus. PGT is an option for couples who want to avoid gender-related disorders in offsprings and is mostly allowed for medical reasons in different European countries. In our case, despite genetic counselling, the older daughter had an unplanned pregnancy and gave birth to a clinically healthy son (results of genetic testing are awaited). The younger daughter is going to Belgium for a planned pregnancy.