X-linked adrenoleukodystrophy: a case report

Abstract

In this article, we described а clinical case of a 32-year-old patient with late diagnosis of adrenomyeloneuropathy manifested with gradually increasing neurologic symptoms, mistakenly considered as hereditary spastic paraparesis, later joined by adrenal insufficiency. It is known that ALD is characterized by a pronounced phenotypic polymorphism, which is associated with differences in penetrance and expression of the abnormal gene. The patient was examined for pathogenic mutations associated with spastic paraplegia and hereditary diseases with similar phenotypic manifestations (Neurodegenerative Diseases panel including analysis of 723 genes). No significant changes meeting the search criteria were found. However, the absence of point mutations associated with ALD does not exclude this diagnosis, but requires the exclusion of chromosomal rearrangements by sequencing the ABCD1 gene. This study was not performed on the patient, which subsequently led to the misdiagnosis. Despite the fact that current clinical guidelines allow the diagnosis of ALD without genetic confirmation, due to the variety of ALD “masks” and frequent untimely diagnosis of this disease, sequencing of the ABCD1 gene is advisable. In order to correct adrenal insufficiency, the patient was prescribed hormone replacement therapy (HRT) with hydrocortisone, which eliminated the main clinical manifestations and partially laboratory signs of hypocorticism. However, corticotropin levels indicated inadequacy of HRT and increased risk of secondary corticotropinoma growth. However, the patient has been receiving intrathecal therapy with the GABA agonist baclofen for the past five years. The literature has not yet described the response of stress hormones to intrathecal administration of baclofen in patients with primary hypocorticism. The few data available indicate that GABA agonists may have a multidirectional effect on hypothalamic-pituitary function; therefore, it is difficult to determine the contribution of this effect on corticotropin secretion in this patient.