VARIABILITY OF ENDOCRINOLOGIC DYSFUNCTION IN 55 PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY - CLINICAL, LABORATORY AND GENETIC FINDINGS

X-linked adrenoleucodystrophy (ALD) has been shown to be one of the mo st frequent causes of Addison's disease in men, It is characterized by an impaired peroxisomal beta-oxidation of very long chain fatty acids and is associated with mutations of the ALD gene resulting in a defec tive peroxisomal membrane transport protein. There is a striking varia bility of endocrinological and neurological symptoms in patients with ALD, with no clearly evident correlation between mutations of the ALD gene and the different neurological phenotypes, No data on endocrinolo gical symptoms and the ALD genotype have been published so far. We rep ort endocrinological, clinical, laboratory and molecular genetic data from 55 patients with ALD from 34 families. Endocrinological symptoms of adrenal insufficiency were observed in 33 patients, 20 of whom show ed additional neurological symptoms of cerebral ALD or adrenomyeloneur opathy. Isolated neurological symptoms were seen in 12 patients; in ni ne patients there were neither endocrinological nor neurological sympt oms. Mutations of the ALD gene (n = 28) were detected in 50 patients ( including nine sets of brothers) from 32 families. No correlation was found between the ALD gene mutation and endocrinological dysfunction. However, we found that all sets of brothers were concordant for the en docrinological phenotype (cortisol synthesis was reduced in two sets a nd normal in seven sets), whereas four sets showed a discordant neurol ogical phenotype. As yet unknown hereditary factors other than mutatio ns within the ALD gene may interfere with the endocrinological phenoty pe more strongly than with the neurological phenotype of ALD.