Adrenoleukodystrophy is an X-linked, inherited metabolic disorder. Here, we present 3 clinical cases of different phenotypes with one mutation in ABCD1 gene in one family.
Patient 1: At the age of 9 years, manifestation of neurological symptoms was observed, skin color changed, these symptoms progressed monthly. MRI of the brain showed 13 points on Loes scale.
During the examination, the diagnosis of X-linked adrenoleukodystrophy was suspected; it was confirmed by biochemical (elevation of very long chain fatty acids - VLCFA) and molecular genetic studies (a mutation in exon 1 of the gene ABCD1 (c.871G>A (p.Glu291Lys) in the hemizygous state). The child was diagnosed with X- linked adrenoleukodystrophy, childhood cerebral form, primary adrenal insufficiency, and hormone replacement therapy was prescribed. Six months after the manifestation of the disease the child died.
Patient 2: at the age of 1 year 4 months the boy stopped sitting down, was constantly sleeping, was sluggish. Considering the diagnosed disease in the middle brother, a molecular genetic study was performed, and an identical mutation in the ABCD1 gene was detected. During the examination, primary adrenal insufficiency was diagnosed, hormone replacement therapy was prescribed. Up to 4 years of age during dynamic observation there were no changes in the nervous system, according to MRI of the brain, there were no pathologies. Currently, the boy has X-linked adrenoleukodystrophy: Addison`s disease only.
Patient 3, 14 years: At the time of the examination, there were no complaints. There have never been clinical signs of adrenal insufficiency and neurological symptoms.
The diagnosis of X-linked adrenoleukodystrophy was confirmed by elevation of VLCFA and the presence of a mutation in the ABCD1 gene, as in younger brothers. During ACTH stimulation test (with cosyntropin), cortisol was increased up to 1173 nmol/l.
Sex hormones correspond to puberty stage (Tanner 3).
Given the prolonged absence of primary adrenal insufficiency and the absence of neurological manifestations, the boy may have an asymptomatic X-ALD phenotype.
Conclusion: There is no correlation between the genotype and the phenotype. In this family, the presence of 3 forms of the disease is noted: childhood cerebral form, Addison`s disease only and asymptomatic phenotype. However, progression of the disease is possible; patients require medical follow-up. Factors affecting the development of one form or another are currently unknown.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology