Addison disease as presenting manifestation of one patient with adrenoleukodystrophy and identification of a novel ABCD1 gene mutation

Abstract

Objective To identify the clinical manifestations, imaging findings, and genetic mutation characteristics in a rare case of adrenoleukodystrophy(ALD)with adrenocortical dysfunction(Addison′s disease)as the first manifestation. Methods The clinical data of the proband and his family members were comprehensively collected, and ABCDl gene sequencing was meticulously performed for the proband and his mother using high-throughput sequencing method. Results The patient presented with systematical skin pigmentation accompanied by fatigue in early stage, arose stroke-like episodes manifested as a sudden loss of consciousness and incontinence induced by high fever, and followed by progressive unclear speech, unstable walking and worsening vision. Serum very long-chain fatty acid(VLCFA)concentration increased over normal range. The brain MRI showed an abnormal signal of the symmetric distribution of the bilateral corpus callosum. A new c. 874_876del GAG hemizygous variation in the patient′s ABCD1 gene was detected, while his mother had a nucleotide heterozygous variation to this site . Conclusion The diagnosis of ALD requires a combination of clinical manifestations, imaging examination, and serum VLCFA level measurement, while the detection of ABCD1 gene mutations is considered to be the most reliable approach. Key words: Adrenaleukodystrophy; Adrenal insufficiency; Addison disease; ABCD1 gene