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Neuro Endocrinol Lett. 2019 Mar 11;40(1):36-40. [Epub ahead of print]

A Distinct Clinical Phenotype in Two Siblings with X-linked Adrenoleukodystrophy.

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Celal Bayar University Faculty of Medicine, Division of Endocrinology and Metabolism, Manisa, Turkey.
University of Health Sciences, Gazi Yasargil Education and Training Hospital, Department of Pediatrics Endocrinology, Diyarbakir, Turkey.
Ege University Faculty of Medicine, Division of Endocrinology and Metabolism, Izmir, Turkey.
Hacettepe University Faculty of Medicine, Department of Pediatrics Endocrinology, Ankara, Turkey.



X-linked adrenoleukodystrophy(X-ALD) is a rare X-linked recessive metabolic disorder. The mutations in the ATP Binding Cassette Subfamily D Member 1 (ABCD1) gene account for the underlying molecular mechanism. Herein, we present two siblings with X-ALD due to a missense, presumably identical, ABCD1 mutation, who had extremely distinct clinical phenotypes.


Patient 1 (6y/o) was admitted with primary adrenal insufficiency (PAI). His VLCFA analysis and cranial MRI suggested the diagnosis of X-ALD with no cranial involvement. Although the PAI was successfully managed using hydrocortisone replacement therapy, during follow-up he was admitted with the complaints of perception impairment, seizures, loss of vision and deafness suggesting cranial involvement which was not able to be recovered despite intensive supportive therapies; in the end patient died. Patient 2 (21y/o) had mild symptoms of PAI with no organ manifestation. He was undertaken to a molecular genetics analysis for ABCD1 gene due to history of his brother. His VLCFA analysis revealed mildly elevated C26, C22 and C26/C22 ratio suggesting ALD diagnosis. However, his cranial imaging and other results were within normal limits.


Two siblings with X-ALD due to presumably an identical, missense ABCD1 mutation and distinct clinical phenotype have confirmed the lack of phenotype-genotype correlation and proved the essential role of molecular genetics analysis in the early diagnosis. It is crucial to follow up for the development of cranial involvement and decide a bone marrow transplantation which is the only option that can prevent the progression of the disease, thus extend the lifespan.


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