A distinct clinical phenotype in two siblings with X-linked adrenoleukodystrophy
No Thumbnail Available
Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
OBJECTIVES: 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. MATERIAL AND METHODS: 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. CONCLUSION: 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. ©2019 Neuroendocrinology Letters.
Description
Keywords
Adrenoleukodystrophy , ATP Binding Cassette Transporter, Subfamily D, Member 1 , Brain , Child , Fatal Outcome , Humans , Magnetic Resonance Imaging , Male , Mutation, Missense , Phenotype , Siblings , Young Adult , corticotropin , hydrocortisone , very long chain fatty acid , adrenal insufficiency , adrenoleukodystrophy , adult , Article , body height , body weight , case report , child , clinical article , contrast enhancement , death , demyelination , deterioration , hearing impairment , hormone substitution , hospital admission , human , hyperpigmentation , male , missense mutation , mutational analysis , nuclear magnetic resonance imaging , nuclear magnetic resonance spectroscopy , phenotype , preschool child , Sanger sequencing , seizure , short stature , visual impairment , X chromosome linked disorder , young adult , adrenoleukodystrophy , brain , diagnostic imaging , fatality , genetics , missense mutation , phenotype , sibling