Kutbay N.O.Ozbek M.N.Yurekli B.S.Demirbilek H.2024-07-222024-07-2220190172780Xhttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/14758OBJECTIVES: 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.EnglishAdrenoleukodystrophyATP Binding Cassette Transporter, Subfamily D, Member 1BrainChildFatal OutcomeHumansMagnetic Resonance ImagingMaleMutation, MissensePhenotypeSiblingsYoung Adultcorticotropinhydrocortisonevery long chain fatty acidadrenal insufficiencyadrenoleukodystrophyadultArticlebody heightbody weightcase reportchildclinical articlecontrast enhancementdeathdemyelinationdeteriorationhearing impairmenthormone substitutionhospital admissionhumanhyperpigmentationmalemissense mutationmutational analysisnuclear magnetic resonance imagingnuclear magnetic resonance spectroscopyphenotypepreschool childSanger sequencingseizureshort staturevisual impairmentX chromosome linked disorderyoung adultadrenoleukodystrophybraindiagnostic imagingfatalitygeneticsmissense mutationphenotypesiblingArticle