Clinical And Genetic Analysis Of 6 Cases Of X-Linked Adrenoleukodystrophy

Objective: The clinical and molecular genetic characteristics of 6 cases of X-linked adrenoleukodystrophy(X-ALD)patients were reported to raise awareness and reduce misdiagnosis and mistreatment.Methods: The clinical manifestations,laboratory and imaging exami nations,gene testing results and treatment and genetic counseling of 6 patients with X-ALD who were admitted to the second hospital of hebei medical university from 2015 to 2020 were retrospectively analyzed.Result:Clinical feature:All 6 patients were male.Cases 1-4 are of childho od cerebral ALD(CCALD),which are mainly manifested as limb dysfun ction(4 cases),convulsions(3 cases),visual acuity(1 case),and intelle ctual decline(1 case).Case 5 showed adolescent cerebral ALD(Adol C ALD),presenting with blackened skin,weakness,poor appetite,and wal king instability.Case 6 for adrenomyeloneuropathy(AMN),characterized by progressive double lower limbs spastic paraplegia.Laboratory examination:In all 6 patients,plasma Very long chain fatty acids(VLCFAs)andadrenocorticotropic hormone(ACTH)increased,serum cortisol(COR)and 24-hour urinary free cortisol(24h UFC)decrea sed.Imageological examination:Cranial MRI plain scan in cases 1,3~6 all showed multiple white matter region T1 low signals?T2 and FLAIR slightly hyperintensity signals.In case 6,Cranial MRS examination show ed that the peak of choline complex(Cho)was increased and the peak of n-acetyl aspartic acid(NAA)was locally decreased.DTI showed a de crease of white matter fiber bundle and fractional anisotropy(FA)in the lateral posterior horn and the corpus callosum compression area.Gene sequencing: ABCD1 gene mutations were found in all 6 patie nts,and the mutation sites were different.According to the prediction o f Mutation Taster,Polyphen-2 and SIFT,they were pathogenic mutation s.Treatment and follow-up: 6 patients were treated with glucocorticoidreplacement.Cases 1,3 and 5 underwent HSCT.Case 6 was suppleme nted with Lorenzo's oil(LO).Cases 1 died,cases 3 and 4 progressed rapidly,cases 2,5 and 6 were stable.Genetic counseling: It is recommended that cases 3 and 4 families prepare for second pregnancy and rely on pre-implantation genetic diagn osis technology to breed healthy fetuses.It is suggested that in case 6 women with normal ABCD1 gene match,they can give birth to normal boys,and girls should be 50% normal and 50% heterozygotes.Conclusion:1.X-ALD males are more common and the rate of misdiagnosis is higher.Among them,the CCALD phenotype is the heaviest and the progress is the fastest.Early HSCT can improve the prognosis.2.Actively conducting genetic counseling can reduce the birth of children.