A report of atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum caused by a de novo mutation in tubulin beta 4A (TUBB4A) gene and literature review / 中华内科杂志

Objective To explore the clinical symptoms and neuroimaging features of a patient with atypical hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum (H-ABC) caused by a novel TUBB4A mutation.Methods We analyzed the clinical data, imaging features and the result of genetic testing of a case diagnosed as atypical H-ABC.Results The initial symptoms were progressive spasticity, mild cerebellar ataxia and mild cognitive impairment.MRI showed regional blurring of slight high signal on T2-weight and FLAIR image in white matter of the bilateral midbrain ventral, internal capsule, posteior horn of lateral ventricle and centrum semiovale, with normal bilateral cerebellar and caudoputamen nucleus.Compared with normal subjects of the same age and gender, hypometabolism was found by 18F-FDG-PET in brainstem, cerebellar and caudoputamen nucleus in the patient.Genetic testing revealed a de novo pathogenic exome missense heterozygous mutations c.70G>A in TUBB4A, which was not reported in the human gene mutation database (HGMDpro) and was assessed to be a pathogenic mutation by pathogenic mutation prediction software.Conclusions The diversity of TUBB4A gene mutations may cause different functional and/or structural impairment in subcortical white matter, cerebellar and caudoputamen nucleus, leading to atypical symptoms and neuroimaging features.Genetic testing for pathogenic mutation in TUBB4A gene is a key for the diagnosis of H-ABC.

Imaging of adult leukodystrophies / Imagem nas leucodistrofias do adulto

Leukodystrophies are genetically determined white matter disorders. Even though leukodystrophies essentially affect children in early infancy and childhood, these disorders may affect adults. In adults, leukodystrophies may present a distinct clinical and imaging presentation other than those found in childhood. Clinical awareness of late-onset leukodystrophies should be increased as new therapies emerge. MRI is a useful tool to evaluate white matter disorders and some characteristics findings can help the diagnosis of leukodystrophies. This review article briefly describes the imaging characteristics of the most common adult leukodystrophies.

Leucodistrofias são doenças geneticamente determinadas. Apesar das leucodistrofias afetarem principalmente crianças lactentes e infantes, estas doenças podem acometer a faixa etária adulta. Nos adultos, as leucodistrofias podem ter uma apresentação clínica e de imagem distinta daquela da infância. Um aumento na suspeita clínica de leucodistrofias com início tardio deve ocorrer associado ao aparecimento de novas alternativas terapêuticas. Este artigo de revisão descreve sumariamente as características de imagem nas leucodistrofias no adulto.

Adult-onset adrenoleukodystrophy presenting as a psychiatric disorder - MRI findings / Adrenoleucoistrofia de início tardio simulando doença psiquiátrica: relato de caso e revisão do assunto

A 35-year-old, previously healthy man presented psychiatric symptoms lasting four years, receiving treatmentwith neuroleptics. One year later he evolved with gait disequilibrium. After a further six months, cognitive symptoms werecharacterized with rapid evolution to a profound demented state. MRI showed signal changes in cerebral white matter andvery long-chain fatty acids were detected in blood.

Homem de 35 anos, previamente saudável, iniciou há quatro anos sintomas psiquiátricos, recebendo tratamentocom neurolépticos. Um ano após evoluiu com alterações do equilíbrio. Há seis meses apresentou distúrbios cognitivos, piorando rapidamente a um estado de profunda demência. RM do encéfalo revelou intensa alteração de sinal na substânciabranca cerebral e foram detectados ácidos graxos de cadeia muito longa no sangue.