TUBB4A-related hypomyelinating leukodystrophy: New insights from a series of 12 patients. (March 2016)

• Record Type: Journal Article
• Authors: Tonduti, Davide; Aiello, Chiara; Renaldo, Florence; Dorboz, Imen; Saaman, Simon; Rodriguez, Diana; Fettah, Houda; Elmaleh, Monique; Biancheri, Roberta; Barresi, Sabina; Boccone, Loredana; Orcesi, Simona; Pichiecchio, Anna; Zangaglia, Roberta; Maurey, Hélène; Rossi, Andrea; Boespflug-Tanguy, Odile; Bertini, Enrico
• Is Part Of: European journal of paediatric neurology. Volume 20:Number 2(2016:Mar.)
• Page Start: 323
• Page End: 330
• Publication Date: 2016-03
• Subjects: TUBB4A -- Hypomyelination -- Leukodystrophy -- H-ABC -- Cerebellar -- Atrophy; Pediatric neurology -- Periodicals; Nervous System Diseases -- Periodicals; Child -- Periodicals; Infant -- Periodicals; Neurologie pédiatrique -- Périodiques; Pediatric neurology; Electronic journals; Periodicals; Electronic journals; 618.928
• DOI: 10.1016/j.ejpn.2015.11.006
• Languages: English
• ISSNs: 1090-3798

Abstract

Abstract: Background: Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) was first described in 2002. After the recent identification of TUBB4A mutation as the genetic basis of the disease, the clinical and neuroimaging phenotype related to TUBB4A mutations expanded, ranging from primary dystonia type 4 with normal MRI to severe H-ABC cases. Patients and methods: The study included patients referred to us for an unclassified hypomyelinating leukodystrophy. We selected patients with deleterious heterozygous TUBB4A mutations. Molecular analysis of TUBB4A was performed on genomic DNA extracted from peripheral blood. Results: The series included 12 patients (5 females and 7 males). Five patients carried the common mutation c.745G > A (p.Asp249Asn), while the remaining harbored different mutations. Three new mutations were found in 5 patients. Clinical and neuroimaging observations are described. A clear correlation between the clinical presentation and the genotype seems to be absent in our group of 12 patients. Conclusions: TUBB4A -mutated patients manifest a comparable clinical and neuroimaging picture but they can differ from each other in terms of rate of disease progression. Extrapyramidal signs can be absent in the first stages of the disease, and a careful evaluation of MRI is fundamental to obtain the final diagnosis. From a therapeutic perspective a trial withl -dopa should be considered in all patients presenting extrapyramidal symptoms. Highlights: TUBB4A -mutated patients show a similar features but they can differ from each other in terms of disease progression rate. Clinical phenotype is probably modulated by unknown genetic factors. Extrapyramidal signs can be absent in the first phases of the disease. A careful evaluation of MRI is fundamental, particularly in patients without the classical radiological pattern. A trial withl -dopa should be considered in all patients presenting extrapyramidal symptoms.