TUBB4A-related hypomyelinating leukodystrophy: New insights from a series of 12 patients

Davide Tonduti, Chiara Aiello, Florence Renaldo, Imen Dorboz, Simon Saaman, Diana Rodriguez, Houda Fettah, Monique Elmaleh, Roberta Biancheri, Sabina Barresi, Loredana Boccone, Simona Orcesi, Anna Pichiecchio, Roberta Zangaglia, Hélène Maurey, Andrea Rossi, Odile Boespflug-Tanguy, Enrico Bertini

Research output: Contribution to journalArticlepeer-review


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 with l-dopa should be considered in all patients presenting extrapyramidal symptoms.

Original languageEnglish
Pages (from-to)323-330
Number of pages8
JournalEuropean Journal of Paediatric Neurology
Issue number2
Publication statusPublished - Mar 1 2016


  • Atrophy
  • Cerebellar
  • H-ABC
  • Hypomyelination
  • Leukodystrophy
  • TUBB4A

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health


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