[P1-191] Hypomyelinating Leukodystrophy with TUBB4A Mutation: Report of 2 Patients in a Chinese Family and Literature Review
Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) was first described in 2002. The genetic basis is clear after the identification of TUBB4A mutation. The clinical phenotype varies, ranging from primary dystonia type 4 with normal MRI to severe H-ABC cases. We identified 2 patients in a Chinese family. The index case (daughter) presented with seizures at 1 year of age, characterized by generalized tonic clonic seizures (GTCS), lasting 1-2 min, frequently relapsed after onset, totally 11 seizures in the first year after seizure onset. Oxcarbazepine was prescribed, with seizure free for 1year; followed by a relapsed GTCS lasting 1 min. The perinatal history had nothing special; and developmental milestones had been normal. Her MRI showed white matter hypomyelination, with cerebellar atrophy. EEG revealed no abnormalities. Her 27 years old father is slightly mental retarded, with mild movement disturbance since his infancy. The progress had been not evident, being able to do light house work now. CT scan of the father in 2009 showed mild cerebellar atrophy. Her mother and younger brother(2 year old) are normal. Next generation sequencing of the daughter identified heterozygous mutation of TUBB4A (c.533C>T). Sanger sequencing was performed on the father and demonstrated the same heterozygous mutation of TUBB4A; whereas her mother and brother are normal. Hypomyelinating leukodystrophy with TUBB4A Mutation is rare. Here we presented a Chinese pedigree, demonstrating a wild clinical spectrum of the disease: movement disturbances, cerebellar atrophy, seizures, as well as hypomyelination of the cerebrum. Related literatures will be reviewed.