P144 – 3081: A new mutation for pontocerebellar hypoplasia type 6

Abstract

Objective Pontocerebellar hypoplasia is part of a group of autosomal recessive neurodegenerative disorders with perinatal onset. The rarity and genetic heterogeneity of this group of pathologies make diagnosis a challenge. Cerebellar hypoplasia is usually present with variable atrophy of cerebellum, ventral pons and neocortex, ventriculomegaly and microcephaly. At least ten subtypes of pontocerebellar hypoplasia have been identified. The type 6 is associated with encephalopathy, hypotonia, apnea and seizures difficult to control. The gene involved is the RAR2 that encodes mitochondrial protein arginil-TRNA sintetase2. The goal of this work is present a new mutation of this entity. Methods Herein we present two clinical cases of a new mutation in the gene of Pontocerebellar hypoplasia type 6, and briefly review the pathogenesis. Results Two siblings of a co-sanguineous family developed feeding problems within the first days after birth. A generalized hypotonia that evolved to hypertonia and pyramidal signs during the first month. They both had in the first two-weeks of life seizures that progressed to a refractory epilepsy, general deterioration and apneas, and utterly dying before 12 months. Lab tests were normal (Transferrin cdt, VLFA chain, sialic acid, amino-acids and organic-acids chromatography, pipecolic acid, purines and pyrimidines). The CSF's lactate was slightly elevated but a dysfunction of pyruvate desidrogenase could never be proved, and CSF's glicose, neurotransmitters and folate were normal. The aCGH was normal. Muscle biopsy with normal pattern. The MRI showed hypoplasia of corpus callosum and cerebellum. Due to lack of diagnosis, exome sequence was performed revealing homozygous mutation (c.451+4A>G) in gene RARS2 that leads to a change in position +4 of intron 6, which can be presumed to affect the splincing. Conclusion This case illustrates, the clinical presentation and evolution of pontocerebellar hypoplasia type 6. The authors emphases the importance of exome sequence, in order to achieve a diagnosis.