Lookup NU author(s): Marina Bartsakoulia,
Professor Rita Horvath
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background: Pontocerebellar hypoplasia type 6 (PCH6) is a mitochondrial disease caused by mutations in the RARS2 gene. RARS2 encodes mitochondrial arginyl transfer RNA synthetase, an enzyme involved in mitochondrial protein translation. A total of 27 patients from 14 families have been reported so far. Characteristic clinical features comprise neonatal lactic acidosis, severe encephalopathy, intractable seizures, feeding problems and profound developmental delay. Most patients show typical neuroradiologic abnormalities including cerebellar hypoplasia and progressive pontocerebellar atrophy.Methods: We describe the clinical, biochemical and molecular features of 2 siblings with a novel homozygous mutation in RARS2. Both patients presented neonatally with lactic acidosis. While the older sibling had severe neurological symptoms with microcephaly, seizures and developmental delay, the younger patient was still neurologically asymptomatic at the age of 2 months.Results: MRI studies in both children lacked pontocerebellar involvement. The expression of the OXPHOS complex proteins was decreased in both patients, whereas oxygen consumption was increased.Conclusions: Characteristic neuroradiological abnormalities of PCH6 such as vermis and cerebellar hypoplasia and progressive pontocerebellar atrophy may be missing in patients with RARS2 mutations. RARS2 testing should therefore also be performed in patients without pontocerebellar hypoplasia but otherwise typical clinical symptoms.
Author(s): Luhl S, Bode H, Schlotzer W, Bartsakoulia M, Horvath R, Abicht A, Stenzel M, Kirschner J, Grunert SC
Publication type: Article
Publication status: Published
Journal: Orphanet Journal of Rare Diseases
Online publication date: 21/10/2016
Acceptance date: 11/10/2016
Date deposited: 08/12/2016
ISSN (print): 1750-1172
Publisher: BioMed Central Ltd.
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