Novel homozygous RARS2 mutation in two siblings without pontocerebellar hypoplasia - further expansion of the phenotypic spectrum.

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.

[Stent-assisted intracranial angioplasty: potentials and limitations of pre- and postinterventional CT angiography]. / Stentgestützte intrakranielle Angioplastie: Möglichkeiten und Grenzen der prä- und postinterventionellen CT-Angiografie.

PURPOSE: CT angiography (CTA) is a noninvasive technique for evaluating intracranial arterial stenoses and for following up on intracranial stents. We analyzed a series of patients to assess the capabilities of CTA with respect to preinterventional und postinterventional diagnostic imaging for stent-assisted intracranial angioplasty. MATERIALS AND METHODS: We examined 8 patients with 9 symptomatic intracranial arterial stenoses before and after stent placement with CTA. CT angiographies were compared to the periprocedural conventional angiography with regard to the quality of the visualization as well as the dimensions of the identified stenoses and the implanted stents. RESULTS: The extent of the preinterventional intracranial stenoses identified with CTA differed between -15% to + 12% from conventional angiography. In any case we were able to assess stent position, expansion, and perfusion with postinterventional CTA. The mean residual stenosis after stent placement was 33% (13 - 48%) measured with conventional angiography and it was accurately estimated with a difference of +/- 15% in 5 of 9 stents by CTA. 4 residual stenoses were underestimated or overestimated between -20% and + 26%. Further CTA controls of several patients showed good visualization of in-stent neointimal hyperplasia. CONCLUSION: CTA is useful for stent planning and follow-up of symptomatic intracranial stenoses. Intracranial stents and their lumina are adequately visualized by CTA, especially in vertebrobasilar vessels. However, residual stenosis and restenosis especially in the intracranial internal carotid artery and in the presence of calcified plaques may be incorrectly estimated by CTA. In case of doubt patients must undergo invasive angiography. In summary the use of CTA is a possibility for the primary follow-up of intracranial stents. It cannot generally prevent further diagnostics, but it is a potential method for reducing invasive angiography.