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Lookup NU author(s): Dr Charlotte Alston, Professor Robert Taylor
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The diagnosis of pediatric metabolic disease is complicated and markers of dysfunction are often key in directing appropriate genetic testing. We present a 4-year-old girl with developmental regression following an episode of chicken pox at 7 months. She lost her ability to sit, roll over, or babble. Investigations revealed high plasma lactate at 3.7 mmol/L (normal: < 2 mmol/L). Magnetic resonance imaging of brain at 12 months showed cystic leukoencephalopathy with sparing of basal ganglia, brain stem, and cerebellum. At 16 months, she made developmental progress, spoke a few single words, and was standing with support. Repeat neuroimaging showed the white matter to be more atrophic with well-delineated cysts in the parietal white matter. The clinicoimaging pattern was suspicious of a mitochondrial disorder and a previously reported pathogenic NDUFV1 mutation, predicted to result in mitochondrial complex I deficiency, and was subsequently confirmed by molecular genetic analysis. Coincidentally, she had raised oxalate and glycolate on repeated urine examination with raised urine oxalate: creatinine ratio. Genetic testing confirmed a pathological mutation in AGXT, consistent with primary hyperoxaluria type 1. NDUFV1 mutations result in variable phenotypes including Leigh syndrome, infantile lactic acidosis, cardiomyopathy, leukoencephalopathy, and the majority are described to be progressive and rapidly fatal in some cases. After the initial episode and now aged 4 years, our index case continues to make developmental progress without further episodes of regression, although speech and language delay persists. This case helps broaden our understanding of genotype-phenotype correlations associated with recessively inherited NDUFV1 mutations and highlights that they can be associated with less severe phenotypes. Moreover, there may be coexisting conditions, particularly in consanguineous pedigrees, which careful analysis of their clinical and biochemical data may allude to.
Author(s): Silwal A, Morris A, Warren D, Vadlamani G, Alston CL, Taylor RW
Publication type: Article
Publication status: Published
Journal: Journal of Pediatric Neurology
Year: 2016
Volume: 14
Issue: 3
Pages: 126-132
Print publication date: 01/09/2016
Online publication date: 01/06/2016
Acceptance date: 09/04/2016
ISSN (print): 1304-2580
ISSN (electronic): 1305-0613
Publisher: Georg Thieme Verlag
URL: https://doi.org/10.1055/s-0036-1584303
DOI: 10.1055/s-0036-1584303
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