Abstract
Infantile Neuro axonal Dystrophy (INAD), is a rare inherited neurological disorder which affects nerve axons causing progressive loss of mental skills, muscular control and vision. The authors present a case of 5.8-y-old girl with INAD who was diagnosed after Next Generation Sequencing (NGS). She was born to a non-consanguineous couple and presented with hypotonia, developmental delay followed by neuroregression and nystagmus after 2 years of age. On examination, bilateral horizontal nystagmus and normal head circumference were noted. Brain MRI showed cerebellar atrophy and altered signal intensities in bilateral globus pallidi and thalami. Magnetic resonance spectroscopy (MRS) showed elevation of lactate. Metabolic testing with Tandem Mass Spectrometry (TMS) and Gas Chromatography Mass Spectrometry (GC-MS) were normal. Mitochondrial disorder was suspected in view of clinical presentation, increased lactate and neuro-imaging suggestive of Leigh syndrome. Mitochondrial Leigh mutations and SURF1 gene sequencing yielded normal results. Lack of a clear diagnosis led to performance of NGS using panel of about 514 genes. A homozygous novel mutation at position c.2277-1G>C in PLA2G6 gene presumed to give rise to altered splicing, was detected, thus confirming the diagnosis of INAD. This report provides evidence of the usefulness of NGS technology as a quick and accurate diagnostic tool for an otherwise complicated genetic disease. To the authors knowledge, this is the first case report with mutations in PLA2G6 gene from India.
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Acknowledgments
The authors acknowledge the important contributions of their colleagues, Dr Ratna Puri, Dr Sudha Kohli and others for helping in clinical and molecular work up of the case.
Contributions
MG: Wrote the manuscript; SBM: Managed the case and wrote the manuscript; SK, EF and CS: Performed NGS and provided molecular confirmation; RS: Helped in molecular studies other than NGS; ICV: Provided critical comments and important intellectual inputs. SBM will act as guarantor of the manuscript.
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Goyal, M., Bijarnia-Mahay, S., Kingsmore, S. et al. Molecular Diagnosis of Infantile Neuro axonal Dystrophy by Next Generation Sequencing. Indian J Pediatr 82, 474–477 (2015). https://doi.org/10.1007/s12098-014-1608-z
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DOI: https://doi.org/10.1007/s12098-014-1608-z