Cystic Leucoencephalopathy in NDUFV1 Mutation

  • Yamini Wadhwa
  • Seema Rohilla
  • Jaya Shankar Kaushik
Clinical Brief


Complex I deficiency is one of the most common mitochondrial respiratory chain defect. This deficiency of oxidative phosphorylation results from mutation in nuclear and mitochondrial DNA. Mutations in NDUFV1 (Flavin binding subunit of Respiratory complex 1) results in neurological manifestations including Leigh syndrome and leucoencephalopathy. The authors report a one-year-old boy with history of regression of motor milestones following a trivial fall from the bed. His magnetic resonance imaging revealed diffuse, cystic leucoencephalopathy involving corpus callosum and periventricular white matter. Clinical features and radiological findings may resemble those of vanishing white matter disease. Next generation sequencing revealed likely compound heterozygous missense pathogenic variant in exon 8 of NDUFV1 gene [c.1156C > C/T (p.Arg386Cys)] and possibly novel splice site variation in intron 2 of NDUFV1 gene (c.155 + 1G > G/A). NDUFV1 related leucoencephalopathy must be considered among those presenting with sudden onset of motor regression with neuroimaging correlate of diffuse cystic leucodystrophy.


Mitochondrial complex I deficiency NDUFV1 mutation Mitochondrial diseases White matter 



The authors acknowledge the help of Dr. Divya Gupta, for her genetic input in the manuscript.


JSK: Patient management. YW, SR, JSK: Drafting the manuscript and review of literature; JSK, SR: Critical review of the manuscript for intellectual content and final approval of the version to be published; SR: Critical radiological input. JSK: Clinician-in-charge, critical review of the manuscript for intellectual content, final approval of the version to be published and will act as guarantor for the paper.

Compliance with Ethical Standards

Conflict of Interest



  1. 1.
    Bugiani M, Invernizzi F, Alberio S, et al. Clinical and molecular findings in children with complex I deficiency. Biochim Biophys Acta. 2004;1659:136–47.CrossRefPubMedGoogle Scholar
  2. 2.
    Ortega-Recalde O, Fonseca DJ, Patiño LC, et al. A novel familial case of diffuse leukodystrophy related to NDUFV1 compound heterozygous mutations. Mitochondrion. 2013;13:749–54.CrossRefPubMedGoogle Scholar
  3. 3.
    Vilain C, Rens C, Aeby A, et al. A novel NDUFV1 gene mutation in complex I deficiency in consanguineous siblings with brainstem lesions and Leigh syndrome. Clin Genet. 2012;82:264–70.CrossRefPubMedGoogle Scholar
  4. 4.
    Björkman K, Sofou K, Darin N, et al. Broad phenotypic variability in patients with complex I deficiency due to mutations in NDUFS1 and NDUFV1. Mitochondrion. 2015;21:33–40.CrossRefPubMedGoogle Scholar
  5. 5.
    Lal D, Becker K, Motameny S, et al. Homozygous missense mutation of NDUFV1 as the cause of infantile bilateral striatal necrosis. Neurogenetics. 2013;14:85–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Marin SE, Mesterman R, Robinson B, Rodenburg RJ, Smeitink J, Tarnopolsky MA. Leigh syndrome associated with mitochondrial complex I deficiency due to novel mutations in NDUFV1 and NDUFS2. Gene. 2013;516:162–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Ren CH, Fang F, Cheng H, et al. [Progressive cavitating leukoencephalopathy: four cases and literatures review]. Zhonghua Er Ke Za Zhi. 2017;55:283–7.PubMedGoogle Scholar
  8. 8.
    Breningstall GN, Shoffner J, Patterson RJ. Siblings with leukoencephalopathy. Semin Pediatr Neurol. 2008;15:212–5.CrossRefPubMedGoogle Scholar
  9. 9.
    Zafeiriou DI, Rodenburg RJT, Scheffer H, et al. MR spectroscopy and serial magnetic resonance imaging in a patient with mitochondrial cystic leukoencephalopathy due to complex I deficiency and NDUFV1 mutations and mild clinical course. Neuropediatrics. 2008;39:172–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Finsterer J, Mahjoub SZ. Leucoencephalopathies in mitochondrial disorders: clinical and MRI findings. J Neuroimaging. 2012;22:e1–11.CrossRefPubMedGoogle Scholar
  11. 11.
    Koene S, Rodenburg RJ, van der Knaap MS, et al. Natural disease course and genotype-phenotype correlations in complex I deficiency caused by nuclear gene defects: what we learned from 130 cases. J Inherit Metab Dis. 2012;35:737–47.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Schuelke M, Smeitink J, Mariman E, et al. Mutant NDUFV1 subunit of mitochondrial complex I causes leucodystrophy and myoclonic epilepsy. Nat Genet. 1999;21:260–1.CrossRefPubMedGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2018

Authors and Affiliations

  • Yamini Wadhwa
    • 1
  • Seema Rohilla
    • 1
  • Jaya Shankar Kaushik
    • 2
  1. 1.Department of RadiodiagnosisPt B D Sharma Post Graduate Institute of Medical SciencesRohtakIndia
  2. 2.Pediatric Neurology Services, Department of PediatricsPt B D Sharma Post Graduate Institute of Medical SciencesRohtakIndia

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