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Year : 2019  |  Volume : 14  |  Issue : 3  |  Page : 175-176

Phenotype of NDUFV1-related disease

1 Krankenanstalt Rudolfstiftung, Vienna, Austria
2 Pasteur Institute of Tunis, University of Tunis El Manar and Genomics Platform, Tunis, Tunisia

Date of Submission12-Aug-2018
Date of Decision12-Aug-2018
Date of Acceptance08-Aug-2019
Date of Web Publication27-Sep-2019

Correspondence Address:
Dr. Josef Finsterer
Krankenanstalt Rudolfstiftung, Postfach 20, 1180 Vienna
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_124_18

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How to cite this article:
Finsterer J, Zarrouk-Mahjoub S. Phenotype of NDUFV1-related disease. J Pediatr Neurosci 2019;14:175-6

How to cite this URL:
Finsterer J, Zarrouk-Mahjoub S. Phenotype of NDUFV1-related disease. J Pediatr Neurosci [serial online] 2019 [cited 2020 Aug 10];14:175-6. Available from: http://www.pediatricneurosciences.com/text.asp?2019/14/3/175/267979

With interest we read the article by Incecik et al.[1] about a 10-year-old boy, born to consanguineous parents, with late-onset Leigh syndrome due to the variant c.1268C>T in the NDUFV1 gene who initially presented with gait ataxia. We have the following comments and concerns.

Leigh syndrome is characterized by symmetric T2-hyperintensities of the basal ganglia, the brainstem, or the cerebellum.[2] However, Figure 1 of the case report shows asymmetric hyperintensity of the caput of the caudate nucleus.[1] Did hyperintensities of the caudate nucleus become bilaterally symmetric during follow-up?

The patient presented with marked cerebellar signs (horizontal nystagmus, ataxic gait, dysarthria, dysmetria, dysdiadochokinesia, and bilateral intention tremor).[1] Since Figure 1 does show the cerebellum properly, it would be interesting to know if there was cerebellar atrophy or other cerebellar lesions on imaging? Was there involvement of the cerebellar cortex or the cerebellar nuclei?

It would be interesting to know why the NDUFV1 gene was tested. Did the authors apply exome sequencing or did they apply a targeted, single-gene approach? Since the parents were obviously asymptomatic, the trait of inheritance is most likely autosomal recessive. Did any of the two parents or both carry the mutation in the NDUFV1 gene of the index case?

Mutations in NDUFV1 are usually associated with deficiency of complex I of the respiratory chain. Were biochemical investigations of the muscle homogenate or another tissue carried out and was complex I deficiency detected?

Since Leigh syndrome is a progressive disease in the majority of the cases, it would be interesting to know for how long the patient was followed up and if there was progression of the clinical, radiologic, or spectroscopic findings. Did the patient develop epilepsy, spasticity, insomnia, tremor, dystonia, personality change, myopathy, and visual impairment, as has been previously reported in association with NDUFV1 mutations [Table 1].
Table 1: Phenotypic manifestations of NDUFV1 mutations

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Nothing is reported about any therapeutic intervention.[1] Did the patient receive coenzyme-Q, riboflavin,[3] a ketogenic diet,[4] or L-carnitine and was any of these measures effective in the index case? Which was the long-term outcome of the patient?

In conclusion, this interesting case could be more meaningful if clinical and genetic data of the consanguineous parents would have been provided, if biochemical investigations would have been carried out, if imaging data of the cerebellum would have been provided, and if applied therapeutic interventions would have been discussed.[9]

   References Top

Incecik F, Herguner OM, Besen S, Bozdoğan ST, Mungan NO. Late-onset Leigh syndrome due to NDUFV1 mutation in a 10-year-old boy initially presenting with ataxia. J Pediatr Neurosci 2018;13:205-7.  Back to cited text no. 1
[PUBMED]  [Full text]  
Finsterer J. Leigh and Leigh-like syndrome in children and adults. Pediatr Neurol 2008;39:223-35.  Back to cited text no. 2
Bénit P, Chretien D, Kadhom N, de Lonlay-Debeney P, Cormier-Daire V, Cabral A, et al. Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency. Am J Hum Genet 2001;68:1344-52.  Back to cited text no. 3
Laugel V, This-Bernd V, Cormier-Daire V, Speeg-Schatz C, de Saint-Martin A, Fischbach M. Early-onset ophthalmoplegia in Leigh-like syndrome due to NDUFV1 mutations. Pediatr Neurol 2007;36:54-7.  Back to cited text no. 4
Wadhwa Y, Rohilla S, Kaushik JS. Cystic Leucoencephalopathy in NDUFV1 Mutation. Indian J Pediatr 2008.  Back to cited text no. 5
Zafeiriou DI, Rodenburg RJ, Scheffer H, van den Heuvel LP, Pouwels PJ, Ververi A, 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.  Back to cited text no. 6
Lal D, Becker K, Motameny S, Altmüller J, Thiele H, Nürnberg P, et al. Homozygous missense mutation of NDUFV1 as the cause of infantile bilateral striatal necrosis. Neurogenetics 2013;14:85-7.  Back to cited text no. 7
Baertling F, Sánchez-Caballero L, van den Brand MAM, Distelmaier F, Janssen MCH, Rodenburg RJT, et al. A Heterozygous NDUFV1 Variant Aggravates Mitochondrial Complex I Deficiency in a Family with a Homoplasmic ND1 Variant. J Pediatr 2018;196:309-313.e3.  Back to cited text no. 8
Schuelke M, Smeitink J, Mariman E, Loeffen J, Plecko B, Trijbels F, et al. Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy. Nat Genet 1999;21:260-1.  Back to cited text no. 9


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