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Case Reports
. 2022 May 18:10:812408.
doi: 10.3389/fped.2022.812408. eCollection 2022.

NDUFAF6-Related Leigh Syndrome Caused by Rare Pathogenic Variants: A Case Report and the Focused Review of Literature

Jaewon Kim  1 , Jaewoong Lee  2 , Dae-Hyun Jang  1
Affiliations
Case Reports

NDUFAF6-Related Leigh Syndrome Caused by Rare Pathogenic Variants: A Case Report and the Focused Review of Literature

Jaewon Kim et al. Front Pediatr. .

Abstract

Leigh syndrome is a neurodegenerative disorder that presents with fluctuation and stepwise deterioration, such as neurodevelopmental delay and regression, dysarthria, dysphagia, hypotonia, dystonia, tremor, spasticity, epilepsy, and respiratory problems. The syndrome characteristically presents symmetric necrotizing lesions in the basal ganglia, brainstem, cerebellum, thalamus, and spinal cord on cranial magnetic resonance imaging. To date, more than 85 genes are known to be associated with Leigh syndrome. Here, we present a rare case of a child who developed Leigh syndrome due to pathogenic variants of NDUFAF6, which encodes an assembly factor of complex I, a respiratory chain subunit. A targeted next-generation sequencing analysis related to mitochondrial disease revealed a missense variant (NM_152416.4:c.371T > C; p.Ile124Thr) and a frameshift variant (NM_152416.4:c.233_242del; p.Leu78GInfs*10) inherited biparentally. The proband underwent physical therapy and nutrient cocktail therapy, but his physical impairment gradually worsened.

Keywords: Leigh syndrome; NDUFAF6; complex I deficiency; mitochondrial disease; neurodegenerative disorder.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Brain MRI showing high signal intensity on T2-weighted imaging (A. axial, B. coronal) and diffusion-weighted imaging (C), apparent diffusion coefficient (D), and fluid-attenuated inversion recovery (E) images with low signal intensity on T1-weighted imaging (F) in the bilateral putamen. Arrowheads indicate the lesions.
FIGURE 2
FIGURE 2
Brain MR spectroscopy showing increased lipid and lactate in the lesions. Normal patterns outside lesions (A), elevated lipids (white arrow) (B), and elevated lactate in both putamen (arrowhead) (C,D).
FIGURE 3
FIGURE 3
(A) Pedigree of the family. Arrow indicates the proband. (B) Chromatographs of NDUFAF6. The proband had a missense variant (c.371T > C) from the mother and a frameshift variant (c.233_242del) from the father.
FIGURE 4
FIGURE 4
Genetic structure of NDUFAF6. Pathogenic variants previously reported are indicated by arrows.
See this image and copyright information in PMC

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