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Case Reports
. 2023 Oct 30:10:2329048X231210421.
doi: 10.1177/2329048X231210421. eCollection 2023 Jan-Dec.

A Case of Multiple Mitochondrial Dysfunctions Syndrome 4 with Novel ISCA2 Variants, Mimicking Post-Infectious Encephalitis

Hyungjin Chin  1 , Jaeso Cho  2 , Woo Joong Kim  1 , Soo Yeon Kim  2 , Byung Chan Lim  1 , Ki Joong Kim  1 , Jong Hee Chae  1   2
Affiliations
Case Reports

A Case of Multiple Mitochondrial Dysfunctions Syndrome 4 with Novel ISCA2 Variants, Mimicking Post-Infectious Encephalitis

Hyungjin Chin et al. Child Neurol Open. .

Abstract

ISCA2 loss of function leads to leukodystrophy and developmental regression (multiple mitochondrial dysfunctions syndrome 4 (MMDS4)). We present a first Korean case of MMDS4 presenting with rapid developmental regression and leukodystrophy after febrile episode, mimicking post-infectious encephalitis. The patient had displayed normal development until 12 months of age. At 13 months of age, one month after experiencing a post-vaccination fever, she quickly progressed to being unable to sit unassisted nor speak any words. Analysis of the cerebrospinal fluid (CSF) revealed lympho-dominant pleocytosis. Amino acid analysis of both the serum and CSF demonstrated elevated glycine exclusively in the CSF. Diffuse leukodystrophy was noted in the brain magnetic resonance image. Whole exome sequencing revealed compound heterozygous ISCA2 variants of c.166T>G, p.C56G and c.422A>C, p.Q141P. No evidence of mitochondrial disease other than bilateral optic atrophy was noted. In cases of early onset rapid developmental regression with leukodystrophy, MMDS4 should be considered.

Keywords: ISCA2; developmental regression; glycine; leukodystrophy; multiple mitochondrial dysfunctions syndrome 4.

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Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
A. Temporal changes of brain magnetic resonance image. (A, B, C) Fluid attenuated inversion recovery image. (a, b, c) Diffusion weighted image. (A, a) At initial presentation of 13 months of age. Bilateral leukodystrophy with diffusion restriction is found, involving corpus callosum. (B, b) At 16 months of age, after corticosteroid therapy, the extent of leukodystrophy and diffusion restriction improved. Interval atrophic change of brain is noted. (C, c) At 19 months of age, after genetic diagnosis, aggravated leukodystrophy extending to subcortical white matter, with subependymal cystic changes and diffusion restriction is shown. (D) Spectroscopy at 19 months of age shows no increase in lactate peak. B. Pathogenic ISCA2 variants reported to date (Reference sequence NM_194279). Homozygous variants are colored as brown, and compound heterozygous variants are colored as yellow.
See this image and copyright information in PMC

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