Clinical, Neuroimaging, and Pathological Analyses of 13 Chinese Leigh Syndrome Patients with Mitochondrial DNA Mutations.

Xiao-lin YU; Chuan-zhu Yan; Kun-qian JI; Peng-fei Lin; Xue-bi XU; Ting-jun Dai; Wei LI; Yu-ying Zhao

Return

Clinical, Neuroimaging, and Pathological Analyses of 13 Chinese Leigh Syndrome Patients with Mitochondrial DNA Mutations.

Author: Xiao-Lin YU ^{1
,

2
,

3} ; Chuan-Zhu YAN ^{4
,

5
,

6} ; Kun-Qian JI ⁷ ; Peng-Fei LIN ⁷ ; Xue-Bi XU ⁷ ; Ting-Jun DAI ⁷ ; Wei LI ⁷ ; Yu-Ying ZHAO ⁷
Author Information

1. Department of Geriatrics Medicine
2. Department of Neurology, Research Institute of Neuromuscular and Neurodegenerative Diseases
3. Key Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
4. Department of Neurology, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital, Jinan, Shandong 250012
5. Mitochondrial Medicine Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao, Shandong 266035
6. Brain Science Research Institute, Shandong University, Jinan, Shandong 250012, China.
7. Department of Neurology, Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital, Shandong University, Jinan, Shandong 250012, China.
Publication Type:Journal Article
Keywords: Clinical Features; Leigh Syndrome; Mitochondrial DNA; Neuroimaging; Pathology
MeSH: Child; Child, Preschool; Creatine Kinase; blood; Cytochrome-c Oxidase Deficiency; DNA, Mitochondrial; genetics; Fasting; blood; cerebrospinal fluid; Female; Humans; Infant; Lactic Acid; blood; cerebrospinal fluid; Leigh Disease; diagnostic imaging; genetics; Magnetic Resonance Imaging; Male; Mutation; genetics; Neuroimaging; methods
From: Chinese Medical Journal 2018;131(22):2705-2712
CountryChina
Language:English
Abstract: Background:Leigh syndrome (LS) is a rare disease caused by mitochondrial defects and has high phenotypic and genotypic heterogeneity. We analyzed the clinical symptoms, neuroimaging, muscular histopathology, and genotypes of 13 Chinese LS patients with mitochondrial DNA (mtDNA) mutations.
Methods:Mutations in mtDNA were identified by targeted sequencing. The brain imaging features on magnetic resonance imaging (MRI) were analyzed. The levels of lactate in fasting blood and cerebrospinal fluid (CSF) were routinely tested. The levels of urinary organic acids, plasma amino acids, and acylcarnitines were examined with gas chromatography-mass spectrometry and tandem mass spectrometry. The histopathological traits of skeletal muscles were analyzed under microscope.
Results:Among 13 patients, mutations of MT-NDs (n = 8) and MT-ATP6 (n = 4) genes were most common. Strabismus (8/13), muscle weakness (8/13), and ataxia (5/13) were also common, especially for the patients with late-onset age after 2 years old. However, respiratory distress was common in patients with early-onset age before 2 years old. The most frequently affected brain area in these patients was the brain stem (12/13), particularly the dorsal part of midbrain, followed by basal ganglia (6/13), thalamus (6/13), cerebellum (5/13), and supratentorial white matter (2/13). Besides, the elevated lactate levels in CSF (6/6) were more common than those in serum (7/13). However, the analysis of abnormal plasma amino acid and urinary organic acid showed limited results (0/3 and 1/4, respectively). Muscular histopathology showed mitochondrial myopathy in the three late-onset patients but not in the early-onset ones.
Conclusions:Noninvasive genetic screening is recommended for mtDNA mutations in MT-NDs and MT-ATP6 genes in patients with ophthalmoplegia, muscle weakness, ataxia, and respiratory disorder. Furthermore, the lactate detection in CSF and the brain MRI scanning are suggested as the diagnosis methods for LS patients with mtDNA mutations.