Mitochondrial oxidative phosphorylation disorders in children: Phenotypic, genotypic and biochemical correlations in 85 patients from South India.
Mitochondrial oxidative phosphorylation (OXPHOS) disorders account for a variety of neuromuscular disorders in children. In this study mitochondrial respiratory chain enzymes were assayed in muscle tissue in a large cohort of children with varied neuromuscular presentations from June 2011 to December 2013. The biochemical enzyme deficiencies were correlated with the phenotypes, magnetic resonance imaging, histopathology and genetic findings to reach a final diagnosis. There were 85 children (mean age: 6.9±4.7years, M:F:2:1) with respiratory chain enzyme deficiency which included: isolated complex I (n=50, 60%), multiple complexes (n=24, 27%), complex IV (n=8, 9%) and complex III deficiencies (n=3, 4%). The most common neurological findings were ataxia (59%), hypotonia (59%) and involuntary movements (49%). A known mitochondrial syndrome was diagnosed in 27 (29%) and non-syndromic presentations in 57 (71%). Genetic analysis included complete sequencing of mitochondrial genome, SURF1, POLG1&2. It revealed variations in mitochondrial DNA (n=8), SURF1 (n=5), and POLG1 (n=3). This study, the first of its kind from India, highlights the wide range of clinical and imaging phenotypes and genetic heterogeneity in children with mitochondrial oxidative phosphorylation disorders.
Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Kothari
K
Sonam
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Electronic address: drpsbindu@yahoo.co.in.
Parayil Sankaran
PS
Bindu
Department of Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
M M
MM
Srinivas Bharath
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Periyasamy
P
Govindaraj
Department of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Narayanappa
N
Gayathri
Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Hanumanthapura R
HR
Arvinda
Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Shwetha
S
Chiplunkar
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Madhu
M
Nagappa
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Sanjib
S
Sinha
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Nahid Akhtar
NA
Khan
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Vandana
V
Nunia
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Arumugam
A
Paramasivam
CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
Kumarasamy
K
Thangaraj
Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Arun B
AB
Taly
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D030401:Cytochrome-c Oxidase Deficiency; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D042967:Electron Transport Complex I / Q000172:deficiency; D014450:Electron Transport Complex III / Q000172:deficiency; D003576:Electron Transport Complex IV; D005260:Female; D054629:Genome, Mitochondrial; D006651:Histocytochemistry; D006801:Humans; D007194:India; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008659:Metabolic Diseases / Q000235:genetics* / Q000473:pathology*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000235:genetics; D009132:Muscles / Q000473:pathology; D009468:Neuromuscular Diseases / Q000235:genetics* / Q000473:pathology*; D010085:Oxidative Phosphorylation; D017422:Sequence Analysis, DNA
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C092928:Surf-1 protein; D003576:Electron Transport Complex IV; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human; C544932:POLG2 protein, human; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III
Oxidative phosphorylation disorders; POLG1; SURF; mtDNA