Late-onset Leigh syndrome without delayed development in China:A case report

BACKGROUND Leigh syndrome(LS)is one of the most common mitochondrial diseases in infants and children.LS often manifests as early-onset with delayed phenotypic development.However,late-onset LS with normal development and white matter lesions in the brain is rarely reported,thereby highlighting the phenotypic variability of LS expression.CASE SUMMARY We report a 12-year-old boy who presented with an unusual late-onset and fulminant form of LS that is maternally inherited without developmental delay.The patient was admitted to the hospital with symptoms of ptosis and somnolence,and died within 2 mo.Analysis of peripheral blood leukocytes showed a homoplasmic m.9176T>C mutation in the patient.Magnetic resonance imaging also revealed lesions in bilateral white matter as well as symmetrical lesions in the basal ganglia and brain stem.The patient was diagnosed with LS.The patient was treated with vitamin C,vitamin D,and adenosine-triphosphate.The patient died within 2 mo of hospital admission.CONCLUSION LS can present in both infants and older children with different phenotypes.

Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome

Background Leigh syndrome is an inherited neurodegenerative disease that emerges in infancy and childhood and presents with a clinically heterogeneous variety of neuromuscular and non-neuromuscular disorders. It can result from the inheritance of mutations in either nuclear or mitochondrial DNA. In the current study, we performed a retrospective study in 65 patients in order to investigate the clinical and genetic characteristics of Leigh syndrome in Chinese patients. Methods Sixty-five unrelated cases （35 men and 30 women） who were hospitalized in the past 12 years were reviewed. Diagnosis was based on both the clinical presentation and the characteristic neuropathologic findings of bilateral symmetric necrotizing lesions in the basal ganglia and brain stem as detected using cranial computed tomography （CT） scan or magnetic resonance imaging （MRI）. The differential diagnosis of organic acidurias and fatty acid IS-oxidation defects were performed. Specific point mutations and deletions in mitochondrial DNA （T8993G, T8993C, T9176C, A8344G, A3243G） were screened by PCR-restriction analysis and Southern blot. The SURF1 gene was sequenced. Skeletal muscle biopsies were performed in 17 （26.2%） of the patients. The diagnosis was confirmed by autopsy in 6 （9.2%） patients. Results The patients had various forms of metabolic encephalomyopathy. Filly-nine （90.8%） of the patients had the typical neuroradiological features of Leigh syndrome, including symmetrical necrotizing lesions scattered within the basal ganglia, thalamus and brain stem. Twenty （30.8%） patients were confirmed by genetic, biochemical analysis and autopsy. Specific point mutations in mitochondrial DNA were found in 5 cases （7.7%）. Of these, the A8344G mutation was detected in 2 patients. The T8993G T8993C, and A3243G point mutations were identified in 3 other patients, respectively. SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 （12.3%） families by DNA sequencing. A G604C mutation was identified in 6 （9.2%） patients. The genotypes of 52 patients remained unknown. Conclusions Leigh syndrome presents as a diverse array of clinical features and can result from specific mutations in nuclear or mitochondrial DNA. In this study, SURF1 mutations associated with cytochrome c oxidase deficiency were identified in 8 （12.3%） out of 65 patients with Leigh syndrome. It indicates that SURF1 mutations might be a common cause of Leigh syndrome in China. The etiology of Leigh syndrome in Chinese patients represents a persistent challenge to clinicians.