A case of Leigh syndrome associated with respiratory chain complex I deficiency due to mitochondrial gene 13513G>A mutation / 中国当代儿科杂志

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs', cycle. Mitonchondrial complex I deficiency is a main cause of Leigh syndrome. In this study, a Chinese child with Leigh syndrome caused by 13513G>A mutation was reported. The proband was the first child of his parents. The previously healthy boy presented with generalized epilepsy at 12 years of age. When he visited Peking University First Hospital at 13 years of age, he had subacute loss of vision in two eyes and temporal defect of visual field in the left eye. He walked with a spastic gait. His blood lactate and pyruvate levels were elevated. Muscle biopsy showed mild lipid accumulation in muscle fiber. An electrocardiogram showed incomplete right bundle branch block. Brain magnetic resonance imaging showed bilateral, symmetrical lesions in the basal ganglia, supporting the diagnosis of Leigh syndrome. 13513G>A mutation was identified by gene analysis in the patient, which led to mitochondrial respiratory chain complex I deficiency. Multivitamins and L-carnitine were administered. At present, the patient is 16 years old and has progressive deterioration with significant muscle weakness and body weight loss. He is absent from school. He has no obvious retardation in intelligence. 13513G>A mutation was first identified by gene analysis in Chinese population with Leigh syndrome. This may be helpful in genetic counseling.

Leigh syndrome due to pyruvate dehydrogenase E1 alpha subunit gene mutation: a complicated and difficult case study / 中国当代儿科杂志

Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs' cycle. Deficiency of pyruvate dehydrogenase complex E1 alpha subunit (PDHA1) is the common cause of Leigh syndrome. In this study, one Chinese case of PDHA1 deficiency was reported. The patient was a boy with normal mental development, retarded motor development, general weakness, hypotonia and areflexia. Muscle histopathological findings suggested axonal peripheral neuropathy. Brain magnetic resonance imaging at 5 years of age revealed bilateral putamina lesions and periventricular white matter demyelination, supporting the diagnosis of Leigh syndrome. A C214T mutation in exon 3 of the PDHA1 gene was detected. After the treatment of thiamin, coenzyme Q10, Lcarnitine and carbohydrates-restricted diet, his movement ability improved significantly. At present, the patient is 8 years old and has normal school life. PDHA1 deficiency is an X-linked inherited metabolic disease, which shares various clinical manifestations and leads to difficult diagnosis. This patient predominately presented with progressive weakness and was diagnosed by gene analysis.

Clinical and laboratory survey of 65 Chinese patients with Leigh syndrome / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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 beta-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.</p><p><b>RESULTS</b>The patients had various forms of metabolic encephalomyopathy. Fifty-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.</p><p><b>CONCLUSIONS</b>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.</p>

MRI evaluation of cerebral perfusion change in pediatric patients with Leigh's syndrome / 中华放射学杂志

Objective To detect the change of cerebral perfusion in pediatric patients with Leigh's syndrome (LS)by using MR perfusion technique.Methods Twelve patients with Leigh's syndrome and thirteen normal children were scanned with the sequence of flow-sensitive alternating inversion recovery exempting separate T_1 measurement (FAIREST).Their relative cerebral blood flow(rCBF)values were obtained in regions of bilateral basilar nuclei and bilateral thalami.Student t-test was used to compare them between the two groups and receiver operating characteristic(ROC)curve analysis was carried out.Results Statistical analysis revealed significant difference between two groups in the regions of bilateral basilar nuclei and right thalamus(t =3.26,P =0.002;t =2.25 ,P =0.018 ;t =2.88 ,P =0.004,respectively).The rCBF values for LS group and control group were 0.432?0.158 and 0.619?0.125 for right basilar nuclear, 0.478?0.186 and 0.621?0.123 for left basilar nuclear,0.630?0.189 and 0.833?0.160 for right thalamus,respectively.The areas under the ROC curves were 0.833 and 0.756 for the rCBF of right and left basilar nuclear,respectively.Conclusion Relative CBF maps may reveal changes of cerebral blood flow in some specific brain regions in patients with Leigh's syndrome.It can provide additional information to the clinicians in the evaluation of the disease.