Humans ; Leigh Disease/therapy* ; Consensus ; Brain ; DNA, Mitochondrial

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.
Child, Preschool ; Diagnosis, Differential ; Humans ; Leigh Disease ; diagnosis ; genetics ; therapy ; Male ; Mutation ; Pyruvate Dehydrogenase (Lipoamide) ; genetics

Mitochondrial respiratory chain complex II deficiency is a rare documented cause of mitochondrial diseases. This study reported a case of Leigh syndrome due to isolated complex II deficiency. A boy presented with progressive weakness, motor regression and dysphagia after fever from the age of 8 months and hospitalized at the age of 10 months. Elevated blood levels of lactate and pyruvate were observed. Brain magnetic resonance image showed symmetrical lesions in the basal ganglia. Mitochondrial respiratory chain complex I-V activities in peripheral leukocytes were measured using spectrophotometric assay. Mitochondrial gene screening of common point mutations was performed. The complex II activity in the peripheral leukocytes decreased to 21.9 nmol/min per mg mitochondrial protein (control: 47.3±5.3 nmol/min per mg mitochondrial protein). The ratio of complex II activity to citrate synthase activity (22.1%) also decreased (control: 50.9%±10.7 %). No point mutation was found in mitochondrial DNA. The boy was diagnosed as Leigh syndrome due to isolated complex II deficiency. Psychomotor improvements were observed after the treatment. The patient is 22 months old and in a stable condition.
Diagnosis, Differential ; Electron Transport Complex II ; deficiency ; Humans ; Infant ; Leigh Disease ; diagnosis ; etiology ; therapy ; Male ; Mitochondrial Diseases ; complications

Leigh's syndrome, which is characterised by progressive neurodegeneration involving the brainstem and basal ganglia, belongs to a family of disorders classified as mitochondrial myopathies. It is most commonly transmitted by an autosomal recessive mode of inheritance, but can sometimes occur in a mitochondrial pattern. It typically presents during infancy with developmental delay and deterioration of brainstem function. Respiratory failure is the common cause of death and postoperative morbidity in patients with Leigh's disease. Herein, we report the case of a 17-year-old female patient with Leigh's syndrome who underwent general anaesthesia for a tracheostomy, which was performed in view of the patient's requirement for long-term ventilation and frequent toileting for secretions. Her respiratory complications included central hypoventilation secondary to brainstem involvement, and obstructive sleep apnoea due to obesity and muscle dystonia. She was hospitalised for acute respiratory decompensation secondary to hospital-acquired pneumonia. We review the anaesthetic implications of this disease and discuss its impact on preoperative, intraoperative and postoperative management.
Adolescent ; Anesthesia, General ; methods ; Anesthetics ; therapeutic use ; Dystonia ; pathology ; Female ; Humans ; Hypoventilation ; complications ; diagnosis ; Leigh Disease ; complications ; drug therapy ; Mitochondria ; pathology ; Postoperative Complications ; Sleep Apnea, Obstructive ; complications ; Ventilation

BACKGROUNDLeigh 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.

METHODSSixty-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.

RESULTSThe 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.

CONCLUSIONSLeigh 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.

Adolescent ; Child ; Child, Preschool ; Cytochrome-c Oxidase Deficiency ; genetics ; Female ; Humans ; Infant ; Infant, Newborn ; Leigh Disease ; genetics ; metabolism ; pathology ; therapy ; Male ; Membrane Proteins ; Mitochondrial Proteins ; Mutation ; Proteins ; genetics ; Retrospective Studies ; Treatment Outcome