PURPOSE: Severe myoclonic epilepsy in infancy (SMEI) seems to be more common than realized, because it is often overlooked. In addition, the prognosis is poor despite of recent advances of antiepileptic treatment. This study is intended to provide better identification and treatment of SMEI by reviewing our experiences. METHOD: From April 1995 to September 2002, clinical and electrophysiologic features were reviewed for 18 patients with SMEI, who were diagnosed at epilepsy center, Inje University Sang-gye Paik Hospital. RESULTS: 1) Seizure onset age was 5.1+/-2.8 months (mean+/-SD) old. 2) Onset of febrile seizure was from 2 to 11 months of age (7.8+/-3.0 months) and febrile status epilepticus was also noted in 9 patients (50%). 3) Initial afebile seizure was noticed in 11 patients (61.1%). 4) Various types of seizures were manifested durign the patient's clinical courses 5) Myoclonic seizures were started from 7 to 48 months of age (26.5+/-12.1 months) and persisted in 14 (77.8%) patients. 6) Four patients (22.2%) had photosensitivity. 7) Mitochondrial cytopathy was suspected in 8 patients, and complex IV deficiency was confirmed in 1 patient. 8) Ketogenic diet was effective in 8 patients (61.5%) with seizure reduction more than 50% among 13 patients. 9) All sixteen patients who could be followed up for more than 12 months, showed normal initial development, and subsequently, all of them showed progressive delvelopmental delay with mild degree in 4 patients (22.2%), moderate degree in 7 patients (38.8%), and severe degree in 4 patients (22.2%). CONCLUSION: SMEI is one of the intractable childhood epileptic syndromes with variable clinical seizures and progressive developmental declining. SMEI should be paid more attention in epilepsy clinic for accurate diagnosis and adequate antiepileptic treatment including ketogenic diet.
Age of Onset ; Cytochrome-c Oxidase Deficiency ; Diagnosis ; Epilepsies, Myoclonic* ; Epilepsy ; Humans ; Ketogenic Diet ; Prognosis ; Seizures ; Seizures, Febrile ; Status Epilepticus

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

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.
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