Case report of neurodevelopmental disorder associated with de novo MORC2 mutation / 中华实用儿科临床杂志

The clinical data of a child with MORC2 gene mutation related neurodevelopmental disorder treated in Fujian Medical University Union Hospital in July 2020 were analyzed retrospectively.The male (7-year-old)patient was global retardation from infant, with special face, short stature, small head circumference, decreased muscle strength and positive pyramidal tract sign of lower limbs.Brain magnetic resonance imaging was similar to the changes of Leigh syndrome.Genetic testing found de novo mutation in MORC2 gene chr22: 31345763, c.292G>A(p.Gly98Arg). And literature review found that there was only one related report. MORC2 gene mutation related neurodevelopmental disorder is a newly discovered syndrome, and c. 79G>A(p.Glu27Lys) is the most common mutation.This case enriched the clinical phenotype and genotype of neurodevelopmental disorder related to MORC2 gene.

Mitochondrial encephalopathy, lactic acidosis and stroke-like episodes / myoclonus epilepsy with ragged-red fibers /Leigh overlap syndrome caused by mitochondrial DNA 8344A>G mutation / 北京大学学报(医学版)

OBJECTIVE@#Mitochondrial deoxyribonucleic acid (mtDNA) 8344 A>G (m.8344A>G) mutation is the common mutation associated with mitochondrial myoclonus epilepsy with ragged-red fibers (MERRF) syndrome. Herein we report a rare case with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes/MERRF/Leigh (MELAS/MERRF/Leigh) overlap syndrome caused by m.8344A>G mutation.@*METHODS@#The clinical and imaging data of the patient were collected and an open muscle biopsy was carried out. We further employed molecular genetic analyses to detect mtDNA mutation in the proband and his mother. And then a clinical and neuroimaging follow-up was performed.@*RESULTS@#This patient was a 25-year-old male, who developed exercise intolerance since the age of 6. At age 10, he suffered from acute episodes of hemianopia, and cranial magnetic resonance imaging (MRI) showed occipital stroke-like lesions and cranial magnetic resonance spectroscopy (MRS) revealed a lactate peak corresponding to the lesion. After that the patient presented slowly progressive psychomotor decline. He had myoclonic seizures and cerebellar ataxia since the age of 12. At age 21, he was admitted to our hospital because of confusion and cranial MRI revealed symmetrical lesions in bilateral posterior putamen, thalami and midbrain. Then repeated MRI showed progression of original lesions and new frontal multiple stroke-like lesions. Symptomatic and rehabilitation treatment relieved his condition. Follow-up cranial MRI at age 24 showed the lesions in basal ganglia and thalami diminished, and the midbrain lesions even completely vanished. Muscle pathology indicated the presence of numerous scattered ragged-red fibers (RRF), suggestive of a mitochondrial disorder. Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) detected the m.8344A>G mutation of the MT-TK gene encoding mitochondrial transfer RNA for lysine in the patient's blood. Next generation sequencing (NGS) of the whole mitochondrial genome identified that the proportion of m.8344A>G was 90%, and no other mtDNA mutation was detected. Sanger sequencing further identified this mutation both in the proband and his mother's blood, although the mutation load was much lower in his mother's blood with approximately 10% heteroplasmy.@*CONCLUSION@#The present study is the first to describe a patient with m.8344A>G mutation in association with the MELAS/MERRF/Leigh overlap syndrome, which expands the phenotypic spectrum of the m.8344A>G mutation.

Leigh syndrome (French Canadian type) caused by compound heterozygous mutations of LRPPRC gene: a case report / 中华神经科杂志

Leigh syndrome (French-Canadian type, LSFC) is a rare autosomal recessive hereditary severe neurological disorder that begins in infancy. Herein we report a case with LSFC in China. The patient was 8 months old, male, whose clinical manifestations included delayed development, low muscle tone, unstable vertical head, inability to sit alone, cognitive impairment, slightly smaller forehead, oblique eyes, epilepsy, etc. Gene sequencing results showed that the LRPPRC gene in the infant had complex heterozygous mutations of c.2989G>A (newly reported) and c.4078G>A. Combined with the clinical manifestations, gene mutations and literatures, the infant was diagnosed as LSFC, and symptomatic rehabilitation was performed. The results of genetic testing can contribute to the early diagnosis and genetic counseling of LSFC patients, and help reduce the burden on the patients and their families.

Leigh Syndrome Due to mtDNA Pathogenic Variants

Abstract Leigh syndrome is a devastating neurodegenerative disease, typically manifesting in infancy or early childhood. Hallmarks of the disease are symmetrical lesions in the basal ganglia or brain stem on MRI, and a clinical course with rapid deterioration of cognitive and motor functions. It is genetically heterogeneous, causative mutations have been disclosed in mitochondrial DNA and nuclear genes involved in the process of energy production in the mitochondria .We investigated the whole mitochondrial DNA in three Brazilian patients with LS, based on their clinical and biochemical data, with the aim to identify the disease-causing mutations. In two of the patients, with complex I deficiency, a novel heteroplasmic variant m.4142G>T (p.R279L) in MT-ND1 and a recurrent homoplasmic mutation m.10197G>A (p.A47T) in MT-ND3 were identified. In the remaining patient, with complex IV deficiency, a de novo heteroplasmic variant in MT-CO1 m.6547T>C (p.L215P) was found. The molecular investigation in mitochondrial diseases have shifted their focus from mitochondrial DNA to nuclear DNA, however, mtDNA protein-coding genes are one of the important genetic causes of mitochondrial disorders for Leigh syndrome. This study expands the molecular and clinical spectrum associated with this disease.

Síndrome de leigh: a propósito de um caso clínico com mutação no dna mitocondrial / Leigh syndrome: a case report with a mitochondrial dna mutation

RESUMO Objetivo: A síndrome de Leigh é uma doença neurodegenerativa com incidência de 1:40.000 nados-vivos. Apresenta ampla heterogeneidade clínica, bioquímica e genética, mas com alterações neuropatorradiológicas homogêneas. Não existe tratamento específico, e o prognóstico é reservado. O objetivo deste estudo foi familiarizar os profissionais de saúde com a doença. Descrição do caso: Menina de 16 meses, com hipotonia axial e atraso do desenvolvimento psicomotor. Dos exames realizados: cariótipo, potenciais auditivos evocados e avaliação oftalmológica normais; presença de hiperlactacidemia e hipocitrulinemia. Após a realização de ressonância magnética cerebral sob anestesia, observou-se agravamento da hipotonia com necessidade de internação por episódios de cianose/apneia. O eletroencefalograma não mostrou atividade epileptiforme. A neuroimagem revelou hipersinal lenticular bilateral com lesão do putâmen e do globo pálido esquerdo. Encontrou-se a mutação 8993T>G (MT-ATP6) no DNA mitocondrial. Comentários: De 10 a 30% dos doentes com síndrome de Leigh apresentam mutações do DNA mitocondrial. A descompensação com agravamento neurológico após intervenção anestésica está descrita e, nesse caso, apoiou o diagnóstico. Importante alertar para casos semelhantes, com diminuição de exames invasivos para diagnóstico.

ABSTRACT Objective: Leigh syndrome is a neurodegenerative disorder with an incidence of 1:40,000 live births. It presents wide clinical, biochemical, and genetic heterogeneity, but with homogenous neuropatoradiological alterations. There is no specific treatment, and the prognosis is reserved. This case report aimed familiarize health professionals with the disease. Case Description: A 16-month-hold girl who was followed in outpatient clinic due to axial hypotonia and delayed psychomotor development. Karyotype, auditory evoked potentials and ophthalmologic evaluation were normal. Evidence of hyperlactacidemia and hypocitrullinemia was detected in the patient. After performing brain magnetic resonance under anesthesia, hypotonia got worse, and the patient was hospitalized after an episode of cyanosis and apnea. The electroencephalogram showed no epileptiform activity. Neuroimaging revealed bilateral lenticular hyperintensity, especially in the putamen and in the left globus pallidus regions. Molecular analysis revealed an 8993T>G (MT-ATP6) mutation in the mitochondrial DNA. Comments: Between 10 and 30% of individuals with Leigh syndrome have mitochondrial DNA mutations. The decompensation after anesthetic intercurrences is typically associated with neurological deterioration and, in this case, increased the diagnosis suspicion. It is important to alert for similar cases and to reduce invasive diagnostic tests if the diagnosis is suspected.

Diagnóstico clínico y bioquímico del síndrome de leigh en cinco pacientes colombianos / Clinical and biochemical diagnosis of leigh syndrome in five colombian patients / Diagnóstico clínico e bioquímico da síndrome de leigh em cinco pacientes colombianos

Resumen El síndrome de Leigh (SL) es una enfermedad neurodegenerativa, descrita como una encefalomielopatía necrotizante subaguda, y es una de las enfermedades de origen mitocondrial más frecuentes. El SL es causado por el déficit en la producción de energía, originada en defectos en los genes que codifican alguno de los complejos mitocondriales; el gen afectado puede ser de codificación tanto nuclear como mitocondrial, lo que explica que se encuentren diferentes mecanismos de herencia, incluyendo autosómica recesiva y herencia materna, lo que, a su vez, hace más difícil su diagnóstico molecular. Clínicamente se presenta con regresión del desarrollo cognitivo y pérdida de habilidades motoras con trastorno de movimiento, de rápida progresión. El diagnóstico se basa en la demostración bioquímica de la elevación del ácido láctico y de la relación lactato/piruvato, así como hallazgos en las neuroimágenes por resonancia magnética que muestran lesiones focales, bilaterales y simétricas en ganglios basales o tallo cerebral asociadas a leucoencefalopatía y atrofia cerebral. Se reportan cinco casos con diagnóstico clínico y bioquímico del SL que ejemplifican la variabilidad clínica y gravedad encontrada en este grupo de pacientes.

Summary Leigh syndrome (LS) is a neurodegenerative disease, described as a subacute necrotizing encephalomyelopathy and is one of the most frequent diseases of mitochondrial origin. LS is caused by a deficit in the energy production due to defects in the genes that encode some of the mitochondrial complexes. The affected gene can be due to either nuclear and/or mitochondrial coding, which explains why there are different ways of inheriting the disease, including autosomal recessive and maternal inheritance, which makes its molecular diagnosis even more difficult. Clinically, LS is characterized by regression in cognitive development and motor abilities, as well as movement disorders of rapid progression. Its diagnosis is based on the biochemical demonstration of an increase in lactic acid and lactate / pyruvate ratio, as well as magnetic resonance neuroimaging findings showing focal, bilateral and symmetric lesions in basal ganglia or brainstem associated with leukoencephalopathy and cerebral atrophy. Five cases are reported with clinical and biochemical diagnosis of LS that exemplify the clinical variability and severity found in this group of patients.

Resumo A síndrome de Leigh (SL) é uma doença neurodegenerativa, descrita como uma encefalomielopatia necrotizante subaguda e é uma das doenças de origem mitocondrial mais frequente. A SL é causada pelo déficit na produção de energia originada em defeitos nos genes que codificam algum dos complexos mitocondriais; o gene afetado pode ser de codificação tanto nuclear como mitocondrial, o que explica que se encontrem diferentes mecanismos de herança, incluindo autossômica recessiva e herança materna, o que torna mais difícil seu diagnóstico molecular. Clinicamente se apresenta com regressão do desenvolvimento do desenvolvimento cognitivo e perda de habilidades motoras com transtorno de movimento, de rápida progressão. O diagnóstico se baseia na demonstração bioquímica da elevação do ácido láctico e da relação lactato/piruvato, assim como descobertas nas neuro imagens por ressonância magnética que mostram lesões focais, bilaterais e simétricas em gânglios basais ou talo cerebral associadas a leucoencefalopatia e atrofia cerebral. Reportam-se cinco casos com diagnóstico clínico e bioquímico da SL que exemplificam a variabilidade clínica e gravidade encontrada neste grupo de pacientes.

Clinical, Neuroimaging, and Pathological Analyses of 13 Chinese Leigh Syndrome Patients with Mitochondrial DNA Mutations / 中华医学杂志(英文版)

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.

Leigh Syndrome: Subgroup Aanalysis according to Mitochondrial DNA Mutation / 대한소아신경학회지

PURPOSE: Leigh syndrome (LS) is a rare, progressive neurodegenerative disorder with characteristic abnormalities in the central nervous system. Such patients present with heterogeneous clinical symptoms and genetic abnormalities; thus, prognosis is difficult to anticipate. The present study investigates whether distinct patient characteristics are associated with mitochondrial DNA (mtDNA) mutation in LS patients. METHODS: We retrospectively analyzed data from patients diagnosed with LS at our hospital who were assessed using genomic sequencing of mtDNA. A subgroup analysis was performed to divide patients according to the mtDNA sequencing results. RESULTS: Among the 85 patients enrolled, 18 had mtDNA mutations. Most patients had lactic acidosis and a lactate/pyruvate ratio above 20, indicating respiratory chain abnormalities. In the subgroup analysis, the mutation group had a significantly higher female-to-male ratio, alanine level, ocular involvement, and midbrain and medulla abnormalities on magnetic resonance imaging (MRI). CONCLUSION: The subgroup analysis indicates that mtDNA sequencing is recommended for female patients, or those who exhibit ocular involvement, high alanine levels, or MRI findings with lesions in the midbrain and medulla.

Clinical analysis of 4 cases of Leigh syndrome in children / 临床儿科杂志

Objective To explore the clinical manifestation, diagnosis and prognosis of Leigh syndrome in children. Method Clinical data from 4 cases of Leigh syndrome conifrmed by genetic testing were retrospectively analyzed. The related literature were reviewed. Results In 4 cases, 3 were boys and one was a girl, 3 cases were onset in infant and one case was in school age. The main manifestations were mental retardation, low muscle tone, convulsions, feeding dififculties, drooping eyelids, extraocular muscle paralysis and nystagmus, irritation, activity intolerance etc. The brain magnetic resonance imaging (MRI) revealed symmetry long T1, T2 abnormal signal in brainstem, bilateral globus pallidus, thalamus, cerebellar dentate nuclei, and periaqueductal, 3 cases involved midbrain, one case involved thalamus, and one case involved cerebellar dentate nuclei;2 cases had encephalatrophy. Electromyography was normal in all cases. The levels of lactate in blood and cerebrospinal lfuid were increased. Mitochondrial DNA (mtDNA) detection found the mutation of mtDNA 8993 T>G in one case, and the mutation of mtDNA 9176 T>C in another 3 cases. The case onset in school age died of respiratory failure one month later, and another 3 cases were still in follow up, there were mental retardation, but no signiifcant setback. Conclusion The clinical manifestations of Leigh syndrome in children are diverse. The diagnosis is based on the typical clinical manifestations and MRI, blood and/or cerebrospinal lfuid lactate levels. The genetic testing is the golden standard for diagnosis.

Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome

BACKGROUND AND PURPOSE: Few studies have analyzed the clinical course and functional outcome in Leigh syndrome (LS). The aim of this study was to determine the clinical, radiological, biochemical, and genetic features of patients with LS, and identify prognostic indicators of the disease progression and neurological outcome. METHODS: Thirty-nine patients who had been diagnosed with LS at the Seoul National University Children's Hospital were included. Their medical records, neuroimaging findings, and histological/biochemical findings of skeletal muscle specimens were reviewed. Targeted sequencing of mitochondrial DNA was performed based on mitochondrial respiratory chain (MRC) enzyme defects. RESULTS: Isolated complex I deficiency was the most frequently observed MRC defect (in 42% of 38 investigated patients). Mitochondrial DNA mutations were identified in 11 patients, of which 81.8% were MT-ND genes. The clinical outcome varied widely, from independent daily activity to severe disability. Poor functional outcomes and neurological deterioration were significantly associated with early onset (before an age of 1 year) and the presence of other lesions additional to basal ganglia involvement in the initial neuroimaging. CONCLUSIONS: The neurological severity and outcome of LS may vary widely and be better than those predicted based on previous studies. We suggest that age at onset and initial neuroimaging findings are prognostic indicators in LS.

Subacute necrotizing encephalomyelopathy (Leigh syndrome) in pediatric patients: a retrospective study.

Background: The clinical manifestations of Leigh Syndrome (LS) are heterogeneous and its diagnosis is often based on information acquired from multiple levels of inquiry. To identify LS, Oral Glucose Lactate Stimulation Test (OGLST) and Magnetic Resonance Spectroscopy (MRS) have been used as additional tools for evaluation of this metabolic disorder. The objective of the study was to report the clinical manifestations, neuroimaging assessments, and multidisciplinary approaches of lactate in pediatric patients with LS. Methods: We performed a retrospective charts review of pediatric patients with LS, which underwent the investigations using laboratory tests and Magnetic Resonance Images (MRI)/MRS of the brain. Results: The distributions of the lesions on the MRI of the brain studies were as the following: basal ganglia (7/8), brainstem (7/8), and cortex (3/8). Despite all of the patients showed disorient neurological manifestations and symmetrical lesions over the basal ganglion and brainstem on MRI, elevated levels of serum lactate were detected in 6 of 8 patients by either random serum sample obtained for lactate or OGLST. Subsequently, the remaining 2 cases were demonstrated with lactate peak over the affected areas by MRS. Cranial MRS showed lactate duplex and decreased N-acetylaspartate/creatine ratio over the affected areas in the 5 of 6 patients. Conclusions: The study shows the importance of multidisciplinary approaches in the diagnosis of LS. Approach of LS may not only depend on the elevation of the value of random serum lactate but also can be further aided by OGLST or MRS to evaluate metabolic disorder in such patients.

Ocular manifestations in Leigh syndrome / 소아과

PURPOSE: Leigh syndrome is a typical type of mitochondrial disease. This study was conducted to analyze the types of ophthalmologic symptoms and results of funduscopy conducted in the ophthalmologic examination of patients with Leigh syndrome. METHODS: Funduscopy was conducted on 24 subjects, who were chosen among those diagnosed as having mitochondrial respiratory chain complex defect and who were clinically suitable for the criteria of Leigh syndrome. Their clinical features, ophthalmologic symptoms, and ophthalmologic examination results were retrospectively analyzed. RESULTS: Of the 24 patients with Leigh syndrome, 11 developed ophthalmologic symptoms and no abnormal finding was observed in 13. The most frequent abnormal finding was visual disturbance in 5 patients. Funduscopy revealed abnormal findings in 17 patients; retinal pigmentation was the most frequent abnormality and was seen in 9 patients. CONCLUSION: Funduscopy can be an important screening test to find ophthalmologic abnormalities among patients with mitochondrial disease (MD), including those patients whose ophthalmologic symptoms are inconspicuous. It is predicted that an improved screening test can be made in the future that will identify risk factors related to ophthalmologic symptoms.

Leigh syndrome: MRI findings in two children

Leigh syndrome is a progressive neurodegenerative disorder of childhood. The symmetrical necrotic lesions in the basal ganglia and/or brainstem which appear as hyperintense lesions on T2-weighted MRI is characteristic and one of the essential diagnostic criteria. Recognising this MR imaging pattern in a child with neurological problems should prompt the clinician to investigate for Leigh syndrome. We present here two cases of Leigh syndrome due to different biochemical/genetic defects, and discuss the subtle differences in their MR neuroimaging features.

Leigh Syndrome : Two cases report

Leigh syndrome is a subacute necrotizing encephalomyelopathy of infancy or early childhood. The clinical presentation can be highly variable. The classical presentations are central hypotonia, developmental regression or arrest, ataxia, ophthalmoplegia, and abnormal respiratory pattern. Diagnosis is usually confirmed by radiologic evidence of focal, bilateral and usually symmetric lesions of the both gray and white matter in the brain and the spinal cord. We experienced 2 cases of Leigh syndrome in a brother and sister.The first case, 4 year-old boy, was misdiagnosed as a cerebral palsy initially, but after acute infection, he revealed developmental regression and abnormal movement. His disease was confirmed by typical magnetic resonance imaging findings. The second case, 1 year-old girl with nystagmus, showed bilateral symmetric high signal intensity in globus pallidus on T2WI. We reported these cases with a brief review of the related literature.

A Case of Leigh Syndrome with Typical MRI and MRS Findings

Leigh syndrome (LS) is a genetically and clinically heterogeneous disorder caused by metabolic defects affecting lactate/pyruvate metabolism. The consequence of the metabolic defects are decreased amounts of APT and basic cell energy productions of the nervous system. In LS, several mutations have been reported in both the nuclear and the mitochondrial genome. Here, we report a 26-year-old woman clinically diagnosed with LS having characteristic brain MR and MRS abnormalities but without known definite pathogenetic mitochondrial DNA mutations.

Leigh Syndrome: Clinical, Radiological, and Mitochondrial Mutational Study

PURPOSE: Leigh syndrome is a subacute neurodegenerative disorder of infancy or early childhood characterized by variable clinical manifestations and characteristic pathologic findings on brain. The characteristic radiological findings revealed bilateral symmetrical high signal intensity in T2-weighted brain MRI imaging. The previous studies reported defects of enzymes involved in aerobic energy metabolism or point mutations in mitochondrial deoxyribonucleic acid(mtDNA), including a T-to-C or T-to-G mutation at nucleotide position(nt) 8993 or 9176 located in adenosinetriphosphatase(ATPase) 6 gene of mtDNA. Therefore, we studied the characteristic clinical, radiological, and genetical findings of Leigh syndrome, diagnosed at the Department of Pediatrics, Asan Medical Center. METHODS: From August 1992 to June 2000, 17 patients were included in this study, who presented charateristic MRI findings of Leigh syndrome. We examined the concentrations of lactate and pyruvate in blood and cerebrospinal fluid(CSF), and obtained MRS from 12 patients. For mutational analysis, fibroblasts from skin biopy were obtained from 17 patients. We analyzed the T8993C or T9176C mutation at ATPase 6 gene. RESULTS: The male to female ratio is 12 to 5, and the age of onset is from 2 month to 8 year. Among the total 17 patients, 4 patients died, 4 patients alive yet, and 9 patients were unable to be followed up. The clinical manifestations were developmental delay or retardation(n=11, 64.7%), respiratory difficulty(n=10, 58.8%), altered consciousness (n=7, 41.2%), strabismus or ophthalmoplegia(n=5, 29.4%), feeding difficulty(n=5, 29.4%), etc. T2-weighted brain MRI showed bilateral high signal intensity in basal ganglia, brainstem, thalamus, periaqueductal gray matter, cerebral peduncle, substantia nigra, cerebellum, subcortical white matter. MRS was performed on 12 patients and showed lactate peak increase in ten patients(83.3%) and N-acetylaspartate peak decrease in two patients (16.7%). The concentrations of lactate and pyruvate in CSF and blood were obtained, and lactate/pyruvate ratio was calculated. We observed the elevation of ratio in 3(33.3%) of 9 cases in CSF, 7(63.6%) of 11 cases in blood, respectively. Our mutation analysis revealed that T8993C mutation in one patient and T9176C mutation in another patient were confirmed among the total 17 patients. CONCLUSION: Our study confirmed a case of the T8993C and a case of the T9176C mutation among 17 patients of Leigh syndrome. Therefore, Leigh syndrome is a genetically heterogenous disorder and further genetic study will be needed.

Serial MRI Findings in a Clinically Diagnosed Adult Onset Leigh Syndrome

Adult onset Leigh syndrome is a very rare neurodegenerative disorder of unknown cause. We report the evolution of the lesions on serial MRIs in a 38-year-old man with clinically diagnosed Leigh syndrome. We emphasize that the mammillary bodies can be involved during the disease course and that premortem diagnosis of Leigh syndrome is pos-sible, if a characteristic distribution of lesions can be demonstrated on MRI.