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Background: LMNA-related muscular dystrophy can manifest in a wide variety of disorders, including Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy (LGMD), and LMNA-associated congenital muscular dystrophy (L-CMD). Muscle magnetic resonance imaging (MRI) has become a useful tool in the diagnostic workup of patients with muscle dystrophies. This study aimed to investigate whether there is a consistent pattern of MRI changes in patients with LMNA mutations in various muscle subtypes. Methods: Twenty-two patients with LMNA-related muscular dystrophies were enrolled in this study. MRI of the thigh and/or calf muscles was performed in them. The muscle MRI features of the three subtypes were compared by the Mann-Whitney U-test. The relationship between the clinical and MRI findings was also investigated by Spearman's rank analyses. Results: The present study included five EDMD, nine LGMD, and eight L-CMD patients. The thigh muscle MRI revealed that the fatty infiltration of the adductor magnus, semimembranosus, long and short heads of the biceps femoris, and vasti muscles, with relative sparing of the rectus femoris, was the predominant change observed in the EDMD, LGMD, and advanced-stage L-CMD phenotypes, although the involvement of the vasti muscles was not prominent in the early stage of L-CMD. At the level of the calf, six patients (one EDMD, four LGMD, and one L-CMD) also showed a similar pattern, in which the soleus and the medial and lateral gastrocnemius muscles were most frequently observed to have fatty infiltration. The fatty infiltration severity demonstrated higher scores associated with disease progression, with a corresponding rate of 1.483 + 0.075 × disease duration (X) (r = 0.444, P = 0.026). It was noteworthy that in six L-CMD patients with massive inflammatory cell infiltration in muscle pathology, no remarkable edema-like signals were observed in muscle MRI. Conclusions: EDMD, LGMD and advanced-staged L-CMD subtypes showed similar pattern of muscle MRI changes, while early-staged L-CMD showed somewhat different changes. Muscle MRI of L-CMD with a muscular dystrophy pattern in MRI provided important clues for differentiating it from childhood inflammatory myopathy. The fatty infiltration score could be used as a reliable biomarker for outcome measure of disease progression.

Objective: To identify the magnetic resonance (MR) features of a group of pediatric patients with Leigh syndrome (LS) caused by SURF1 gene 604G→C mutation. Materials and Methods: Eight cases with definite diagnosis of SURF1 gene 604G→C mutation in our hospital were reviewed. Most cases presented typical symptoms in their infancy or childhood, with psychomotor regression, hypotonia, or eye movement disturbances. They all underwent cranial MR examinations after the onset. Their brain images were reviewed by an experienced neuroradiologist to determine the abnormalities. Results: The data of our group showed heterogeneous neuroradiological findings: involvement of the brain stem and subthalamic nuclei was found in only three cases; basal ganglia abnormalities were detected in two cases, whereas demyelination was demonstrated in four cases; and brain atrophy existed invariably in the group. Conclusion: The MR presentation in LS patients with SURF1 gene 604G→C mutation is variable. Maybe it is not appropriate to correlate a specific gene mutation with a homogenous radiological pattern.

To delineate the phenotype and genotype characteristics in 12 Chinese children with Alexander disease (AD), which is helpful for the molecular diagnosis and genetic counseling in China.Clinical diagnosis of AD was based on MRI criteria proposed by van der Knaarp in 2001. Included AD patients were followed up for 0.50 - 3.67 years. Mutations in GFAP were detected by DNA sequencing.The 12 cases of AD were clinically diagnosed. Age of first visit was 4.87 years (0.75 - 12.00 years), with 3 types of chief complaints: developmental delay in 3, recurrent seizures in 7, unable to walk after falling in 2. Average head circumference was 52.34 cm (44 - 58 cm), which larger than age-matched average by 6.45% (1.80% - 13.95%). On the first visit, scaling according to Gross motor functional classification system (GMFCS) was performed, with GMFCSI in 8, II in 3, V in 1. Mild to severe cognitive dysfunction were found in 8, and seizures in 11 cases. The 12 patients were followed up for 0.50 - 3.67 years, their motor and cognitive function remained stable. Episodic aggravations provoked by fever or falling were observed in 5 cases (41.67%). Heterozygous missense mutations of GFAP were detected in 12 patients. All mutations were de novo; 3 out of 10 mutations identified were novel. R79 and R239 were hot mutations, which was consistent with previous reports. Mutations were located in exon 1 in 8 cases.The phenotype in these patients is characterized by slower progression compared with reports from other population and high incidence of seizures. And episodic aggravations provoked by fever or falling were more common. The genotype characteristics are consistent with previous reports. The results of this research expanded the number of patients with Alexander disease found to have GFAP coding mutations in China.

To study the clinical and enzymological characteristics of the children with mitochondrial respiratory chain complex III deficiency.The clinical manifestations of five patients (3 males, 2 females) were summarized. Spectrophotometric assay was used for the analysis of respiratory chain complex I to V enzyme activity in peripheral blood leukocytes, after obtaining venous blood.(1) Five patients were hospitalized at the age of 1 month to 15 years. Three patients had Leigh syndrome with progressive motor developmental delay or regression and weakness. One had severe liver damage and intrahepatic cholestasis. One presented muscle weakness. (2) Deficient complex I + III activity was identified in five patients. Their complex I + III activities in peripheral blood leukocytes were 3.0 to 14.2 nmol/min per mg mitochondrial protein (control: 84.4 ± 28.5 nmol/min per mg mitochondrial protein). The ratio of complex I + III to citrate synthase decreased to 3.5 to 22.9% (normal control 66.1 ± 14.7%). The activities of complex III decreased to 10.4 to 49.3% of the lowest control value, while complex I, II, IV and V activities were normal. The results supported the diagnosis of isolated respiratory chain complex III deficiency.Complex III deficiency is a kind of disorder of energy metabolism with various manifestations. The complex I + III activities and the ratio of complex I + III to citrate synthase were lower than those of the control. The activities of complex I, II, IV and V were normal.

3-Hydroxy-3-methylglutaric aciduria is a rare disorder of organic acid metabolism caused by 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. The disorder was common in neonatal or infant period. Here a case of late onset 3-hydroxy-3-methylglutaric aciduria complicated by leucodystrophy was reported. The patient was a 7-year-old boy. He presented with progressive headache, drowsiness and vomiting. Hepatic lesions, ketosis and leucopenia were found. Symmetrical diffused leucodystrophy was shown by MRI. Blood levels of isovalerylcarnitine and acetylcarnitine increased significantly. Urinary levels of 3-hydroxy-3-methylglutaric, 3-methylglutaconic, 3-hydroxyglutaric acids and 3-methyl-crotonylglycine increased significantly. Symptoms were released by intravenous infusion of L-carnitine and glucose. After treatment for 6 months, urinary levels of 3-hydroxy-3-methylglutaric aciduria decreased in the boy and his health improved.

To analyze and review the characteristics of leukoencephalopathy with vanishing white matter (VWM).The clinical features including clinical manifestations, neurologic signs, cranial MRI and laboratory tests in 9 patients with the diagnosis of VWM were analyzed and the characteristics of the disease were reviewed.8 cases had symptoms involving central nervous system, 1 case only showed abnormal cranial MRI findings. The onset of the disease occurred between 6 months to 3 years of age. Family history was positive in 5 cases. Almost all cases had normal psychomotor development before the onset of the disease. The initial symptom was usually movement disorder with predominant involvement of lower limbs. The onset or deterioration of the disease was followed by respiratory tract infection in 6 cases and minor head trauma preexisted in 3 cases. The course of the disease was progressive in 7 cases and there was episodic deterioration in 4 cases. Mental abilities were relatively better preserved. Head circumference was normal in 7 cases. Positive upper motor unit signs were found in 8 cases and ataxia in 4 cases. Bilateral optic nerve atrophy was found in 3 cases. Cranial MRI indicated diffuse and symmetrical involvement of deep white matter which showed long T(1) and T(2) signal. Subcortical white matter was also involved with predominance in frontal and parietal lobes. Flair image showed symmetrical high signal intensity in cerebral white matter with low signal intensity similar to that of CSF in partial area or low signal in most area of white matter with only meshwork of higher signal preserved. The results of all the laboratory tests including the enzyme and biochemical test specific for some well-known leukoencephalopathy were normal.The clinical features of VWM include: 1. Initial symptom is usually movement disorder; 2. Movement disorder is more prominent compared to mental retardation; 3. Cranial MRI shows symmetrical abnormal T(1) and T(2) signal in deep white matter with signs of vanishing white matter. Exclusion of other hereditary and acquired leukoencephalopathy is necessary for diagnosis. Final diagnosis should be made on the basis of genetic evidence.

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.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.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.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.

X-linked adrenoleukodystrophy (ALD) is a genetically determined disorder that involves the nervous system white matter, axons, adrenal cortex and testes. The typical clinical manifestations are progressive psychomotor regression, vision and/or auditory impairment and adrenal insufficiency. The clinical manifestation, biochemical change and genetic counseling work of X-linked ALD were analyzed.The clinical features of 29 cases with ALD were summarized and analyzed, including symptoms and signs, measurement of blood very long chain fatty acids (VLCFA), adrenal function, cranial magnetic resonance imaging (MRI) and pedigree investigation.Among these 29 cases, the clinical phenotype could be classified into childhood cerebral (22 cases), adolescent cerebral (4 cases), adrenomyeloneuropathic (1 case), Addison's disease (1 case) and asymptomatic or presymptomatic (1 case) types. Nine of them had positive family history. Pedigree investigation was consistent with typical sex-linked recessive inheritance. There were 45 ALD patients in these 29 pedigrees. The neurological manifestations varied among members of the same family. Nine cases died during follow up. The causes of death were central respiratory failure or other complications of ALD and so on. Laboratory tests demonstrated abnormally high plasma levels of VLCFA in ALD patients; MRI demonstrated symmetric butterfly-like low T(1) and high T(2) signals in the parieto-occipital white matter. The impairment in the splenium of corpus callosum made the bilateral lesion region converge into one. It could progress anteriorly and injure the bilateral posterior limb of internal capsule and the temporal lobe, and could injure the brainstem inferiorly. Following intravenous injection of contrast material, thin stripe of lacelike enhancement could be observed.The atypical initial symptom of ALD was seizures. The MRI showed abnormal signal in the cerebellar white matter. This disease can influence the normal development of children, this was more pronounced in the childhood cerebral ALD type. It tended to progress rapidly with dementia, vegetative state or death. Since antenatal diagnostic method is available now, emphasis should be made on the antenatal examination in order to make an early diagnosis and abort pregnancy if necessary.