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Metachromatic leukodystrophy (MLD) is a rare hereditary neurodegenerative disease caused by deficiency of the lysosomal enzyme arylsulfatase A (ARSA). This study described the clinical and molecular characteristics of 24 Chinese children with MLD and investigated functional characterization of five novel ARSA variants. A retrospective analysis was performed in 24 patients diagnosed with MLD at Guangzhou Women and Children's Medical Center in South China. Five novel mutations were further characterized by transient expression studies. We recruited 17 late-infantile, 3 early-juvenile, 4 late-juvenile MLD patients. In late-infantile patients, motor developmental delay and gait disturbance were the most frequent symptoms at onset. In juvenile patients, cognitive regression and gait disturbance were the most frequent chief complaints. Overall, 25 different ARSA mutations were identified with 5 novel mutations.The most frequent alleles were p.W320* and p.G449Rfs. The mutation p.W320*, p.Q155=, p.P91L, p.G156D, p.H208Mfs*46 and p.G449Rfs may link to late-infantile type. The novel missense mutations were predicted damaging in silico. The bioinformatic structural analysis of the novel missense mutations showed that these amino acid replacements would cause severe impairment of protein structure and function. In vitro functional analysis of the six mutants, showing a low ARSA enzyme activity, clearly demonstrated their pathogenic nature. The mutation p.D413N linked to R alleles. In western blotting analysis of the ARSA protein, the examined mutations retained reduced amounts of ARSA protein compared to the wild type. This study expands the spectrum of genotype of MLD. It helps to the future studies of genotype-phenotype correlations to estimate prognosis and develop new therapeutic approach. [ABSTRACT FROM AUTHOR]

Objective: To investigate and summarize the magnetic resonance imaging (MRI) manifestations of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children. Methods: We retrospectively analyzed data from 17 pediatric patients with autoimmune GFAP astrocytopathy confirmed by the detection of GFAP autoantibodies in cerebrospinal fluid in our single-center. Furthermore, we reviewed current literature and summarized previous findings on the MRI characteristics of this disease in children. Results: In these 17 patients, the clinical manifestations and results of CSF analysis were suggestive of autoimmune disorder, with a good improvement. The lesions on MRI were most commonly located in the bilateral basal ganglia (70.6%), thalamus (64.7%), cerebral white matter (29.4%). 93.3% of the cerebral lesions were relatively scattered and small, 80% of the spinal lesions presented as longitudinally extensive ones. Both periventricular radial linear (PVRL) (53.8%) and punctate or linear enhancement in basal ganglia and thalamus (53.8%) were commonly observed, followed by the leptomeningeal enhancement (46.2% in the brain and 62.5% in the spinal cord). We then included 55 pediatric patients with MRI data from current literature in our analysis (n = 72, 44 males). Our results revealed similar MRI findings but the enhancement pattern between our series and previously published cases, that is, leptomeningeal enhancement in the brain 46.2% vs 31.4%, in spinal cord 62.5% vs 18.4%, and PVRL enhancement 53.8% vs 11.2%. There were no detailed reports on punctate or linear enhancement. Conclusion: The MRI characteristics of autoimmune GFAP astrocytopathy in children could be suggestive. Scattered and small lesions (especially punctate or linear) in the bilateral thalamus, basal ganglia, and white matter, as well as longitudinally extensive spinal cord lesions (if present), with punctate, PVRL and leptomeningeal enhancement might be a distinct indication for the early diagnosis of this disorder. [ABSTRACT FROM AUTHOR]

Background: Studies suggested that myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are an isolated group of diseases that are different from multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). The proportion of individuals with MOGAD is higher among children. However, limited data are available on autoimmune antibodies and neuroimaging features in children with MOGAD. Methods: This study retrospectively reviewed 42 children with MOGAD. The clinical, neuroradiological, and cerebrospinal fluid data were compared according to courses and radiological results. Results: Of the 42 patients, 28 suffered a monophasic course and 14 had a relapsing course. During the follow-up magnetic resonance imaging (MRI), 21 patients had a well-resolved brain condition and another 21 patients showed slight improvement with marked residuals. Most patients with relapse had cortical lesions and a leukodystrophy-like MRI pattern (all p < 0.05). Children with poor radiological outcomes have confluent and hazy lesions that involve both cortexes, white matter lesion of > 2 cm, and a leukodystrophy-like pattern, as well as cerebral lesions with T1 hypointensity or enhancement and spinal lesions (all p < 0.05). The multivariable logistic regression analysis used the aforementioned differential features and showed cerebral enhancement and a leukodystrophy-like pattern as the most effective variations associated with poor radiological outcomes of MOGAD with an area under the curve of 0.875. Conclusion: MOGAD in children have some radiological features suggestive of clinical courses and radiological outcomes. A good understanding of these differential features can help to give early warnings of disease recurrence or poor radiological improvement and develop subsequent therapeutic strategies. [ABSTRACT FROM AUTHOR]

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Early-onset ataxia, hearing loss, hypomyelinating, cerebellar atrophy and thin corpus callosum are consistent in our case, which confirms that I RNF220 i is a novel gene related to this combination of phenotypes. A recent study in I Brain i [1] identified two homozygous missense variants in I RNF220 i [p.(R363Q) and p.(R365Q)] in five European pedigrees with ataxia, deafness, hypomyelinating leukodystrophy, liver dysfunction and dilated cardiomyopathy. [Extracted from the article]

Adult-onset autosomal dominant leukodystrophy (ADLD) is a lately described rare form of leukodystrophy with only one family report from China. As the only disease associated with increased lamina B1 encoded by LMNB1 , ADLDs have different clinical presentations, ranging from autonomic to pyramidal tract and cerebellar ataxia. Here, we report a case of ADLD that presented with positional tremor as the initial symptom. T2-weighted brain MRI showed brain atrophy and diffuse high signal intensity of the cerebral white matter and the brain stem. The precise diagnosis was made by identification of the mutated gene. To the best of our knowledge, this is perhaps the first case report of ADLD presenting as tremor in China. [ABSTRACT FROM AUTHOR]