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Abstract Background Bainbridge–Ropers syndrome (BRPS) is a recently described developmental disorder caused by de novo truncating mutations in the Additional sex combs-like 3 (ASXL3) gene. Only four cases have been reported in China and are limited to the analysis of its clinical abnormalities, medical imaging features and gene variation. The aim of this study was to investigate the clinical phenotype, imaging manifestations and genetic characteristics of BPRS syndrome caused by ASXL3 gene mutation. Clinical data, medical imaging data and gene test results of BRPS in infant patients were retrospectively analyzed, and related literature was summarized. Case presentation At the age of 8 months, brain MRI showed that the subarachnoid space of the forehead was widened, part of the sulci was deepened, and the corpus callosum was thin. The development quotient (DQ) was determined using the 0~6-year-old pediatric examination table of neuropsychological development at 6 months and 8 months. The DQ of both tests was less than 69. Whole-exome sequencing revealed a heterozygous frameshift mutation c.3493_3494deTG in exon 12 of the ASXL3 gene, resulting in the amino acid change p. (Cys1165Ter). No variation was present at this site in her parents. Sanger sequencing of family members validated this analysis, suggesting a de novo mutation. The de novo ASXL3 mutations generated stop codons and were predicted, in silico, to generate a truncated ASXL3. Conclusions The main clinical features of the patient included psychomotor development retardation, difficulty in feeding, hypotonia, and special facial features. MRI features showed that brain development lagged behind that of normal children. Genetic testing is helpful in the early diagnosis of BRPS.

Background: The mut methylmalonic acidemia (MMA) caused by the deficiency of methylmalonyl-CoA mutase (MCM) activity, which results from defects in the MUT gene. The aim of this study was to summarize the clinical and biochemical data, spectrum of mutations, treatment regime and follow-up of patients with mut MMA from Jan 2013 to Dec 2017 in Shandong province, China. Methods: Twenty patients were diagnosed with isolated mut MMA by elevated C3, C3/C2, and urine methylmalonic acid levels without hyperhomocysteinemia. The MUT gene was amplified and sequenced. Most patients received treatment with specific medical nutrition and oral l-carnitine after diagnosis. Metabolic parameters, clinical presentation and mental development were followed up. Results: Among 20 patients with mut MMA, 14 had clinical presentations, and 12 presented in the neonatal period. Three patients died of metabolic crises triggered by infection. Twenty-three different mutations were detected, and four mutations (c.613G > A, c.446A > G, c.920-923delTCTT and c.1359delT) were novel. Most patients received timely treatment and had favorable metabolic responses, with reductions in C3, C3/C2 and urine MMA. We obtained 16 records of DQ/IQ assessments. Six patients exhibited normal development, but ten patients suffered from neurological symptoms of varying degrees and had low DQ/IQ scores. Conclusion: Our study contributes toward expanding the knowledge of the genetic basis of mut MMA. The c.914T > C was the most frequent mutation, and four novel mutations were detected. Patients diagnosed by newborn screening and treated at the presymptomatic stage may have better outcomes. However, these limited data do not allow any definitive statements on possible genotype–phenotype correlations that can influence the outcomes of mut MMA. Nonetheless, it is necessary for high-risk families to have early prenatal diagnoses. Keywords: follow-up, isolated methylmalonic acidemia, methylmalonyl-CoA mutase, MUT

Abstract Background Since the inception of newborn screening programs in China in the 1990s, pregnancy among patients with inherited, metabolic disorders has become more common. This study explores the management and outcomes of planned, full-term pregnancies in patients with phenylketonuria (PKU). Method Married patients with PKU from 2012 to 2017 were enrolled to receive prenatal counseling and regular health assessments. Study-related assessments included the timing of Phe-restricted diets, maternal weight gain, gestational age, pregnancy complications, and blood Phe concentrations (both pre-conception and during pregnancy), obstetrical data, and offspring outcomes(e.g. anthropomorphic measurements and developmental quotients [DQs]). Results A total of six offspring were successfully delivered. The mean ± SD (range) age of the mother at delivery was 26.3 ± 4.7 (range: 21.1–32.5) years. The mean duration of Phe control before pregnancy was 5.5 ± 1.3(range: 3.1–6.5) months. During pregnancy, the proportion of blood Phe concentrations within the clinically-recommended target range (120–360 μmol/L) ranged from 63.2–83.5%. Low birth weight (

Background: Maple syrup urine disease (MSUD) is a rare metabolic disorder of autosomal recessive inheritance caused by decreased activity of branched-chain α-ketoacid dehydrogenase complex (BCKD). Mutations in the three genes (BCKDHA, BCKDHB and DBT) are associated with MSUD. Here, we describe the presenting symptoms, clinical course and gene mutation analysis of a Chinese boy with MSUD. Methods: Plasma amino acid analysis was performed by tandem mass spectrometry and the levels of organic acids in urine were measured with gas chromatography-mass spectrometry. The BCKDHB gene was sequenced by Sanger method. Furthermore, the significance of the novel mutations was predicted by Polyphen and Mutationtaster. After diagnosis, the patient was fed with protein-restricted diet to reduce intake of BCAA and was treated with l-carnitine. Metabolic parameters, clinical presentation and mental development were followed up. Results: The patient was diagnosed as MSUD. Two novel BCKDHB mutations (c.523 T > C and c.478-25_552del100) were identified. In silico analysis predicted that the two mutations were “disease causing”. The boy tolerated the treatment well and had symptomatic improvement. He presented with mild hypotonia and had nearly normal DQ scores at the age of 10 months. The two novel mutations resulted in the clinical manifestations of MSUD. Our results may reflect the heterogeneity of the pathogenic variants found in patients with MSUD. Key Words: BCAA, BCKD, BCKDHB, gene mutation, maple syrup urine disease

Cough variant asthma (CVA), as one of bronchitis diseases, features with repeated cough. In clinics, CAV does not show significant abnormal signs, therefore antibiotic therapy can hardly achieve satisfactory treatment effect. With the development of scientific technologies, the correlation between mycoplasma pneumoniae infection and CVA has become a hot research topic in clinics. In clinics, mycoplasma pneumoniae is extensively regarded as major cause for CVA, with complex pathogenic mechanism. The symptoms of CVA is characterized by chronic non abnormal inflammation, normally accompanied with bronchospasm and intestinal infection. Clinical practices show that about 6% of CVA children mainly show continuous cough till midnight during onset period, which is easily to misdiagnosed as bronchitis. Mycoplasma pneumoniae infection is a common disease threatening Children's health in China. With the annual increase of incidence of infantile pneumonia in China, mycoplasma pneumoniae infection has become a major reason leading to the death of child in China. More such mycoplasma pneumoniae infection is a sporadic disease spreading in a small range, and can onset in four seasons, making great impact on living quality and health of children. On this basis, this paper analyzes the correlation between Children's CVA and mycoplasma pneumoniae infection, in the hope of providing valuable reference for clinical treatment. [ABSTRACT FROM AUTHOR]