Identification of novel compound heterozygous variants in SLC19A2 and the genotype-phenotype associations in thiamine-responsive megaloblastic anemia.

BACKGROUND AND AIMS: Thiamine-responsive megaloblastic anemia (TRMA), caused by SLC19A2 loss-of-function variants, is characterized by the triad of megaloblastic anemia, progressive sensorineural deafness, and non-type 1 diabetes mellitus. Here, we present the case of a Chinese infant with two novel variants segregating in compound heterozygous form in SLC19A2 and reviewed genotype-phenotype associations (GPAs) in patients with TRMA. MATERIALS AND METHODS: Whole-exome sequencing was performed to establish a genetic diagnosis. The clinical manifestations and genetic variants were collected by performing a literature review. The bioinformatics software SIFT, PolyPhen2, and Mutation Taster was applied to predict variant effects and analyze GPAs. RESULTS: Two novel variants segregating in compound heterozygous form in SLC19A2 (NM_006996.2: exon2:c.336_363del:p.W112fs; exon2:c.358G>T:p.G120X) was identified. Thiamine supplementation corrected anemia and diabetes mellitus but did not improve the hearing defect. In the literature, 183 patients with TRMA with 74 variants in SLC19A2 have been reported, with high incidence in the Middle East, South Asia, and the northern Mediterranean. Patients with biallelic premature termination codon variants presented with more severe phenotypes, and truncating sites on extracellular domains was a protective factor for the hemoglobin level at diagnosis. CONCLUSION: Two novel compound heterozygous variants (NM_006996.2: exon2:c.336_363del:p.W112fs; exon2:c.358G>T:p.G120X) were identified, and GPAs in TRMA indicated the predictability of clinical manifestations.

The association of auditory integration training in children with autism spectrum disorders among Chinese: a meta-analysis.

Randomized controlled trials (RCTs) have reported an inconsistent relationship about the auditory integration training (AIT) in children with autism spectrum disorders (ASD) among Chinese. The current study was to investigate the efficacy of AIT for children with ASD compared with those in control group by using meta-analysis. Relevant trials published were identified by an electronic search of PubMed, CENTRAL, EMBASE, WanFang, CNKI, and SinoMed databases up to December 31, 2017. Outcome of interest included childhood autism rating scale (CARS), autism behavior checklist (ABC), intelligence quotient (IQ), and autism treatment evaluation checklist (ATEC). Standardized mean difference (SMD) with 95% confidence intervals (CIs) was calculated using a random-effect model. Thirteen RCTs with 976 children with ASD were included for analysis. The pooled SMD showed that children with ASD had significantly lower ABC scores [summary SMD = -0.58, 95%CI = -0.79 to -0.38] and ATEC scores [summary SMD = -0.75, 95%CI = -1.05 to -0.45] in AIT group compared with that in control group. The analysis of pooled statistics put forward AIT could increase the IQ score when compared with that in control group [summary SMD = 0.59, 95%CI = 0.41-0.77]. A negative association was found about CARS scores between AIT group and control group. No publication bias was found and no single study had essential effect on the pooled results. In conclusions, AIT can reduce the score of ABC and ATEC and can increase the IQ score among children with ASD in Chinese. Therefore, it is recommended for Chinese children with ASD to receive AIT.

Growth hormone-IGF-I axis and growth velocity in Chinese children with type 1 diabetes mellitus.

OBJECTIVE: To elucidate hormonal disturbances in patients with type 1 diabetes mellitus (DM1) with and without growth retardation. METHODS: Patients with DM1 were divided into two groups, group A consisted of 14 patients with poor growth, and group B consisted of 24 patients with normal growth. Serum IGF-I, IGFBP-3, basal and stimulated GH, and HbA1c were measured. RESULTS: Serum IGF-I and IGFBP-3 concentrations were significantly decreased in group A versus both groups B and controls in Tanner stages I-III; in addition, these measurements in group B were significantly lower compared to controls in Tanner stages II and III, but there was no significant difference in prepuberty. Both basal and peak serum GH were attenuated significantly in group A versus group B. Basal serum GH in group B (normal growth DM1) was significantly elevated versus the controls. There was an unambiguous negative linear regression between IGF-I and mean HbA1c in patients with DM1. CONCLUSIONS: Growth retardation in patients with DM1 is associated with an abnormal GH-IGF-I axis and poor glycemic control.