Here we reported the first Chinese case of primary vaginal and pelvic lymphatic malformations who was diagnosed during childhood.To date, 14 reports of the primary lymphatic malformations of perineum in children were reported worldwide, and only 3 patients had lesions involving the vagina characterized with chronic vaginal discharge or mucosal lesions

Background: Isolated methylmalonic acidemia (MMA), an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type MMA). Because no universal consensus was made on whether mut-type MMA should be included in newborn screening (NBS), we aimed to compare the outcome of this disorder detected by NBS with that detected clinically and investigate the influence of NBS on the disease course. Methods: In this study, 168 patients with mut-type MMA diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome. Results: Among patients diagnosed through NBS, 77 patients (45.8%) remained asymptomatic and 87 patients (53.4%) showed favorable neurocognitive outcomes. In contrast with individuals diagnosed clinically, only 30 cases (16.2%) developed healthily. In our comparison of patients whether detected by NBS, the age at diagnosis, the incidence of disease onset, the responsiveness of vitamin B12, age at the start of vitamin B12 treatment, levels of biochemical features before and after treatment, and the long-term prognosis were remarkably different ( P<0.01). The presence of disease onset and the blood C3/C2 ratio were more associated with poor outcomes of patients whether identified by NBS. Importantly, after considering NBS, the odd ratio of disease onset for poor outcome decreased and the unresponsiveness to vitamin B12 increased. Conclusion: Through preventing major disease-related events and allowing an earlier treatment initiation, NBS is beneficial for the prognosis of infants with mut-type MMA.

Genome sequencing(GS) has been applied in the diagnosis of global developmental delay(GDD)/intellectual disability(ID). However, the performance in those with inconclusive results from chromosomal microarray analysis(CMA) and exome sequencing(ES) is unknown. We recruited 100 pediatric GDD/ID patients from multiple sites in China from February 2018 to August 2020 for GS. Patients have received at least one genomic diagnostic test prior to enrollment. Reanalysis of CMA/ES data was performed. The yield of GS was calculated and explanations for missed diagnoses by CMA/ES were investigated. Clinical utility was assessed by interviewing the parents by phone. The overall diagnostic yield of GS was 23%. Seven families could have been solved with reanalysis of ES data. 13 families were missed by previous CMA/ES due to improper method. Three remained unsolved after ES reanalysis due to allele dropout, complex variants missed by ES, and a CNV in untranslated regions. Follow-up of the diagnosed families revealed that nine families experienced changes in clinical management, including identification of targeted treatments, cessation of unnecessary treatment, and considerations for family planning. GS demonstrated high diagnostic yield and clinical utility in this cohort of undiagnosed GDD/ID patients, detecting a wide range of variant types of different sizes in a single workflow.