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Hundreds of NPC1 variants cause highly heterogeneous phenotypes. This study aims to explore the genotype-phenotype correlation of NPC1, especially for missense variants. In a well-characterized cohort, phenotypes are graded into three clinical forms: mild, intermediate, and severe. Missense residue structural location was stratified into three categories: surface, partially, and fully buried. The association of phenotypes with the topography of the amino acid substitution in the protein structure was investigated in our cohort and validated in two reported cohorts. One hundred six unrelated NPC1 patients were enrolled. A significant correlation of genotype-phenotype was found in 81 classified individuals with two or one (the second was null variant) missense variant (p < 0.001): of 25 patients with at least one missense variant of surface (group A), 19 (76%) mild, six (24%) intermediate, and none severe; of 31 cases with at least one missense variant of partially buried without surface variants (group B), 11 (35%) mild, 16 (52%) intermediate, and four (13%) severe; of the remaining 25 patients with two or one buried missense variants (group C), eight (32%) mild, nine (36%) intermediate, and eight (32%) severe. Additionally, 7-ketocholesterol, the biomarker, was lower in group A than in group B (p = 0.024) and group C (p = 0.029). A model was proposed that accurately predicted phenotypes of 72 of 90 (80%), 73 of85 (86%), and 64 of 69 (93%) patients in our cohort, Italian, and UK cohort, respectively. This study proposed a novel genotype-phenotype correlation in NPC1, linking the underlying molecular pathophysiology with clinical phenotype and aiding genetic counseling and evaluation in clinical practice., (© 2023 SSIEM.)

Objective: This study aimed to validate the feasibility of haplotype-based noninvasive prenatal diagnosis (NIPD) of cobalamin C (cblC) deficiency., Method: This method includes three steps: First, targeted sequencing was performed on 21 families affected by cblC deficiency (including the couples and probands). Second, parental haplotypes linked with the pathogenic variant were determined using the genotypes of trios. Then, the fetal haplotypes were inferred through a parental haplotype assisted hidden Markov model (HMM). The NIPD results were confirmed by using the invasive procedures., Results: Twenty-one fetal genotypes were successfully inferred by NIPD including three compound heterozygotes with cblC deficiency, nine heterozygote carriers of cblC deficiency, and nine normal fetuses. The NIPD results were confirmed using the invasive procedures with 100% concordant rate., Conclusion: This result has shown that haplotype-based NIPD of cblC deficiency has high concordant rate and indicated potential clinical utility as a pregnancy diagnosis method for high-risk carrier couples., (© 2019 John Wiley & Sons, Ltd.)

Background: Previous studies have shown that feeding a high-energy formula (HF) to infants after cardiac surgery increases energy intake, with fewer side effects on cardiopulmonary function. However, impacts on weight gain and gastrointestinal function remain unclear., Aims and Objectives: To determine the impact of HF compared with standard formula on weight gain and gastrointestinal tolerance in postoperative infants with congenital heart disease., Design: This was a randomized controlled trial., Methods: The setting of the study was at a 20-bed cardiac intensive care unit at a tertiary children's hospital in China. Study population included infants <1 year of age who underwent cardiac surgery and were allocated to the intervention group (n = 32) or control group (n = 32). The intervention group received HF (100 kcal/100 mL), and the control group received standard formula (67 kcal/100 mL) for 7 days during the stabilized postoperative period at the cardiac intensive care unit. Primary outcomes were weight gain and gastrointestinal intolerance. Secondary outcomes were energy intake and standard intensive care characteristics., Results: Infants who received HF (n = 30) showed less weight loss than those who received standard formula (n = 29); -16 g [95% confidence interval (CI): -74 to 42] versus -181 g (95% CI: -264 to -99), P = 0·001. The evaluation of gastrointestinal intolerance showed that the intervention group had several side effects, such as abdominal distension (n = 1), gastric retention (n = 2) and diarrhoea (n = 1), while the control group had no problems. Enteral energy intake in the intervention group was higher than the control group from day three., Conclusion: Infants after cardiac surgery fed with HF gained more weight but had increased feeding intolerance. However, the feeding intolerance symptoms could be relieved by medication and did not affect feeding advancement., Relevance to Clinical Practice: Paediatric intensive care clinicians should consider gradually increasing the energy density of the formula during feeding and assess feeding intolerance signs in some children with malnutrition after cardiac surgery., (© 2018 British Association of Critical Care Nurses.)

Background: Information concerning inherited metabolic diseases in China is scarce. We investigated the prevalence and age distributions of amino acid, organic acid, and fatty acid oxidation disorders in Chinese patients., Methods: Blood levels of amino acids and acylcarnitines (tandem mass spectrometry) were measured in 18,303 patients with suspected inherited metabolic diseases. Diagnosis was based on clinical features, blood levels of amino acids or acylcarnitines, urinary organic acid levels (gas chromatography-mass spectrometry), and (in some) gene mutation tests., Results: Inherited metabolic diseases were confirmed in 1,135 patients (739 males, 396 females). Median age was 12 months (1 day to 59 years). There were 28 diseases: 12 amino acid disorders (580 patients, 51.1%), with hyperphenylalaninemia (HPA) being the most common; nine organic acidemias (408 patients, 35.9%), with methylmalonic acidemia (MMA) as the most common; and seven fatty acid oxidation defects (147 patients, 13.0%), with multiple acyl-coenzyme A dehydrogenase deficiency (MADD) being the most common. Onset was mainly at 1-6 months for citrin deficiency, 0-6 months for MMA, and in newborns for ornithine transcarbamylase deficiency (OTCD). HPA was common in patients aged 1-3 years, and MADD was common in patients >18 years., Conclusions: In China, HPA, citrin deficiency, MMA, and MADD are the most common inherited disorders, particularly in newborns/infants., (© 2014 Wiley Periodicals, Inc.)