Incorporating second-tier genetic screening for multiple acyl-CoA dehydrogenase deficiency.

Background: Newborn screening (NBS) for multiple acyl-CoA dehydrogenase deficiency (MADD) has poor sensitivity. This study aimed to evaluate the feasibility of incorporating second-tier genetic screening for MADD.

Methods: A total of 453,390 newborns were screened for inherited metabolic disorders using tandem mass spectrometry from January 2017 to May 2022.

Newborn screening and genetic features of patients with hyperphenylalaninemia in a southern Chinese population.

Background And Aims: Hyperphenylalaninemia (HPA) is the most common congenital amino acid metabolism-related defect, but its incidence differs substantially between northern and southern China. We aimed to elucidate the incidence, proportion, and genetic features of HPA in a southern Chinese population.

Materials And Methods: We analyzed the HPA screening results for 580,460 newborns from 2014 to 2021.

Three Novel and One Potential Hotspot Variants in Chinese Patients With Carnitine Palmitoyltransferase 1A Deficiency.

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is an inherited disorder of mitochondrial fatty acid β-oxidation that impairs fasting ketogenesis and gluconeogenesis in the liver. Few studies implementing newborn screening (NBS) for CPT1A deficiency in the Chinese population have been reported. This study aimed to determine the biochemical, clinical, and genetic characteristics of patients with CPT1A deficiency in China.

Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening.

Background: Primary carnitine deficiency (PCD) is an autosomal recessive disorder of carnitine transportation that leads to impaired fatty acid oxidation. Large-scale studies on newborn screening (NBS) for PCD are limited. This study aimed to investigate the biochemical and genetic characteristics of patients with PCD detected through NBS.

Biochemical and molecular features of Chinese patients with glutaric acidemia type 1 detected through newborn screening.

Background: Glutaric acidemia type 1 (GA1) is a treatable disorder affecting cerebral organic acid metabolism caused by a defective glutaryl-CoA dehydrogenase (GCDH) gene. GA1 diagnosis reports following newborn screening (NBS) are scarce in the Chinese population. This study aimed to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 identified through NBS.

Newborn screening and molecular features of patients with multiple acyl-CoA dehydrogenase deficiency in Quanzhou, China.

Objectives: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid and choline metabolism. Late-onset MADD is caused by mutations and is the most common lipid storage myopathy in China. However, few patients with MADD have been identified through newborn screening (NBS).

Increased detection of primary carnitine deficiency through second-tier newborn genetic screening.

Background: Newborn screening for primary carnitine deficiency (NBS) is commonly implemented worldwide; however, it has poor sensitivity. This study aimed to evaluate the feasibility of improving screening by including a second-tier genetic assay.

Results: An Agena iPLEX assay was developed to identify 17 common SLC22A5 mutations in Chinese populations and was applied in NBS as a second-tier screening.

Combined primary carnitine deficiency with neonatal intrahepatic cholestasis caused by citrin deficiency in a Chinese newborn.

Background: Primary carnitine deficiency (PCD) is an autosomal recessive disorder affecting the carnitine cycle and resulting in defective fatty acid oxidation. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive disorder and one of the main causes of inherited neonatal cholestasis. Both PCD and NICCD are included in the current expanded newborn screening (NBS) targets.

Clinical, biochemical, and genetic analysis of a Chinese Han pedigree with holocarboxylase synthetase deficiency: a case report.

Background: Holocarboxylase synthetase (HLCS) deficiency is a rare inborn disorder of biotin metabolism, which results in defects in several biotin-dependent carboxylases and presents with metabolic ketoacidosis and skin lesions.

Case Presentation: In this paper, we report a Chinese Han pedigree with HLCS deficiency diagnosed by using next-generation sequencing and validated with Sanger sequencing of the HLCS and BTD genes. The Chinese proband carries the common missense mutation c.

Newborn screening and genetic characteristics of patients with short- and very long-chain acyl-CoA dehydrogenase deficiencies.

Background And Aims: Acyl-CoA dehydrogenase deficiencies are a group of mitochondrial fatty-acid oxidation disorders rarely reported in mainland China. We assessed the biochemical and genetic characteristics of patients with short- and very-long-chain-acyl-CoA dehydrogenase deficiencies (SCADD/VLCADD) discovered through newborn screening.

Materials And Methods: We investigated the effects of genetic variations on protein function using in silico prediction and structural modelling.

Newborn screening for isovaleric acidemia in Quanzhou, China.

Background: Isovaleric acidemia (IVA) is a rare autosomal recessive disorder of leucine metabolism caused by a defective isovaleryl-CoA dehydrogenase (IVD) gene. Reports of IVA diagnoses following newborn screening (NBS) in the Chinese population are few.

Methods: We investigated the biochemical, clinical, and molecular profiles of 5 patients with IVA in China.

Clinical and genetic analysis of five Chinese patients with urea cycle disorders.

Background: The urea cycle plays a key role in preventing the accumulation of toxic nitrogenous waste products, including two essential enzymes: ornithine transcarbamylase (OTC) and argininosuccinate lyase (ASL). Ornithine transcarbamylase deficiency (OTCD) results from mutations in the OTC. Meanwhile, argininosuccinate lyase deficiency (ASLD) is caused by mutations in the ASL.

[Characteristics of gene variants among patients with hyperphenylalaninemia from Quanzhou region of Fujian province].

Objective: To explore the spectrum of genetic variants among patients with hyperphenylalaninemia (HPA) from Quanzhou area of Fujian province.

Methods: For 63 children affected with HPA, next generation sequencing was used to identify potential variants in PAH, PTS, PCBD1, QDPR, SPR and GCH1 genes.

Results: Fifty two variants underlying phenylalanine hydroxylase deficiency (PAHD) and 13 variants underlying 6-pyruvoyl tetrahydropterin synthase deficiency (PTPSD) were identified.

Biochemical, Clinical, and Genetic Characteristics of Short/Branched Chain Acyl-CoA Dehydrogenase Deficiency in Chinese Patients by Newborn Screening.

Short/branched chain acyl-CoA dehydrogenase deficiency (SBCADD) is an autosomal recessive disorder of impaired isoleucine catabolism caused by mutations in the gene. There are limited SBCADD cases worldwide and to date no Chinese patients with SBCADD have been reported. The aim of this study was to investigate the biochemical, clinical information, and genotypes of twelve patients with SBCADD in China for the first time.

Citrullinemia type I is associated with a novel splicing variant, c.773 + 4A > C, in ASS1: a case report and literature review.

Background: Citrullinemia type I (CTLN1) is a rare autosomal recessive disorder of the urea cycle caused by a deficiency in the argininosuccinate synthetase (ASS1) enzyme due to mutations in the ASS1 gene. Only a few Chinese patients with CTLN1 have been reported, and ASS1 gene mutations have been identified sporadically in China.

Case Presentation: A Chinese family with one member affected with mild CTLN1 was enrolled.

Expanded newborn screening for inherited metabolic disorders and genetic characteristics in a southern Chinese population.

To evaluate the incidence, disease spectrum, and genetic characteristics of inherited metabolic disorders (IMDs) of newborns in Quanzhou area, China. We analyze the expanded newborn screening results of IMDs detected by tandem mass spectrometry (MS/MS) during 5 years. Suspected positive patients were diagnosed through next-generation sequencing and validated by Sanger sequencing.

Clinical, biochemical and genetic analysis of Chinese patients with isobutyryl-CoA dehydrogenase deficiency.

Isobutyryl-CoA dehydrogenase deficiency (IBDHD) is a rare autosomal recessive metabolic disorder related to valine catabolism and results from variants in ACAD8. Here, we present the clinical, biochemical, and genotypes of seven patients with IBDHD in China for the first time. Five patients remained asymptomatic during follow-up, whereas one juvenile had speech delay and one newborn exhibited clinical symptoms.

Mild clinical features of isolated methylmalonic acidemia associated with a novel variant in the MMAA gene in two Chinese siblings.

Background: Methylmalonic acidemia (MMA) is an autosomal recessive inherited disorder caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut- enzymatic subtype, respectively); a defect in the transport or synthesis of its cofactor, adenosyl-cobalamin (cblA, cblB, or cblD-MMA); or deficiency of the enzyme methylmalonyl-CoA epimerase. The cblA type of MMA is very rare in China. This study aimed to describe the biochemical, clinical, and genetic characteristics of two siblings in a Chinese family, suspected of having the cblA-type of MMA.

[Detection of GCDH mutations in five Chinese patients with glutaric acidemia type I].

OBJECTIVE To detect potential mutations of GCDH gene in five patients with glutaric acidemia type I (GA-I). METHODS Genomic DNA was extracted from peripheral blood samples from the patients. The 11 exons and their flanking sequences of the GCDH gene were amplified with PCR and subjected to direct sequencing.

A novel compound heterozygous variant identified in GLDC gene in a Chinese family with non-ketotic hyperglycinemia.

Background: Non-ketotic hyperglycinemia (NKH) is a rare, devastating autosomal recessive disorder of glycine metabolism with a very poor prognosis. Currently, few studies have reported genetic profiling of Chinese NKH patients. This study aimed to identify the genetic mutations in a Chinese family with NKH.

[Mutational analysis of ASS1, ASL and SLC25A13 genes in six Chinese patients with citrullinemia].

Objective: To detect potential mutations in six patients with citrullinemia.

Methods: Genomic DNA was extracted from peripheral blood samples from the patients. Mutations of the ASS1, ASL and SLC25A13 genes were screened using microarray genotyping combined with direct sequencing.

[Mutational analysis of SLC22A5 gene in eight patients with systemic primary carnitine deficiency].

Objective: To investigate the mutations of SLC22A5 gene in patients with systemic primary carnitine deficiency (CDSP).

Methods: High liquid chromatography tandem mass spectrometry (HPLC/MS/MS) was applied to screen congenital genetic metabolic disease and eight patients with CDSP were diagnosed among 77 511 samples. The SLC22A5 gene mutation was detected using massarray technology and sanger sequencing.