scholarly journals Newborn Screening and Genetic Analysis Identify Six Novel Genetic Variants for Primary Carnitine Deficiency in Ningbo Area, China

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangchun Yang ◽  
Qiong Li ◽  
Fei Wang ◽  
Lulu Yan ◽  
Danyan Zhuang ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Dna Analysis ◽  
Autosomal Recessive Disorder ◽  
Carnitine Deficiency ◽  
Compound Heterozygous ◽  
Clinical Value ◽  
Birth Prevalence ◽  
Carnitine Transporter ◽  
Novel Variants ◽  
Primary Carnitine Deficiency

Primary carnitine deficiency (PCD) is an autosomal recessive disorder that could result in sudden death. It is caused by a defect in the carnitine transporter encoded by SLC22A5 (Solute Carrier Family 22 Member 5, MIM:603377). Currently, a number of variants in SLC22A5 have been identified, however, the PCD prevalence and its variants in Ningbo area are unclear. In this study, we screened 265,524 newborns by using tandem mass spectrometry. Variants in SLC22A5 were further detected by next-generation sequencing in individuals with abnormal free carnitine levels (C0). We identified 53 newborns with abnormal C0 levels and 26 with variants in SLC22A5. Among them, 16 with compound heterozygous or homozygous variants in SLC22A5 were diagnosed with PCD, suggesting the PCD birth prevalence in Ningbo city was 1/16,595. Moreover, the C0 level was significantly (P = 0.013) higher in PCD patients than in those with one variant. Besides, the c.1400C > G (p. S467C) and c.51C > G (p. F17L) variants were the most frequent and six novel variants are all predicted to be damaging. This study reports the largest PCD patients in Ningbo area by newborn screening and expands the variant spectrum of SLC22A5. Our findings demonstrate the clinical value of combining NBS program results with DNA analysis for the diagnosis of PCD.

scholarly journals Biochemical And Genetic Characteristics of Patients With Primary Carnitine Deficiency Identified Through Newborn Screening

2021 ◽  
Author(s):  
Yiming Lin ◽  
Bangbang Lin ◽  
Yanru Chen ◽  
Zhenzhu Zheng ◽  
Qingliu Fu ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Allele Frequency ◽  
Large Scale ◽  
Autosomal Recessive Disorder ◽  
Carnitine Deficiency ◽  
Acid Oxidation ◽  
Genetic Characteristics ◽  
Pathogenic Variants ◽  
Southern Chinese ◽  
Primary Carnitine Deficiency

Abstract Background: Primary carnitine deficiency (PCD) is an autosomal recessive disorder of the 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 by NBS.Results: A total of 548,247 newborns were screened for PCD between January 2014 and June 2021, 1714 newborns had low free carnitine (C0) levels were called back and forty-nine patients were diagnosed with PCD. The latest incidence rate in Quanzhou, China was estimated to be 1 in 11,189 newborns. NBS results showed that all patients had varying degrees of decreased C0 levels, while seven patients exhibited normal C0 levels during recall review. All patients harbored biallelic pathogenic variants in the SLC22A5 gene. Nineteen distinct SLC22A5 variants were detected in the 49 patients, most of the detected variants were clustered in exons 1, 4, and 7. The top eight variants together had an allele frequency of 86.73%. The most common variant was c.760C>T (p.R254*) with an allele frequency of 31.63%, followed by c.51C>G (p.F17L) (17.35%) and c.1400C>G (p.S467C) (16.33%). The C0 level of patients with N/N genotype was significantly lower than that of M/M group. The C0 level of patients with genotypes of R254*/R254* and R254*/F17L were far lower than patients with genotype of R254*/S467C.Conclusions: This study presented more than 500,000 NBS data with the latest incidence of 1:11,189 in Quanzhou area. The SLC22A5 variant spectrum in the selected southern Chinese population was updated. Patients with null variants were associated with low C0 levels. It is necessary to combine genetic testing to improve screening efficiency due to PCD patients may have normal C0 levels during NBS and recall review.

Primary systemic carnitine deficiency: a Turkish case with a novel homozygous SLC22A5 mutation and 14 years follow-up

2015 ◽  
Vol 28 (9-10) ◽  
Author(s):  
Berna Seker Yilmaz ◽  
Deniz Kor ◽  
Neslihan Onenli Mungan ◽  
Sevcan Erdem ◽  
Serdar Ceylaner
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Carnitine Deficiency ◽  
Carnitine Transporter ◽  
Hypoglycemic Encephalopathy ◽  
Primary Carnitine Deficiency ◽  
Turkish Case ◽  
Systemic Carnitine Deficiency

AbstractSystemic primary carnitine deficiency is an autosomal recessive disorder caused by the deficiency of carnitine transporter. Main features are cardiomyopathy, myopathy and hypoglycemic encephalopathy. We report a Turkish case with a novel

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

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yiming Lin ◽  
Bangbang Lin ◽  
Yanru Chen ◽  
Zhenzhu Zheng ◽  
Qingliu Fu ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Allele Frequency ◽  
Large Scale ◽  
Autosomal Recessive Disorder ◽  
Carnitine Deficiency ◽  
Acid Oxidation ◽  
Genetic Characteristics ◽  
Pathogenic Variants ◽  
Southern Chinese ◽  
Primary Carnitine Deficiency

Abstract 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. Results A total of 548 247 newborns were screened for PCD between January 2014 and June 2021; 1714 newborns with low free carnitine (C0) levels were called back and 49 patients were diagnosed with PCD. The latest incidence rate in Quanzhou, China, was estimated to be 1 in 11 189 newborns. NBS results showed that the 49 patients had varying degrees of decreased C0 levels, whereas seven patients exhibited normal C0 levels during the recall review. All patients harbored biallelic pathogenic variants of the SLC22A5 gene. Nineteen distinct SLC22A5 variants were detected in these 49 patients, and most of the detected variants were clustered in exons 1, 4, and 7. The top eight variants had an allele frequency of 86.73%. The most common variant was c.760C > T (p.R254*) with an allele frequency of 31.63%, followed by c.51C > G (p.F17L) (17.35%) and c.1400C > G (p.S467C) (16.33%). The C0 level of patients with the N/N genotype was significantly lower than that of the M/M group. The C0 levels of patients with genotypes of R254*/R254* and R254*/F17L were far lower than those of patients with the R254*/S467C genotype. Conclusions This study presented more than 500,000 NBS data with the latest incidence of 1:11 189 in the Quanzhou area. The SLC22A5 variant spectrum in the selected southern Chinese population has been updated. Patients with null variants were associated with low C0 levels. Combining NBS with genetic testing is critical to improve screening efficiency because patients with PCD may have normal C0 levels during NBS and recall review.

Endocardial fibroelastosis and primary carnitine deficiency due to a defect in the plasma membrane carnitine transporter

1996 ◽  
Vol 19 (3) ◽  
pp. 243-246 ◽  
Author(s):  
Michael J. Bennett ◽  
Daniel E. Hale ◽  
Rodney J. Pollitt ◽  
Sadick Variend ◽  
Charles A. Stanley
Keyword(s):  
Plasma Membrane ◽  
Carnitine Deficiency ◽  
Endocardial Fibroelastosis ◽  
Carnitine Transporter ◽  
Primary Carnitine Deficiency

scholarly journals Maternal systemic primary carnitine deficiency uncovered by newborn screening: Clinical, biochemical, and molecular aspects

2009 ◽  
Vol 12 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Ayman W El-Hattab ◽  
Fang-Yuan Li ◽  
Joseph Shen ◽  
Berkley R Powell ◽  
Erawati V Bawle ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Carnitine Deficiency ◽  
Primary Carnitine Deficiency ◽  
Molecular Aspects

scholarly journals Primary carnitine deficiency – diagnosis after heart transplantation: Better late than never!

2020 ◽  
Author(s):  
Sarah Catharina Grünert ◽  
Sara Tucci ◽  
Anke Schumann ◽  
Meike Schwendt ◽  
Gwendolyn Gramer ◽  
...  
Keyword(s):  
Pilot Study ◽  
Heart Transplantation ◽  
Newborn Screening ◽  
Cardiac Death ◽  
Clinical Symptoms ◽  
Carnitine Deficiency ◽  
Carnitine Supplementation ◽  
Expanded Newborn Screening ◽  
Patients At Risk ◽  
Primary Carnitine Deficiency

Abstract Background Primary carnitine deficiency due to mutations in the OCTN2 gene is a rare but well-treatable metabolic disorder that puts patients at risk for metabolic decompensations, skeletal and cardiac myopathy and sudden cardiac death. Results We report on a 7-year-old boy diagnosed with primary carnitine deficiency 2 years after successful heart transplantation thanks his younger sister’s having been identified via expanded newborn screening during a pilot study evaluating an extension of the German newborn screening panel. Conclusion As L-carnitine supplementation can prevent and mostly reverse clinical symptoms of primary carnitine deficiency, all patients with cardiomyopathy should be investigated for primary carnitine deficiency even if newborn screening results were unremarkable.

scholarly journals The genetic basis of classical galactosaemia in Polish patients

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Aleksandra Jezela-Stanek ◽  
Anna Bauer ◽  
Katarzyna Wertheim-Tysarowska ◽  
Jerzy Bal ◽  
Agnieszka Magdalena Rygiel ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Genetic Basis ◽  
Dna Analysis ◽  
Current Knowledge ◽  
Autosomal Recessive Disorder ◽  
Molecular Characteristics ◽  
Compound Heterozygous ◽  
Classic Galactosemia ◽  
Pathogenic Variants ◽  
Molecular Etiology

AbstractClassic galactosemia (OMIM #230400) is an autosomal recessive disorder caused by homozygous or compound heterozygous pathogenic variants in the galactose-1-phosphate uridylyltransferase gene (GALT; 606999) on chromosome 9p13. Its diagnosis is established by detecting elevated erythrocyte galactose-1-phosphate concentration, reduced erythrocyte galactose-1-phosphate uridylyltransferase (GALT) enzyme activity. Biallelic pathogenic variants in the GALT gene is confirmed by DNA analysis. Our paper presents molecular characteristics of 195 Polish patients diagnosed with galactosemia I, intending to expand the current knowledge of this rare disease's molecular etiology. To the best of our knowledge, the described cohort of galactosemia patients is the largest single-center cohort presented so far.

Sign in / Sign up

Export Citation Format

Share Document