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

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yiming Lin ◽  
Weihua Lin ◽  
Yanru Chen ◽  
Chunmei Lin ◽  
Zhenzhu Zheng ◽  
...  
Keyword(s):  
Intrahepatic Cholestasis ◽  
Autosomal Recessive ◽  
Metabolic Diseases ◽  
Autosomal Recessive Disorder ◽  
Carnitine Deficiency ◽  
Acid Oxidation ◽  
Dual Disorders ◽  
Expanded Newborn Screening ◽  
Primary Carnitine Deficiency ◽  
Citrin Deficiency

Abstract 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. Case presentation Targeted exome sequencing was performed on a Chinese proband, and Sanger sequencing was utilised to validate the detected mutations. The patient who was initially suspected to have PCD based on the NBS results presented with neonatal intrahepatic cholestasis and ventricular septal defect. Further investigations not only confirmed PCD but also revealed the presence of NICCD. Four distinct mutations were detected, including c.51C > G (p.F17L) and c.760C > T (p.R254X) in SLC22A5 as well as c.615 + 5G > A and IVS16ins3kb in SLC25A13. Conclusions This is the first reported case of PCD and NICCD occurring in the same patient. The dual disorders in a newborn broaden our understanding of inherited metabolic diseases. Thus, this study highlighted the importance of further genetic testing in patients presenting with unusual metabolic screening findings.

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 Dilated Cardiomyopathy (DCM) in an Infant Due to Primary Carnitine Deficiency (PCD); A Rare Case

2021 ◽  
pp. 74-77
Author(s):  
Varsha Gajbhiye ◽  
Shubhangi Patil ◽  
Sarika Gaikwad ◽  
Sushma Myadam
Keyword(s):  
Dilated Cardiomyopathy ◽  
Autosomal Recessive ◽  
Work Of Breathing ◽  
Carnitine Deficiency ◽  
Acid Oxidation ◽  
Case Presentation ◽  
Life Threatening ◽  
Prolonged Qt Interval ◽  
Primary Carnitine Deficiency ◽  
2D Echocardiogram

Dilated cardiomyopathy (DCM) is known to have ventricular dilatation and dysfunction in  myocardium. Primary carnitine deficiency (PCD) is a not common but a reversible autosomal recessive phenomenon with supplementation of carnitine. Case presentation- 11-month male child was brought with complain of fever, cough, cold since 7 days and increased work of breathing for 15 days.  2 D echo was done suggestive of dilated cardiomyopathy. His initial investigations; chest Xray revealed significant cardiomegaly electrocardiography, (ECG) showed prolonged QT interval fraction. Patient was treated with syrup carnitine syrup empirically, as there is no way to determine a fatty acid oxidation profile. Repeated 2D echocardiogram (2 D ECHO) was suggestive of recovery. Conclusions: Carnitine deficiency could be the cause of  cardiomyopathy and so treatment of carnitine supplementation can be considered empirically to avoid life-threatening complication related to cardiomyopathy.

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.

scholarly journals A case of atypical systemic primary carnitine deficiency in Saudi Arabia

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Abdulrahman Alghamdi ◽  
Hani Almalki ◽  
Aiman Shawli ◽  
Rahaf Waggass ◽  
Fahad Hakami
Keyword(s):  
Dilated Cardiomyopathy ◽  
Autosomal Recessive ◽  
Acid Metabolism ◽  
Age Of Onset ◽  
Carnitine Deficiency ◽  
Proximal Muscle ◽  
Skeletal Myopathy ◽  
Primary Carnitine Deficiency ◽  
Elevated Transaminases ◽  
Work Up

Systemic primary carnitine deficiency (SPCD) is an autosomal recessive inborn error of fatty acid metabolism caused by a defect in the transporter responsible for moving carnitine across plasma membrane. The clinical features of SPCD vary widely based on the age of onset and organs involved. During infancy, patients might show episodes of hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia. Skeletal myopathy, elevated creatine kinase, and cardiomyopathy are the main manifestations in children with SPCD, while in adults, the disorder is usually manifested as cardiomyopathy, arrhythmias, or fatigability. Here, we report a 5-year-old boy with SPCD that presented as dilated cardiomyopathy with atypical features, such as anemia, respiratory distress, and proximal muscle weakness. This report supports considering carnitine deficiency treatment in the work-up of unexplained pediatric dilated cardiomyopathy.

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 Carnitine Palmitoyltranferase Type 1 Deficiency: A Case Report of Fatty Acid Oxidation Disorder Encephalopathy

2020 ◽  
Author(s):  
Pantea Tajik ◽  
Amir Hossein Goudarzian ◽  
Zeinab Pourzahabi
Keyword(s):  
Case Report ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Autosomal Recessive ◽  
Case Reports ◽  
Autosomal Recessive Disorder ◽  
Acid Oxidation ◽  
Ketotic Hypoglycemia ◽  
Recessive Defect ◽  
Carnitine Palmitoyltransferase 1

Background: Carnitine palmitoyltransferase-1 (CPT-1) deficiency is a rare autosomal recessive disorder of mitochondrial long-chain fatty acid oxidation with fewer than 30 case reports. Case report: A 30-month-old child with fever and loss of consciousness was referred to our hospital. She had symptoms of colds for three days that were treated, but she had anorexia.Her abdomen was soft and hepatomegaly 5 cm below the edge of the rib was detected. According to a neurological consultation, with the probability of a seizure, the patient beganto receive levetiracetam. The patient was treated with sodium benzoate due to her decreased level of consciousness and increased blood ammonia (300). In the acylcarnitine profile, mildlyelevated levels of single acylcarnitine were seen to confirm the diagnosis of CPT-1 deficiency. Conclusions: CPT-1 deficiency is a rare autosomal recessive defect of mitochondrial longchain fatty acid oxidation that presents as an acute “Reye-like” hepatic encephalopathy andnon-ketotic hypoglycemia, developmental delay, and hepatomegaly.

Novel mutations in the SLC25A13 gene in a patient with NICCD and severe manifestations

2015 ◽  
Vol 28 (3-4) ◽  
Author(s):  
Hong Wang ◽  
Sainan Shu ◽  
Chen Chen ◽  
Zhihua Huang ◽  
DaoWen Wang
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Novel Mutations ◽  
Citrin Deficiency

AbstractNeonatal intrahepatic cholestatic due to citrin deficiency (NICCD) is an autosomal recessive disorder caused by mutations in the

scholarly journals Primary Carnitine Deficiency and Autism Spectrum Disorder is there a Relationship?

2021 ◽  
Vol 4 (3) ◽  
Keyword(s):  
Autism Spectrum Disorders ◽  
Genetic Disorder ◽  
Organic Cation Transporter ◽  
Autism Spectrum ◽  
Carnitine Deficiency ◽  
Acid Oxidation ◽  
Carnitine Transporter ◽  
Spectrum Disorders ◽  
Primary Carnitine Deficiency ◽  
Intellectual Deficit

Carnitine plays essential role in energy metabolism .Systemic primary carnitine deficiency is a genetic disorder caused by decreased or absent organic cation transporter type 2 (OCTN2) carnitine transporter activity, resulting in low serum carnitine levels and decreased carnitine accumulation inside cells. The decrease carnitine results in impaired fatty acid oxidation. Primary carnitine deficiency presents a hypoketotic, hypoglycemia and hepatic encephalopathy. Recently, primary carnitine deficiency has been associated with neurodevelopmental disorders including autism spectrum disorders. A seven year-old schoolgirl with intellectual deficit, autistic features and primary carnitine deficiency has been reported. A significant decrease in carnitine levels has been shown in patients with autism and this has been related to the existence of a mitochondrial disease and more severe autism. The early identification of patients with low levels of carnitine or primary carnitine deficiency, with the different methods of measuring free carnitine, including tandem mass spectrometry could help to identify these patients early and achieve an early treatment and better neurological prognosis, because autism spectrum disorders may be preventable in this subgroup. We hope that this paper is useful to neurologists and pediatricians, and may give them more reason to suspect a diagnosis of PCD and autism.

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.

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