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 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 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.

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 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 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.

scholarly journals Primary systemic carnitine deficiency is caused by mutations in a carnitine transporter OCTN2

1999 ◽  
Vol 79 ◽  
pp. 108
Author(s):  
Jun-ichi Nezu ◽  
Ikumi Tamai ◽  
Asuka Oku ◽  
Rikiya Ohashi ◽  
Yoshimichi Sai ◽  
...  
Keyword(s):  
Carnitine Deficiency ◽  
Carnitine Transporter ◽  
Systemic Carnitine Deficiency

Longitudinal Follow-up of Malignant Osteopetrosis by Skeletal Radiographs and Restriction Fragment Length Polymorphism Analysis After Bone Marrow Transplantation

PEDIATRICS ◽  
1992 ◽  
Vol 90 (6) ◽  
pp. 986-989
Author(s):  
ROBERT E. SCHROEDER ◽  
F. LEONARD JOHNSON ◽  
MICHAEL J. SILBERSTEIN ◽  
WILMA L. NEUMAN ◽  
JEANNE M. HOAG ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Fragment Length Polymorphism ◽  
Autosomal Recessive Disorder ◽  
Polymorphism Analysis ◽  
Newborn Period ◽  
Normal Bone ◽  
Malignant Osteopetrosis ◽  
Osteoclast Function ◽  
Infantile Malignant Osteopetrosis

Infantile malignant osteopetrosis is a rare autosomal recessive disorder characterized by presentation in the first months of life with manifestations related to an underlying defect in osteoclast function. Abnormal osteoclast activity paired with normal bone formation by osteoblasts leads to development of densely sclerotic fragile bones. Encroachment on the marrow cavities by hyperostotic bone results in profound anemia and thrombocytopenia, with extramedullary ullary hematopoiesis and hypersplenism. Deficits in immune function can lead to presentation with overwhelming sepsis in the newborn period. Narrowing of the optic and auditory foramina can lead to progressive blindness and hearing loss. Until recently, the prognosis for this disorder had been uniformly dismal with death usually occurring within a few months.l-3

THE IMPORTANCE OF CARNITINE AND ITS METABOLISM IN NEWBORN: LITERATURE REVIEW AND CLINICAL CASE

2021 ◽  
Vol 8 (2) ◽  
pp. 100-103
Author(s):  
Тetiana Znamenska ◽  
Оlha Vorobiova ◽  
Тetiana Holota ◽  
Yurii Marushko ◽  
Valerii Pokhylko
Keyword(s):  
Clinical Case ◽  
Clinical Manifestations ◽  
Rare Condition ◽  
Carnitine Deficiency ◽  
Metabolic Decompensation ◽  
Pathological Conditions ◽  
Primary Carnitine Deficiency ◽  
And Function ◽  
Genetically Determined ◽  
Systemic Carnitine Deficiency

Aim: To analyze the literature on the processes of formation of endogenous and exogenous carnitine, its metabolism and function in the newborn. Material and methods: The literature data and international clinical recommendations for pathological conditions leading to primary and secondary carnitine deficiency have been retrospectively analyzed. A clinical case of a child with suspected systemic carnitine deficiency is presented. Conclusions: Depending on the reasons that led to carnitine deficiency, there are primary and secondary carnitine deficiency. Primary carnitine deficiency is a rare condition that can lead to metabolic decompensation, muscular and cardiac myopathy, and sudden death. Secondary carnitine deficiency can be caused by a genetically determined congenital metabolic defect, insufficient substrate intake, acquired disorder, immaturity of the biochemical pathway in premature infants, renal failure or iatrogenic exposure. Familiarization with the main causes of carnitine deficiency in newborns will more effectively detect and correct the clinical manifestations of this condition.

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