• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

Systemic Primary Carnitine Deficiency

Synonyms: CDSP, CUD, Carnitine Uptake Defect
, MD, FAAP, FACMG
Assistant Professor of Child Health & Director of Biochemical Genetics Laboratory
Division of Medical Genetics
Department of Child Health
University of Missouri Health Care
Columbia, Missouri

Initial Posting: .

Summary

Disease characteristics. Systemic primary carnitine deficiency (CDSP) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. It encompasses a broad clinical spectrum including:

  • Metabolic decompensation in infancy typically presenting between age three months and two years with episodes of hypoketotic hypoglycemia, poor feeding, irritability, lethargy, hepatomegaly, elevated liver transaminases, and hyperammonemia triggered by fasting or common illnesses such as upper respiratory tract infection or gastroenteritis;
  • Childhood myopathy involving heart and skeletal muscle with onset between age two and four years;
  • Fatigability in adulthood; or
  • Lack of symptoms.

The latter two categories often include mothers diagnosed with CDSP after newborn screening has identified low carnitine levels in their infants.

Diagnosis/testing. Plasma carnitine levels are extremely reduced in CDSP. The diagnosis is confirmed by the demonstration of reduced fibroblast carnitine transport or biallelic mutations in SLC22A5, the only gene in which mutations are known to cause CDSP.

Management. Treatment of manifestations: Metabolic decompensation and skeletal and cardiac muscle functions improve with 100-400 mg/kg/day oral levocarnitine (L-carnitine) if it is started before irreversible organ damage occurs. Hypoglycemic episodes are treated with intravenous dextrose infusion; cardiomyopathy requires management by specialists in cardiology.

Prevention of primary manifestations: The manifestations of CDSP can be prevented by use of oral L-carnitine supplementation to maintain normal plasma carnitine concentrations.

Surveillance: Suggested: (1) echocardiogram and electrocardiogram: annually during childhood and less frequently in adulthood; (2) plasma carnitine concentration: monitor frequently until levels reach the normal range, then, measure three times a year during infancy and early childhood, twice a year in older children, and annually in adults; (3) serum creatine kinase concentration and liver transaminases: consider measuring during acute illnesses.

Agents/circumstances to avoid: Fasting longer than age-appropriate periods.

Evaluation of relatives at risk: Measure plasma carnitine levels in sibs of an affected individual.

Pregnancy management: Pregnant women with CDSP require close monitoring of plasma carnitine levels and increased carnitine supplementation as needed to maintain normal plasma carnitine levels.

Genetic counseling. CDSP is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal diagnosis for pregnancies at increased risk are possible if the disease-causing mutations in the family are known.

Diagnosis

Clinical Diagnosis

Systemic primary carnitine deficiency (CDSP) should be considered in the following clinical situations:

  • Infants with hypoketotic hypoglycemic episodes that may be associated with hepatomegaly, elevated transaminases, and hyperammonemia
  • Children with skeletal myopathy and/or elevated serum concentration of creatine kinase (CK).
  • Children with cardiomyopathy
  • Adults with unexplained fatigability
  • Sudden death

Testing

Plasma carnitine levels. Plasma free, acylated, and total (the sum of free and acylated) carnitine levels in affected individuals are extremely reduced (i.e., <10% of controls) [Scaglia et al 1999, Longo et al 2006].

Urine organic acid analysis. Nonspecific dicarboxylic aciduria has been reported in some affected individuals [Scaglia et al 1998].

Fibroblast carnitine transport (uptake). Carnitine transport in skin fibroblasts from affected individuals is typically reduced below 10% of control rates [Roe & Ding 2001, Longo et al 2006].

Newborn screening. Newborn screening using tandem mass spectrometry (MS/MS) detects low levels of free carnitine (C0) [Wilcken et al 2001] and can identify:

Heterozygous carriers. Heterozygous carriers usually have about 50% carnitine transport activity in fibroblasts and can have borderline low plasma carnitine levels [Scaglia et al 1998]. However, normal plasma carnitine levels have been reported in some heterozygous carriers. Because the diet, which provides about 75% of the daily requirement of carnitine, may play a role modulating carnitine levels, plasma carnitine levels are not a reliable indicator for heterozygous carrier status; thus, either molecular testing or fibroblast carnitine transport assay is needed to determine carrier status [El-Hattab et al 2010].

Molecular Genetic Testing

Gene. SLC22A5 is the only gene in which mutations are known to cause systemic primary carnitine deficiency.

Clinical testing

  • Sequence analysis. In one study, SLC22A5 sequencing performed in 70 infants with low carnitine levels detected by newborn screening identified two mutations in 23 infants and one mutation in 25 infants; no mutations were detected in 22 infants [Li et al 2010].

Table 1. Summary of Molecular Genetic Testing Used in Systemic Primary Carnitine Deficiency

Gene SymbolTest MethodMutations DetectedMutation Detection Frequency by Test Method 1
SLC22A5Sequence analysisSequence variants 2~70% 3
Deletion / duplication analysis 4Exonic or whole-gene deletionsUnknown 5

1. The ability of the test method used to detect a mutation that is present in the indicated gene

2. Mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations; typically, exonic or whole-gene deletions/duplications are not detected.

3. Sequence analysis of the coding regions and the flanking intronic sequences of SLC22A5 can detect at least one mutation in approximately 70% of affected individuals [Li et al 2010].

4. Testing that identifies deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; a variety of methods including quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), or targeted chromosomal microarray analysis (gene/segment-specific) may be used. A full chromosomal microarray analysis that detects deletions/duplications across the genome may also include this gene/segment.

5. The frequency of large deletions or duplications is unknown, but appears to be low. One out of 26 affected individuals tested by oligonucleotide array CGH was found to have a large deletion encompassing all of SLC22A5 [Li et al 2010].

Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.

Information on specific allelic variants may be available in Molecular Genetics (see Table A and/or Pathologic allelic variants).

Testing Strategy

To confirm/establish the diagnosis in a proband. After the finding of low plasma carnitine levels on a newborn screening assay, in a symptomatic individual, or in an asymptomatic at-risk relative, the diagnosis of CDSP can be confirmed by:

Carrier testing for at-risk relatives requires prior identification of the disease-causing mutations in the family.

Note: (1) Carriers are heterozygotes for this autosomal recessive disorder and are not at risk of developing the disorder. (2) Heterozygotes usually have about 50% carnitine transport activity in fibroblasts [Scaglia et al 1998]. (3) Normal or borderline low plasma carnitine levels can be seen in heterozygous carriers. Therefore, plasma carnitine analysis alone is not sufficient to determine an individual’s carrier status and fibroblast carnitine transport assay or molecular genetic testing is needed to confirm the carrier status [El-Hattab et al 2010].

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutations in the family.

Clinical Description

Natural History

The systemic primary carnitine deficiency (CDSP) phenotype encompasses a broad clinical spectrum including metabolic decompensation in infancy, cardiomyopathy in childhood, fatigability in adulthood, or lack of symptoms. CDSP has been typically associated with infantile metabolic presentation in about half of affected individuals and childhood myopathic presentation in the other half [Roe & Ding 2001, Longo et al 2006]. However, adults with CDSP have been reported with mild or no symptoms. Such milder phenotypes are expected to be underdiagnosed; therefore, it is difficult to determine the relative prevalence of different phenotypes associated with CDSP.

Infantile metabolic (hepatic) presentation. Affected children can present between age three months and two years with episodes of metabolic decompensation triggered by fasting or common illnesses such as upper respiratory tract infection or gastroenteritis. These episodes are characterized clinically by poor feeding, irritability, lethargy, and hepatomegaly. Laboratory evaluations usually reveal hypoketotic hypoglycemia (hypoglycemia with minimal or no ketones in urine), hyperammonemia, and elevated liver transaminases. If affected children are not treated with intravenous dextrose infusion during episodes of metabolic decompensation (see Management), they may develop coma and die [Roe & Ding 2001, Stanley 2004, Longo et al 2006].

Childhood myopathic (cardiac) presentation. The average age of myopathic presentation is between age two and four years, indicating that the myopathic manifestations of CDSP may develop over a longer period of time. Myopathic manifestations include dilated cardiomyopathy, hypotonia, skeletal muscle weakness, and elevated serum creatine kinase (CK). Death from cardiac failure can occur before the diagnosis is established, indicating that this presentation can be fatal if not treated. Older children with the infantile presentation may also develop myopathic manifestations including elevated CK, cardiomyopathy, and skeletal muscle weakness [Roe & Ding 2001, Stanley 2004, Longo et al 2006].

Adulthood presentation. Several women have been diagnosed with CDSP after newborn screening identified low carnitine levels in their infants. About half of those women complained of fatigability, whereas the other half were asymptomatic. One woman was found to have dilated cardiomyopathy and another had arrhythmias [Vijay et al 2006, Schimmenti et al 2007, El-Hattab et al 2010, Lee et al 2010]. An asymptomatic adult male with CDSP has also been reported [Spiekerkoetter et al 2003].

Pregnancy-related symptoms. Pregnancy is a metabolically challenging state because energy consumption significantly increases. In addition, during pregnancy the plasma carnitine levels are physiologically lower than those of non-pregnant controls [Schoderbeck et al 1995]. Affected women can have decreased stamina or worsening of cardiac arrhythmia during pregnancy, suggesting that CDSP may manifest or exacerbate during pregnancy [Schimmenti et al 2007, El-Hattab et al 2010].

Atypical manifestations. Other manifestations reported in individuals with CDSP include:

Heterozygous carriers. Heterozygous carriers are asymptomatic. Although it was speculated that benign left ventricular hypertrophy could be associated with a heterozygous pathogenic SLC22A5 allele in middle-aged adults [Koizumi et al 1999], a more recent study by Amat di San Filippo et al [2008] revealed that heterozygosity for mutations in this gene is not associated with cardiomyopathy.

Prognosis. Infantile metabolic and childhood myopathic presentations of CDSP can be fatal if untreated (see Management). The long-term prognosis is favorable as long as affected individuals remain on carnitine supplements. Repeated attacks of hypoglycemia or sudden death from arrhythmia have been described in affected individuals discontinuing carnitine supplementation [Roe & Ding 2001, Cederbaum et al 2002, Stanley 2004, Longo et al 2006].

Pathophysiology

Carnitine deficiency results in defective fatty acid oxidation. When fat cannot be utilized glucose is consumed without regeneration via gluconeogenesis resulting in hypoglycemia. In addition, fats released from adipose tissue accumulate in the liver, skeletal muscle, and heart, resulting in hepatic steatosis and myopathy [Longo et al 2006].

Genotype-Phenotype Correlations

Fibroblast carnitine transport is reduced in all affected individuals. However, it has been demonstrated that carnitine transport is higher in the fibroblasts of asymptomatic individuals than in the fibroblasts of symptomatic individuals. Nonsense and frameshift mutations are typically associated with lower carnitine transport and are more prevalent in symptomatic individuals whereas missense mutations and inframe deletions may result in protein with retained residual carnitine transport activity and are more prevalent in asymptomatic individuals [Rose et al 2012].

Prevalence

CDSP has a frequency of 1:40,000 in Japan [Koizumi et al 1999] and 1:120,000 in Australia [Wilcken et al 2003]. The disease is very frequent in the Faroe Islands with an estimated carrier frequency of 1:20 [Lund et al 2007].

The frequency in the US and Europe has not been defined, but from newborn screening data and reported cases the prevalence in the US can be estimated to be approximately 1:50,000.

  • Missouri. Screening of approximately 155,000 newborns in 2009 and 2010 identified seven affected newborns, giving an incidence of approximately 1:22,000 [Personal communication, Missouri State Newborn Screening Laboratory].
  • Texas. Screening of approximately 850,000 newborns from 2008 to 2010 identified 12 affected newborns, giving an incidence of approximately 1:70,000 [Personal communication, Texas Department of State Health Services].
  • California. Screening of approximately 3,413,000 newborns from July 2005 to November 2011 identified 48 affected newborns, giving an incidence of approximately 1:70,000 [Personal communication, Newborn Screening Program of the California Department of Public Health].

Differential Diagnosis

Systemic primary carnitine deficiency (CDSP) needs to be differentiated from secondary carnitine deficiency seen in the following situations [Flanagan et al 2010]:

Note to clinicians: For a patient-specific ‘simultaneous consult’ related to this disorder, go to Image SimulConsult.jpg an interactive diagnostic decision support software tool that provides differential diagnoses based on patient findings (registration or institutional access required).

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with systemic primary carnitine deficiency (CDSP), the following evaluations are recommended:

  • Echocardiogram and electrocardiogram
  • Serum creatine kinase (CK) concentration
  • Liver transaminases
  • Pre-prandial blood glucose concentration
  • Medical genetics consultation

Treatment of Manifestations

L-carnitine supplementation. The main treatment for CDSP is oral levocarnitine (L-carnitine) supplementation. Typically a high dose, 100-400 mg/kg/day, divided in three doses is required. Individuals with CDSP respond well if oral L-carnitine supplementation is started before irreversible organ damage occurs. Metabolic decompensation and skeletal and cardiac muscle functions improve with L-carnitine supplementations.

Oral L-carnitine supplementation in infants with CDSP identified through newborn screening results in slow normalization of the plasma carnitine concentration. The carnitine dose needs to be adjusted according to the plasma carnitine concentrations, which should be measured frequently.

L-carnitine supplementation has relatively few side effects:

  • High doses of oral L-carnitine can cause increased gastrointestinal motility, diarrhea, and intestinal discomfort.
  • Oral L-carnitine can be metabolized by intestinal bacteria to produce trimethylamine that has a fishy odor. Oral metronidazole at a dose of 10 mg/kg/day for 7-10 days and/or decreasing the carnitine dose usually results in the resolution of the odor [Longo et al 2006].

Note:

(1) An unaffected infant born to a mother with CDSP can have low carnitine levels detected on newborn screening; in these infants oral L-carnitine supplementation is followed by a rise in plasma carnitine concentration within days or a few weeks [Stanley 2004, Schimmenti et al 2007, El-Hattab et al 2010].

(2) Asymptomatic adults with CDSP have been reported; however, the limited literature and the lack of follow-up make it unclear whether these individuals have potential health risks. Because some fatty acid oxidation defects such as medium chain acyl CoA dehydrogenase (MCAD) deficiency can remain asymptomatic until it results in sudden death or another acute presentation during stress [Ruitenbeek et al 1995, Feillet et al 2003], it is prudent to treat asymptomatic individuals with CDSP with L-carnitine supplementation to prevent the possibility of decompensation during intercurrent illness or stress [El-Hattab et al 2010].

Other

  • Hypoglycemic episodes are treated with intravenous dextrose infusion.
  • Cardiomyopathy requires management by specialists in cardiology.

Prevention of Primary Manifestations

Maintaining appropriate plasma carnitine concentrations through oral L-carnitine supplementation (See Treatment of Manifestations) and preventing hypoglycemia (with frequent feeding and avoiding fasting) typically eliminate the risk of metabolic, hepatic, cardiac, and muscular complications.

Note: Hospitalization to administer intravenous glucose is recommended for individuals with CDSP who are required to fast because of medical or surgical procedures or who cannot tolerate oral intake because of an illness such as gastroenteritis.

Surveillance

No clinical guidelines for surveillance are available.

The following evaluations are suggested:

  • Echocardiogram and electrocardiogram. Perform annually during childhood and less frequently in adulthood. Individuals with cardiomyopathy require management and follow up by specialists in cardiology.
  • Plasma carnitine concentration. Monitor frequently until levels reach the normal range, thereafter, measure three times a year during infancy and early childhood, twice a year in older children, and annually in adults.
  • Serum CK concentration and liver transaminases. Consider measuring during acute illnesses.

Agents/Circumstances to Avoid

Individuals with CDSP should avoid fasting longer than age-appropriate periods.

Evaluation of Relatives at Risk

Sibs of affected individuals should be tested by measuring plasma carnitine concentrations. If the carnitine levels are low, further evaluation for CDSP is needed by either fibroblast carnitine transport assay or molecular genetic testing if the disease-causing mutations have been identified in the family.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Pregnancy is a metabolically challenging state because energy consumption significantly increases. In addition, plasma carnitine levels are physiologically lower during pregnancy than those of non-pregnant controls [Schoderbeck et al 1995]. Affected women can have decreased stamina or worsening of cardiac arrhythmia during pregnancy, suggesting that CDSP may manifest or exacerbate during pregnancy [Schimmenti et al 2007, El-Hattab et al 2010]. Therefore, all pregnant women with CDSP, including those who are asymptomatic, require close monitoring of plasma carnitine levels and increased carnitine supplementation as needed to maintain normal plasma carnitine levels.

Therapies Under Investigation

Search Clinical Trials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Systemic primary carnitine deficiency (CDSP) is inherited in an autosomal recessive manner.

Risk to Family Members

Parents of a proband

  • The parents of an affected child are obligate heterozygotes (i.e., carriers of one mutant allele).
  • Heterozygotes (carriers) are asymptomatic.

Sibs of a proband

  • At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
  • Once an at-risk sib is known to be unaffected, the risk of his/her being a carrier is 2/3.
  • Heterozygotes (carriers) are asymptomatic.

Offspring of a proband

  • The offspring of an individual with systemic primary carnitine deficiency are obligate heterozygotes (carriers) for a disease-causing mutation in SLC22A5.
  • Unless an individual with systemic primary carnitine deficiency has children with an affected individual or a carrier, his/her offspring will be obligate heterozygotes (carriers) for a disease-causing mutation in SLC22A5.

Other family members. Each sib of the proband’s parents is at a 50% risk of being a carrier.

Carrier Detection

Molecular Genetic testing. Carrier testing for at-risk family members is possible if the disease-causing mutations in the family have been identified.

Biochemical testing. Heterozygous carriers usually have about 50% carnitine transport activity in fibroblasts and can have borderline low plasma carnitine levels [Scaglia et al 1998]. Plasma carnitine levels are not a reliable indicator for heterozygous carrier status; thus, either molecular testing or fibroblast carnitine transport assay is needed to determine carrier status [El-Hattab et al 2010] (see Testing, Heterozygous carriers).

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

  • The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected, are carriers, or are at risk of being carriers.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

Prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at approximately 15 to 18 weeks’ gestation or chorionic villus sampling (CVS) at approximately ten to 12 weeks’ gestation. The disease-causing mutations in the family must be identified before prenatal testing can be performed.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Requests for prenatal testing for conditions which (like systemic primary carnitine deficiency) do not affect intellect and have some treatment available are not common. Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although decisions about prenatal testing are the choice of the parents, discussion of these issues is appropriate.

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the disease-causing mutations have been identified.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • National Library of Medicine Genetics Home Reference
  • Children Living with Inherited Metabolic Diseases (CLIMB)
    Climb Building
    176 Nantwich Road
    Crewe CW2 6BG
    United Kingdom
    Phone: 0800-652-3181 (toll free); 0845-241-2172
    Fax: 0845-241-2174
    Email: info.svcs@climb.org.uk
  • FOD Family Support Group (Fatty Oxidation Disorder)
    PO Box 54
    Okemos MI 48805-0054
    Phone: 517-381-1940
    Fax: 866-290-5206 (toll-free)
    Email: deb@fodsupport.org; fodgroup@gmail.com

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A. Systemic Primary Carnitine Deficiency: Genes and Databases

Data are compiled from the following standard references: gene symbol from HGNC; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B. OMIM Entries for Systemic Primary Carnitine Deficiency (View All in OMIM)

212140CARNITINE DEFICIENCY, SYSTEMIC PRIMARY; CDSP
603377SOLUTE CARRIER FAMILY 22 (ORGANIC CATION TRANSPORTER), MEMBER 5; SLC22A5

Molecular Genetic Pathogenesis

Carnitine is required for the transfer of long-chain fatty acids from the cytoplasm to the mitochondrial matrix for beta-oxidation. During periods of fasting, fatty acids are the predominant substrate for energy production via oxidation in the liver, cardiac muscle, and skeletal muscle. Carnitine is transported inside the cells by an organic cation transporter (OCTN2) present in the heart, muscle, and kidney. OCTN2 is the protein product of SLC22A5. CDSP is a disorder of the carnitine cycle caused by the lack of functional OCTN2 resulting in urinary carnitine wasting, low plasma carnitine levels, and decreased intracellular carnitine accumulation.

Normal allelic variants. SLC22A5 comprises ten exons spanning approximately 3.2 kb.

Pathologic allelic variants. More than 100 mutations have been reported in the Human Gene Mutation Database (HGMD) (see Table A) and the SLC22A5 Database at the ARUP Laboratories (see Table A).

About half of these mutations are missense mutations. Nonsense mutations, splice site mutations, insertions, and small deletions comprise the remaining half of reported mutations.

One large deletion encompassing the entire SLC22A5 has been reported [Li et al 2010].

Normal gene product. SLC22A5 encodes the high affinity sodium-dependent carnitine transporter, organic cation transporter 2 (OCTN2). OCTN2 is a transmembrane protein that comprises 557 amino acids; it includes 12 transmembrane domains and one ATP binding domain.

Abnormal gene product. SLC22A5 mutations result in dysfunctional OCTN2 and decreased carnitine transport in various tissues.

References

Medical Genetic Searches: A specialized PubMed search designed for clinicians that is located on the PubMed Clinical Queries page .Image PubMed.jpg

Literature Cited

  1. Amat di San Filippo C, Taylor MR, Mestroni L, Botto LD, Longo N. Cardiomyopathy and carnitine deficiency. Mol Genet Metab. 2008;94:162–6. [PMC free article: PMC2430214] [PubMed: 18337137]
  2. Cano A, Ovaert C, Vianey-Saban C, Chabrol B. Carnitine membrane transporter deficiency: a rare treatable cause of cardiomyopathy and anemia. Pediatr Cardiol. 2008;29:163–5. [PubMed: 17926086]
  3. Cederbaum SD, Koo-McCoy S, Tein I, Hsu BY, Ganguly A, Vilain E, Dipple K, Cvitanovic-Sojat L, Stanley C. Carnitine membrane transporter deficiency: a long-term follow up and OCTN2 mutation in the first documented case of primary carnitine deficiency. Mol Genet Metab. 2002;77:195–201. [PubMed: 12409266]
  4. El-Hattab AW, Li FY, Shen J, Powell BR, Bawle EV, Adams DJ, Wahl E, Kobori JA, Graham B, Scaglia F, Wong LJ. Maternal systemic primary carnitine deficiency uncovered by newborn screening: clinical, biochemical, and molecular aspects. Genet Med. 2010;12:19–24. [PubMed: 20027113]
  5. Erguven M, Yilmaz O, Koc S, Caki S, Ayhan Y, Donmez M, Dolunay G. A case of early diagnosed carnitine deficiency presenting with respiratory symptoms. Ann Nutr Metab. 2007;51:331–4. [PubMed: 17726310]
  6. Feillet F, Steinmann G, Vianey-Saban C, de Chillou C, Sadoul N, Lefebvre E, Vidailhet M, Bollaert PE. Adult presentation of MCAD deficiency revealed by coma and severe arrythmias. Intensive Care Med. 2003;29:1594–7. [PubMed: 12897989]
  7. Flanagan JL, Simmons PA, Vehige J, Willcox MD, Garrett Q. Role of carnitine in disease. Nutr Metab (Lond). 2010;7:30. [PMC free article: PMC2861661] [PubMed: 20398344]
  8. Koizumi A, Nozaki J, Ohura T, Kayo T, Wada Y, Nezu J, Ohashi R, Tamai I, Shoji Y, Takada G, Kibira S, Matsuishi T, Tsuji A. Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency. Hum Mol Genet. 1999;8:2247–54. [PubMed: 10545605]
  9. Lee NC, Tang NL, Chien YH, Chen CA, Lin SJ, Chiu PC, Huang AC, Hwu WL. Diagnoses of newborns and mothers with carnitine uptake defects through newborn screening. Mol Genet Metab. 2010;100:46–50. [PubMed: 20074989]
  10. Li FY, El-Hattab AW, Bawle EV, Boles RG, Schmitt ES, Scaglia F, Wong LJ. Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency. Hum Mutat. 2010;31:E1632–51. [PubMed: 20574985]
  11. Longo N, Amat di San Filippo N, Pasquali M. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet. 2006;142C:77–85. [PMC free article: PMC2557099] [PubMed: 16602102]
  12. Lund AM, Joensen F, Hougaard DM, Jensen LK, Christensen E, Christensen M, Nørgaard-Petersen B, Schwartz M, Skovby F. Carnitine transporter and holocarboxylase synthetase deficiencies in The Faroe Islands. J Inherit Metab Dis. 2007;30:341–9. [PubMed: 17417720]
  13. Roe CR, Ding J. Mitochondrial fatty acid oxidation disorders. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic Bases of Inherited Disease. 8 ed. New York, NY: McGraw-Hill; 2001:2297-326.
  14. Rose EC, di San Filippo CA, Ndukwe Erlingsson UC, Ardon O, Pasquali M, Longo N. Genotype-phenotype correlation in primary carnitine deficiency. Hum Mutat. 2012;33:118–23. [PMC free article: PMC3240685] [PubMed: 21922592]
  15. Ruitenbeek W, Poels PJ, Turnbull DM, Garavaglia B, Chalmers RA, Taylor RW, Gabreëls FJ. Rhabdomyolysis and acute encephalopathy in late onset medium chain acyl-CoA dehydrogenase deficiency. J Neurol Neurosurg Psychiatry. 1995;58:209–14. [PMC free article: PMC1073319] [PubMed: 7876853]
  16. Scaglia F, Longo N. Primary and secondary alterations of neonatal carnitine metabolism. Semin Perinatol. 1999;23:152–61. [PubMed: 10331466]
  17. Scaglia F, Wang Y, Longo N. Functional characterization of the carnitine transporter defective in primary carnitine deficiency. Arch Biochem Biophys. 1999;364:99–106. [PubMed: 10087170]
  18. Scaglia F, Wang Y, Singh RH, Dembure PP, Pasquali M, Fernhoff PM, Longo N. Defective urinary carnitine transport in heterozygotes for primary carnitine deficiency. Genet Med. 1998;1:34–39. [PubMed: 11261427]
  19. Schimmenti LA, Crombez EA, Schwahn BC. Expanded newborn screening identifies maternal primary carnitine deficiency. Mol Genet Metab. 2007;90:441–5. [PubMed: 17126586]
  20. Schoderbeck M, Auer B, Legenstein E, Genger H, Sevelda P, Salzer H, Marz R, Lohninger A. Pregnancy-related changes of carnitine and acylcarnitine concentrations of plasma and erythrocytes. J Perinat Med. 1995;23:477–85. [PubMed: 8904477]
  21. Spiekerkoetter U, Huener G, Baykal T, Demirkol M, Duran M, Wanders R, Nezu J, Mayatepek E. Silent and symptomatic primary carnitine deficiency within the same family due to identical mutations in the organic cation/carnitine transporter OCTN2. J Inherit Metab Dis. 2003;26:613–5. [PubMed: 14605509]
  22. Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad Sci. 2004;1033:42–51. [PubMed: 15591002]
  23. Vijay S, Patterson A, Olpin S, Henderson MJ, Clark S, Day C, Savill G, Walter JH. Carnitine transporter defect: diagnosis in asymptomatic adult women following analysis of acylcarnitines in their newborn infants. J Inherit Metab Dis. 2006;29:627–30. [PubMed: 16865412]
  24. Wang Y, Korman SH, Ye J, Gargus JJ, Gutman A, Taroni F, Garavaglia B, Longo N. Phenotype and genotype variation in primary carnitine deficiency. Genet Med. 2001;3:387–392. [PubMed: 11715001]
  25. Wilcken B, Wiley V, Hammond J, Carpenter K. Screening newborns for inborn errors of metabolism by tandem mass spectrometry. N Engl J Med. 2003;348:2304–12. [PubMed: 12788994]
  26. Wilcken B, Wiley V, Sim KG, Carpenter K. Carnitine transporter defect diagnosed by newborn screening with electrospray tandem mass spectrometry. J Pediatr. 2001;138:581–4. [PubMed: 11295726]

Chapter Notes

Revision History

  • 15 March 2012 (me) Review posted live
  • 5 December 2011 (aeh) Original submission
Copyright © 1993-2014, University of Washington, Seattle. All rights reserved.

For more information, see the GeneReviews Copyright Notice and Usage Disclaimer.

For questions regarding permissions: ude.wu@tssamda.

Bookshelf ID: NBK84551PMID: 22420015
PubReader format: click here to try

Views

Tests in GTR by Gene

Tests in GTR by Condition

Related information

  • OMIM
    Related OMIM records
  • PMC
    PubMed Central citations
  • PubMed
    Links to pubmed
  • Gene
    Gene records cited in chapters on the NCBI bookshelf. Links are provided by the authors or the NCBI Bookshelf staff.

Related citations in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...