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Primary carnitine deficiency
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Primary Carnitine Deficiency

Primary carnitine deficiency blocks the body’s ability to use fats for energy, leading to severe metabolic crises and a risk of sudden death.

Overview

Primary carnitine deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Carnitine, a natural substance acquired mostly through food, is used by cells to process fats and produce energy.

Symptoms

Signs and symptoms typically appear during infancy or early childhood and can include:

  • Severe brain dysfunction (encephalopathy)
  • Weakening and enlargement of the heart (cardiomyopathy)
  • Vomiting
  • Muscle weakness
  • Low blood glucose (hypoglycemia)
  • Potential sudden death (risk present in all affected individuals)

Severity varies; some individuals remain asymptomatic.

Episodes are often triggered by fasting or illnesses such as viral infections and may be mistaken for Reye syndrome.

Frequency

Primary carnitine deficiency occurs in approximately 1 in 100,000 newborns worldwide. In Japan, the prevalence is about 1 in 40,000 newborns.

Causes

Variants (mutations) in the SLC22A5 gene cause primary carnitine deficiency. This gene provides instructions for making the protein OCTN2, which transports carnitine into cells. Cells need carnitine to bring certain fatty acids into mitochondria, the energy‑producing centers of the cell. Fatty acids are a major energy source for the heart and muscles, especially during fasting.

When SLC22A5 variants produce an absent or dysfunctional OCTN2 protein, intracellular carnitine levels drop. Without carnitine, fatty acids cannot enter mitochondria, leading to reduced energy production, muscle weakness, hypoglycemia, and accumulation of fatty acids that damage the liver, heart, and muscles.

Learn more about the gene associated with Primary carnitine deficiency

  • SLC22A5

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have a variant to cause the disorder. Parents of an affected individual each carry one copy of the altered gene but typically do not show signs or symptoms.

Other Names

  • Carnitine transporter deficiency
  • Carnitine uptake defect
  • Carnitine uptake deficiency
  • CUD
  • Renal carnitine transport defect
  • Systemic carnitine deficiency

Additional Information & Resources

Genetic Testing Information

  • Genetic Testing Registry: Renal carnitine transport defect

Genetic and Rare Diseases Information Center

  • Systemic primary carnitine deficiency

Patient Support and Advocacy Resources

  • National Organization for Rare Disorders (NORD)

Clinical Trials

  • ClinicalTrials.gov

Catalog of Genes and Diseases from OMIM

  • CARNITINE DEFICIENCY, SYSTEMIC PRIMARY; CDSP

Scientific Articles on PubMed

  • PubMed

References

  • Amat di San Filippo C, Pasquali M, Longo N. Pharmacological rescue of carnitine transport in primary carnitine deficiency. Hum Mutat. 2006 Jun;27(6):513-23. doi: 10.1002/humu.20314.
  • 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 Jan;12(1):19-24. doi: 10.1097/GIM.0b013e3181c5e6f7.
  • Lahjouji K, Mitchell GA, Qureshi IA. Carnitine transport by organic cation transporters and systemic carnitine deficiency. Mol Genet Metab. 2001 Aug;73(4):287-97. doi: 10.1006/mgme.2001.3207.
  • Lamhonwah AM, Olpin SE, Pollitt RJ, Vianey-Saban C, Divry P, Guffon N, Besley GT, Onizuka R, De Meirleir LJ, Cvitanovic-Sojat L, Baric I, Dionisi-Vici C, Fumic K, Maradin M, Tein I. Novel OCTN2 mutations: no genotype-phenotype correlations: early carnitine therapy prevents cardiomyopathy. Am J Med Genet. 2002 Aug 15;111(3):271-84. doi: 10.1002/ajmg.10585.
  • 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 Aug;31(8):E1632-51. doi: 10.1002/humu.21311.
  • Longo N, Amat di San Filippo C, Pasquali M. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet. 2006 May 15;142C(2):77-85. doi: 10.1002/ajmg.c.30087.
  • Magoulas PL, El-Hattab AW. Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management. Orphanet J Rare Dis. 2012 Sep 18;7:68. doi: 10.1186/1750-1172-7-68.
  • Schimmenti LA, Crombez EA, Schwahn BC, Heese BA, Wood TC, Schroer RJ, Bentler K, Cederbaum S, Sarafoglou K, McCann M, Rinaldo P, Matern D, di San Filippo CA, Pasquali M, Berry SA, Longo N. Expanded newborn screening identifies maternal primary carnitine deficiency. Mol Genet Metab. 2007 Apr;90(4):441-5. doi: 10.1016/j.ymgme.2006.10.003.
  • Shibbani K, Fahed AC, Al-Shaar L, Arabi M, Nemer G, Bitar F, Majdalani M. Primary carnitine deficiency: novel mutations and insights into the cardiac phenotype. Clin Genet. 2014 Feb;85(2):127-37. doi: 10.1111/cge.12112.
  • Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad Sci. 2004 Nov;1033:42-51. doi: 10.1196/annals.1320.004.
  • Tein I. Carnitine transport: pathophysiology and metabolism of known molecular defects. J Inherit Metab Dis. 2003;26(2-3):147-69. doi: 10.1023/a:1024481016187.
  • 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 Nov-Dec;3(6):387-92. doi: 10.1097/00125817-200111000-00002.

Frequently Asked Questions

Parents and caregivers should watch for sudden lethargy, unexplained vomiting, and extreme muscle weakness, particularly after a period of fasting or during a viral illness. These episodes often mimic Reye syndrome and may be accompanied by low blood sugar (hypoglycemia) or confusion. If a child becomes unusually sleepy, difficult to wake, or shows signs of respiratory distress, it is a medical emergency requiring immediate hospital evaluation to prevent severe brain dysfunction or cardiac arrest.
Unlike many other metabolic disorders that require strict fat restriction, primary carnitine deficiency is managed primarily through high-dose oral L-carnitine supplementation rather than by eliminating fats from the diet. However, avoiding prolonged fasting is critical. Patients are often advised to consume complex carbohydrates and avoid skipping meals, especially during illnesses. During acute metabolic crises, intravenous glucose and carnitine are administered to stabilize blood sugar levels and provide an alternative energy source while the body recovers.
Yes, primary carnitine deficiency is often detected through newborn screening programs that measure acylcarnitine profiles in a blood spot sample. A low total carnitine level in a newborn is a key indicator. If the initial screen is abnormal, confirmatory testing via plasma acylcarnitine analysis and urine organic acids is performed. Early detection through these non-invasive blood tests allows for the initiation of carnitine therapy before any permanent damage to the heart or brain occurs.
Primary carnitine deficiency is inherited in an autosomal recessive pattern, meaning a child must inherit two defective copies of the SLC22A5 gene, one from each parent, to develop the condition. Parents are typically asymptomatic carriers. If a child is diagnosed, genetic testing can confirm the specific mutations, and siblings can be tested for carrier status or the condition itself. Genetic counseling is recommended for families to understand the 25% recurrence risk in future pregnancies and to discuss options such as prenatal or preimplantation genetic diagnosis.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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