Acylcarnitine is then converted back to carnitine as catalyzed by inner mitochondrial membrane carnitine acyltransferase ii so that, on the one hand, carnitine can recombine with another molecule of acylcoa in the membrane space and the acylcoa produced by carnitine acyltransferase ii can now enter the betaoxidation pathway of fatty acids inside. Tissue carnitine levels low enough to impair mitochondrial fatty acid oxidation 2. It can cause hypoketotic hypoglycemia or cardiomyopathy in children, and sudden death in children and adults. With carnitine deficiency, cells that rely on fatty acids for energy may start to work poorly. Muscle weakness and hypertrophic cardiomyopathy are common manifestations. Carnitine is essential for the transfer of longchain fatty acids from the cytosol into mitochondria for subsequent.
The presentation of patient with spcd can be incredibly varied, from asymptomatic to lethal cardiac manifestations. Understanding primary carnitine deficiency child saint. Vmax for carnitine transport was reduced to 50% of controls value in the parents and one brother. Secondary carnitine deficiency can be caused by a number of organic acidemias, defects of fatty acid oxidation and of the carnitine cycle. Primary carnitine deficiency and newborn screening for. A lack of carnitine results in impaired energy production from longchain fatty acids, especially during periods of fasting or stress. Analysis of clinical and pathological features of a case.
P46s mutation was initially reported in mothers with primary carnitine deficiency identified by expanded newborn screening in the child 8. Primary systemic carnitine deficiency can happen when the protein that is responsible for bringing carnitine into cells undergoes a genetic change. Systemic primary carnitine deficiency is an autosomal recessive disorder caused by the deficiency of carnitine transporter. Primary carnitine deficiency is an autosomal recessive disorder of fatty acid oxidation caused by defective carnitine transport. Primary systemic carnitine deficiency or carnitine uptake defect omim 212140 is a potentially lethal, autosomal recessive disorder characterized by. Signs and symptoms of primary carnitine deficiency typically appear during infancy or. Pdf primary and secondary carnitine deficiency syndromes. However, pcd is the only genetic defect in which carnitine deficiency is the cause. Mothers with primary carnitine deficiency can also be identified by low carnitine levels in their infant by newborn screening. Systemic primary carnitine deficiency is an inherited metabolic disease with variable severity and age at onset. Thus, if carnitine is deficient, this will result in defective fatty acid oxidation. An autosomal recessive inherited disorder caused by mutations in the slc22a5 gene. Carnitine is especially important for certain cells, such as muscle cells. Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the slc22a5 gene that encodes the carnitine.
Primary carnitine deficiency genetic and rare diseases. In the united states, it occurs in approximately 1 in 100,000 newborns. Primary carnitine deficiency is a genetic inherited disorder of the carnitine transporter system. Secondary carnitine deficiency can by caused by a number of health problems. Pdf primary carnitine deficiency and cardiomyopathy. Secondary carnitine deficiency is when there isnt enough carnitine in the blood. During periods of fasting, fatty acids are the predominant source of energy production. Deficiency in octn2 carnitine transporter leads to systemic primary carnitine deficiency cdsp. Carnitine is a nutrient that helps the bodys cells work normally. Signs and symptoms of systemic primary carnitine deficiency are due to the buildup of fatty acids in.
Summary systemic primary carnitine deficiency cdsp is a rare metabolic disorder in which the body cannot properly process fats into energy. Systemic primary carnitine deficiency cdsp is an autosomal recessive disorder of carnitine transportation typically characterized by episodes of hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia in infants. Primary carnitine deficiency pcd is a genetic disorder in which the body is unable to use certain fats as a source of energy when fasting not eating. Primary carnitine deficiency is a rare health problem a child is born with.
The mother and probably the healthy sister had impaired uptake. The sole example of primary carnitine deficiency is the genetic defect involving the active transport across the plasmalemmal membrane. Carnitine deficiency an overview sciencedirect topics. These findings showed that the defect in this form of carnitine deficiency was an inability to establish a concentration gradient across the cell membrane. Uptake of carnitine by cultured fibroblasts was negligible in both patients. Carnitine uptake defect primary carnitine deficiency. It may also be recommended to the patients taking certain drugs such as valproic acid for seizures or. Primary carnitine deficiency and newborn screening for disorders. Not all infants with low free carnitine are affected with spcd. The advances in our understanding of fatty acid oxi. In recent years, with the application of tandem mass spectrometry, an increasing number of patients with primary carnitine deficiency have been diagnosed in china. Systemic primary carnitine deficiency with hypoglycemic. Fibroblasts from affected patients have reduced carnitine.
Review open access systemic primary carnitine deficiency. Primary carnitine deficiency is an autosomal recessive disorder resulting from impaired carnitine transport and primarily affects skeletal and cardiac muscle. This disease presents early in life with hypoketotic hypoglycemia or later in life with skeletal myopathy or cardiomyopathy. Primary systemic carnitine deficiency symptoms, causes, diagnosis, and treatment information for primary systemic carnitine deficiency carnitine transporter deficiency with alternative diagnoses, fulltext book chapters, misdiagnosis, research treatments, prevention, and prognosis. Primary carnitine deficiencies in children charles a. At present, the existing reports have mainly focused on screening and there are no reports.
Vegetarians possess a greater bioavailability than meat eaters. Primary carnitine deficiency pcd is an autosomal recessive disorder of mitochondrial. It is characterized by decreased carnitine accumulation in tissues and increased losses of carnitine in the urine. Primary carnitine deficiency is the bodys inability to use certain fats for energy due to inadequate intake inadequate intake of or inability to metabolize the amino acid carnitine. Systemic primary carnitine deficiency spcd exact prevalence is unknown and varies depending on ethnicity. Carnitine deficiency occurs in aberrations of carnitine. Systemic primary carnitine deficiency integrated genetics. It is also a drug approved by the food and drug administration to treat primary and certain secondary carnitine deficiency syndromes. Fibroblasts from affected patients have reduced carnitine transport. Mutations in the organic cationcarnitine transporter. Affected infants show low levels of free carnitine and all other acylcarnitine species by tandem mass spectrometry.
Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. The kd is absolutely contraindicated in primary carnitine deficiency, carnitine palmitoyltransferase i or ii deficiency, carnitine translocase deficiency. If you have problems viewing pdf files, download the latest version of adobe reader. Primary or secondary carnitine deficiency is present in all these clinical conditions except carnitine palmitoyltransferase type i and the classic adult form of carnitine palmitoyltransferase type ii deficiency. Enable javascript to view the expandcollapse boxes. Systemic primary carnitine deficiency is an autosomal recessive disorder of the carnitine cycle caused by mutations in the slc22a5 gene that encodes the carnitine transporter, organic cation. Newborn screening programmes for primary carnitine deficiency can identify affected patients at risk for this condition.
Pdf abstract systemic primary carnitine deficiency cdsp is an autosomal recessive disorder of carnitine transportation. Primary carnitine deficiency also known as carnitine uptake defect, carnitine transported defect or systemic carnitine deficiency is an autosomal recessive disorder of the carnitine cycle that. Neonatal screening for primary carnitine deficiency mdpi. Secondary carnitine deficiencies may be hereditary or acquired. Primary carnitine deficiency is an autosomal recessive metabolic disorder caused by a deficiency in the carnitine transporters. The initial signs and symptoms of this disorder occur during infancy or early childhood and often include brain function abnormalities, cardiomyopathy, confusion, vomiting, muscle weakness, and hypoglycemia. Carnitine is released in the mitochondrial matrix and then return to the cytoplasm for another cycle, while the fatty acids are conjugated back to coenzyme a in the mitochondrial matrix and then enter the pathway of. A carnitine uptake defect cud or primary carnitine transporter deficiency is a rare fatty acid oxidation disorder faod. Primary carnitine deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food fasting. Carnitine is required for the transfer of longchain fatty acids from the cytoplasm into the mitochondria for beta oxidation 5. Two boys from different families had primary carnitine deficiency. Carnitine is used in the treatment of primary and secondary carnitine deficiency 30. The lack of the plasma membrane carnitine transporter octn2 results in urinary.
Primary carnitine deficiency is caused by a defect in the plasma membrane carnitine transporter in kidney and muscle. Primary carnitine deficiency affects males and females in equal numbers, 2 and strikes an estimated one in every 50,000 to one in every 100,000 newborns in the united states. Primary carnitine deficiency this condition is grouped with the defects known as fatty acid oxidation disorders. Main features are cardiomyopathy, myopathy and hypoglycemic encephalopathy. Primary carnitine deficiency is when not enough carnitine can get into cells in the body. Carnitine is often promoted as an aid for weight loss, to improve exercise performance, and to enhance a sense of wellbeing. Primary carnitine deficiency is caused by a defect in the octn2 carnitine transporter encoded by the slc22a5 gene. Fat or adipose tissue is the main energy store of our bodies derived not only from the fat that we eat but also made in the body from any excess calories obtained from our food and drink.
First case report of primary carnitine deficiency manifested. Primary and secondary carnitine deficiency syndromes. The nature and severity of signs and symptoms may vary, but they most often appear during infancy or early childhood and can include severe brain dysfunction encephalopathy, cardiomyopathy, confusion, vomiting, muscle weakness, and hypoglycemia. The nature and severity of signs and symptoms may vary, but they most often appear during infancy or early childhood and can include severe brain dysfunction encephalopathy, cardiomyopathy. Primary carnitine deficiency is an inherited metabolic disorder that impairs the bodys uptake of carnitine, a molecule. Functional and molecular studies in primary carnitine. The ketogenic diet kd is an effective nonpharmacological treatment used as an alternative not only for children but also for adults in the management of refractory epilepsy.
Cdsp to ensure longterm funding for the omim project, we have diversified our revenue stream. Primary carnitine deficiency genetics home reference nih. Carnitine functions to carry fatty acids obtained through diet to the energy centers in muscle cells mitochondria. Primary carnitine deficiency is a genetic condition that prevents the body from using certain fats for energy, particularly during periods without food fasting. Common symptoms reported by people with primary carnitine deficiency. Carnitine deficiency can happen in men, women, and children of all ages and all ethnicities. In japan, this disorder is much more common affecting 1 in every 40,000 newborns. Individuals with pcd are unable to make a specific protein called solute carrier family 22 member 5, which is used to transport a substance called carnitine in and out of cells. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. A deficiency of carnitine results in accumulation of fats in the liver, muscle, and heart. Some may have carnitine deficiency secondary to another metabolic condition or due to maternal carnitine deficiency. Systemic primary carnitine deficiency pcd is a genetic disorder caused by decreased or absent organic cation transporter type 2. The most frequently occurring mutation in this cohort was the c.
Early cases were reported with liver dysfunction, muscular findings weakness and underdevelopment, hypoketotic hypoglycemia, cardiomegaly, cardiomyopathy and marked carnitine deficiency in plasma and tissues, combined with increased excretion in. This is a rare condition caused by an abnormal gene. For language access assistance, contact the ncats public information officer. Systemic primary carnitine deficiency nord national. Because it is mainly concentrated in cities with good conditions, there are few reports of this disease in china. Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Patients with carnitine deficiency may present with hypoketotic hypoglycemia and other symptoms. Patients may also present with an acute illness or have recurring episodes of illness which can include. P46s mutation which was identified in about 15% of the mutant alleles 9. Genetic and rare diseases information center gard po box 8126, gaithersburg, md 208988126 tollfree.
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