TY - CHAP M1 - Book, Section TI - Primary Carnitine Deficiency A1 - Longo, Nicola A1 - Pasquali, Marzia A2 - Murray, Michael F. A2 - Babyatsky, Mark W. A2 - Giovanni, Monica A. A2 - Alkuraya, Fowzan S. A2 - Stewart, Douglas R. Y1 - 2014 N1 - T2 - Clinical Genomics: Practical Applications in Adult Patient Care AB - Disease summary:Primary carnitine deficiency (OMIM 212140) is a disorder of the carnitine cycle that impairs fatty acid oxidation. It is caused by mutations in the SLC22A5 gene encoding the OCTN2 carnitine transporter. Primary carnitine deficiency has a frequency of about 1:40,000, with 1% of the population being carrier for this condition. It has a very high frequency in the Faroe Islands (prevalence 1:1300 people, incidence 1:720) due to a founder effect.The lack of the plasma membrane carnitine transporter results in urinary carnitine wasting, low serum carnitine levels (0-5 μM, normal 25-50 μM), and decreased intracellular carnitine accumulation. Affected patients can have a predominant metabolic (hypoglycemia, hepatic encephalopathy) or cardiac (cardiomyopathy, arrhythmia) presentation. Some people remain asymptomatic for long time, but are at risk for sudden cardiac death.Hereditary basis:Primary carnitine deficiency is transmitted as an autosomal recessive disorder caused by mutations in the SLC22A5 gene on 5q31.1. Penetrance in affected individuals is thought to be very high, although quite a few people are identified as adults due to expanded newborn screening.Differential diagnosis:Primary carnitine deficiency needs to be differentiated from secondary carnitine deficiency. This can occur in disorders of the carnitine cycle (carnitine-acylcarnitine translocase [CACT] or carnitine palmitoyl transferase 2 [CPT-2] deficiency) and fatty acid oxidation (MCAD, VLCAD, LCHAD, TFP deficiency), organic acidemias (propionic, methylmalonic, isovaleric, and glutaric acidemia, 3-methylcrotonylglycinuria, multiple carboxylase deficiency, and other more rare), renal disease (renal Fanconi syndrome, chronic renal failure, dialysis), lysinuric protein intolerance (LPI), chronic ketosis or ketogenic diet, extreme prematurity, prolonged use of intravenous nutrition not supplemented by carnitine, and drug therapy (valproic acid, phenobarbital, phenytoin, carbamazepine, drugs containing pivalic acid). SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102703505 ER -