Analysis of primary carnitine deficiency with sudden death in two pedigrees

Objective Primary carnitine deficiency(PCD)is an autosomal recessive disorder of fatty acid oxidation due to mutations in SLC22A5 gene, which encodes organic cation transporter 2(OCTN2). Defects of the OCTN2 prevent tissues from accumulating carnitine, resulting in renal carnitine wasting and low plasma carnitine.PCD is a potentially deadly disease.In the present article, we discussed clinical manifestation and gene mutations in two primary carnitine deficiency families, and analyzed the causes of sudden death in three cases. Methods We retrospectively analyzed clinical data of two PCD families.Probands from both families received test of serum ammonia, lactic acid, hepatic and myocardial enzymes.The results indicated probability of PCD.Further sequencing of the SLC22A5 gene was performed in diseased children and family members. Results Probands from both families showed a significant decrease in free carnitine and several acyl carnitine.Fever, vomiting, drowsiness and other manifestations were found in three death children before the onset of disease.Proband from the first family had a c. 760C>T(p.R254X) homozygous mutation, other family members were c. 760C>T heterozygous.Proband from the first family died of severe arrhythmia and cardiomyopathy.The autopsy showed broken or wavy arrangement of the part of myocardial fibers and diffused fatty degeneration of hepatocytes, with infiltration of neutrophils in some of the alveolar.Proband from the second family were heterozygous of two mutations: c. 760C>T and c. 844dupC (p.R282fs), inherited from parents.He was asymptomatic when was diagnosed but there had been a slight myocardial hypertrophy and increased blood ammonia.However, the indicators returned to normal following L-carnitine supplementation.Two died cases were suspected "viral myocarditis" in the second family. Conclusion The PCD chil-dren often show no symptom in quiescent stage of the disease.However, the disease can be triggered by common cold or diarrhea, aggravate rapidly and even result in sudden death.Proband from the first family had occurred sudden cardiac death caused by systemic carnitine deficiency.The homozygous c. 760C> T mutation, and the heterozygous c. 760C> T combined with c. 844dupC mutations might be the pathogenesis basis of family Ⅰ and family Ⅱ, respectively.Early diagnosis and treatment is the key to long-term prognosis. Key words: Primary carnitine deficiency; Cardiomyopathy; Sudden death; Gene