Carnitine-acylcarnitine translocase deficiency with homozygous mutation of c.199-10T>G: a case report and literature review

Objective To investigate the clinical features of carnitine-acylcarnitine translocase deficiency (CACTD) with c.199-10T>G homozygous mutation and the characteristics of SLC25A20 gene mutation. Methods This study retrospectively analyzed the clinical data, biochemical and genetic features, treatment and outcome of a boy with CACTD with c.199-10T>G homozygous mutation, who admitted to Guangzhou Women and Children's Medical Center in September 2017. Pertinent articles were retrieved from China National Knowledge Infrastructure (CNKI), Wanfang Database, National Center for Biotechnology Information and PubMed from the establishment of these databases to April 2018 using key words including CACT, SLC25A20 and carnitine-acylcarnitine translocase. Clinical information of all affected cases in the retrieved publications was analyzed. Results (1) The full-term boy born vaginally at a local hospital was transferred to neonatal intensive care unit (NICU) of Guangzhou Women and Children's Medical Center at 2 days and 5 hours due to groaning, cyanosis and severe hypoglycemia (0.8 mmol/L) at 15 h after birth. His elder brother with similar symptoms died of unknown reason at 50 days of age. In this case, ammonemia, liver enzyme and creatine kinase were significantly elevated, amino acid analysis suggested liver damage, and high amounts of dicarboxylic aciduria, low free carnitine, markedly increased long-chain acylcarnitine and hypoketotic hypoglycemia were also observed. His electrocardiogram showed atrioventricular block and ventricular tachycardia. After a series of treatments, including repeated electrical cardioversion, lidocaine and amiodarone for arrhythmia, arginine for blood ammonia level reduction, formula supplement containing L-carnitine and medium-chain fatty acid, the patient whose conditions had significantly improved and was discharged at the request of his parents at 29 days old. Two weeks later, he was re-admitted due to diarrhea, and discharged two days later when he was 45 days old. He was lost to follow up since then. (2) A homozygous mutation of c.199-10T>G was detected in this boy in SLC25A20 gene, which was also carried by his parents. (3) Thirty-two publications in English were retrieved, involving 50 cases of CACTD and 100 sequenced alleles. A total of 40 mutations in SLC25A20 gene were found so far, and c.199-10T>G was the most common mutation with a frequency of 22/100. It was identified in 13 patients, including nine homozygous mutations and four compound heterozygous mutations. Symptoms presented within 72 h after birth (25 min-52 h) in all the 13 infants, such as hypoketotic hypoglycemia, hyperammonemia, elevated liver enzyme and creatine kinase, significantly decreased free carnitine level, markedly increased level of long-chain acylcarnitine, dicarboxylic aciduria, arrhythmia and cardiomyopathy. The mortality rate of CACTD was 11/12 (the outcome of one case was not reported). Conclusions c.199-10T>G is the most common SLC25A20 gene mutation reported in Asia population with severe phenotypes and poor outcomes. Early diagnosis and timely treatment of CACTD are crucial. Inborn metabolic diseases such as CACTD should be considered if unexplainable exacerbation of clinical signs in neonatal period, or sudden infant death occurs. Key words: Carnitine acyltransferases; Lipid Metabolism, Inborn Errors; Membrane transport proteins; Mutation