Three cases of carnitine-acylcarnitine transposase deficiency and literature review

Objective To study the clinical features, biochemical characteristics and gene mutations of patients with (CACTD). Method The clinical data, biochemical markers and gene mutations of three cases with CACTD admitted our hospital in 2017 were retrospectively analyzed. The related literatures were searched from China national knowledge infrastructure, wanfang database, PubMed, national center for biotechnology information and Embase using keywords neonate , infant , carnitine-acylcarnitine deficiency , carnitine-acylcarnitine translocase , and (up to April 2018). Result (1) Three cases (2 boys and 1 girl) with CACTD were full-term infants without asphyxia after birth. The mothers had no abnormal pregnancy, and the parents had no consanguinity. All the patients had poor response and severely hypoglycemia 15~20 hours after birth. Hyperammonemia, elevated liver enzymes and creatine kinase, severe dicarboxylic aciduria, significantly increased level of long-chain acylcarnitine, and significantly decreased concentration of free carnitine were observed in all 3 patients. Significantly decreased serum ketone body was observed in 2 cases. All of them had recurrent atrioventricular block and ventricular tachycardia requiring repeated electrocardioversion, lidocaine, and amiodarone treatment. Arginine, carnitine and special formula with low fat and high medium-chain-triglyceride were given to two infants. Two infants died of cardiorespiratory failure at 3-day and 8-day of life, respectively. The other infant′s clinical condition improved significantly.However, he was discharged from our NICU at the request of his parents. Gene analysis revealed that compound heterozygous mutations c.199-10T>G and IVS7-9_16 ins (a possible novel mutation) were detected in the SLC25A20 gene of case 2. Homozygous mutation c.199-10T>G was identified in the SLC25A20 gene of case 3 whose parents both carried this mutation. (2) A total of 17 articles and 50 cases were retrieved and analyzed. A total of 40 mutations were found in the SLC25A20 gene. Homozygous mutations were found in 23 cases, and compound heterozygous mutations were found in 27 cases. The mutation of c.199-10T>G was the most common mutation and occurred 22 times in the patients from Asia population. Other mutations were found less than 6 times. The review showed that the most common clinical features included hypoketotic hypoglycemia, hyperammonemia, elevated liver enzymes and creatine kinase, remarkable dicarboxylic aciduria, significantly increased level of long-chain acylcarnitine, significantly decreased free carnitine, arrhythmia and cardiomyopathy. Mostly, the onset of symptoms was within 1 week after birth (88%, 44/50). The mortality was 69.8% (30/43). Most patients died within the first year of their life. Conclusion Early recognition, early diagnosis and prompt treatment are crucial for CACTD patients. Gene analysis is a reliable diagnostic method. The mutation of c.199-10T>G is the most common SLC25A20 mutation reported in Asia population. Hypoketotic hypoglycemia is an early sign of this disease. Families with a proband need prenatal diagnosis during the second pregnancy. Key words: Metabolism, inborn errors; Carnitine acyltransferases; Carnitine-acylcarnitine deficiency; SLC25A20 gene; Mutation