Résumé
Objective To study the clinical features,biochemical characteristics and gene mutations of patients with carnitine-acylcarnitine translocase deficiency (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 SLC25A20"(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.
Résumé
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) Thirtytwo 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.
Résumé
Objective@#To investigate the clinical, biochemical and genetic features of four carnitine-acylcarnitine translocase deficiency cases.@*Methods@#Four cases diagnosed with carnitine-acylcarnitine translocase deficiency from Guangxi Maternal and Child Health Hospital were studied. DNA was extracted from dry blood filter for gene analysis. SLC25A20 gene analysis was performed in 1 case and the whole exon sequence analysis was performed in 3 cases.@*Results@#Retrospective study on unrelated carnitine-acylcarnitine translocase deficiency patients, the age of onset was 1-28 d, the age of death were 1.5-30 d, main clinical features were hypoglycemia (4 cases), arrhythmia (2 cases), sudden death (2 cases). Biochemical test showed hypoglycemia (1.2-2.0 mmol/L) , elevated creatine kinase (955-8 361 U/L) and creatine kinase isozyme(199-360 U/L), normal or decreased free carnitine level (3.70-27.07 μmol/L) , elevated long-chain acylcarnitine (palmityl carnitine 1.85-14.84 μmol/L). The gene tests showed that all 4 cases carried SLC25A20 gene c.199-10T> G homozygous mutation, inherited from their parents. By analyzing the haplotype, we found that the mutation loci of C. 199-10T> G were all in the same haplotype.@*Conclusion@#The c.199-10T> G mutation is an important molecular cause of carnitine-acylcarnitine translocase deficiency, which has relatively high frequency in Guangxi population, and is related to the founder effect.