ABSTRACT
Objective@#To detect potential variation in an ethnic Han Chinese family affected with late-onset lipid storage myopathy.@*Methods@#Next generation sequencing (NGS) was used to screen disease-related genes in the proband. Suspected mutation was validated with PCR and Sanger sequencing in two patients, their father, and 100 healthy controls.@*Results@#Heterozygous c. 770A>G (p.Tyr257Cys) and c. 1395dupT (p.Gly466Tryfs) mutation were detected in the two patients. Their father was found to be heterozygous for the c. 770A>G (p.Tyr257Cys) mutation, while the c. 1395dupT (p.Gly466Tryfs) variation was not reported previously and not found among the healthy controls.@*Conclusion@#Mutations of the ETFDH gene probably underlie the pathogenesis in this family. The novel c. 1395dupT (p.Gly466Tryfs) has enriched the mutation spectrum of EDFDH gene.
ABSTRACT
Objective To improve the understanding of clinical phenotype and genotype of multiple acyl-CoA dehydrogenase deficiency (MADD) in neonates.Method The clinical data of a neonates with the diagnosis of MADD and treated in the Neonatal Department of Children's Hospital of Capital Institute of Pediatrics in December 2016 were analyzed.The literature collected from Wanfang database,CNKI and PubMed database from 1976 January to 2017 June was retrieved.Using "glutaric acidemia type Ⅱ ","multiple acyl CoA dehydrogenase deficiency","infant" and "neonate" as the key words.The phenotype and genotype characteristics were summarized.Result This boy was a full-term low birth weight infant with abnormal family history.He was admitted to hospital with recurrent episodes of poor response,respiratory distress and hyperlactacidemia.B-mode ultrasound abdominal examination suggested polycystic kidney disease.Laboratory tests revealed non-kenotic hypoglycemia,refractory metabolic acidosis,elevated lactate and muscle enzymes,hyperammonemia,abnormal coagulation function test.Mass spectrometry analysis showed that multiple acyl-carnitine increased.Urine gas chromatography-mass spectrometry showed significantly increased levels of lactic,glutaric,2-hydroxypentanedioic,dicarboxylic,and 4-hydroxybenzene lactic acids.The infant was given high doses of vitamin B2,L-carnitine,and other symptomatic treatments,but the condition did not improve.He died 5 days later.The gene test showed ETFDH gene compound heterozygous mutations,one missense mutations from the father with normal phenotype c.770A ＞ G (p.Y257C),a frameshift mutation from the mother with normal phenotype c.1281-1282 deletion mutation of AA (p.I428Rfs6).The protein structures of the mutations were predicted to be deleterious.Frameshift mutation c.1281-1282 deletion mutation of AA (p.I428Rfs6) were not included in the gene bank.A total of 21 cases with MADD were found from the literature.The clinical characteristics including:male (76.2％),dyspnea (52.4％),poor response (52.4％),hypoglycemia (47.6％),hepatomegaly (47.6％),elevated muscle enzymes (42.9％),immediate onset within 24 hour of birth (42.9％),abnormal family history (38.1％),malformation (38.1％),hyperammonemia (33.3％),metabolic acidosis (28.6％).81.0％of the patients were given vitamin B2 treatment,71.4％ of carnitine,28.6％ of coenzyme Q10,28.6％ of low fat,low protein and high carbohydrate feeding.However,the prognosis of these patients was poor,76.2％ died,and 42.9％ died within 1 week after birth,and 23.8％ survived.But all showed different degrees of mental retardation during follow-up periods.Conclusion Neonatal onset MADD can be characterized by dyspnea,poor response,hypoglycemia,hepatomegaly and elevated muscle enzymes.The disease is more common in early male neonates.It can be treated with vitamin B2 and L-carnitine,but with poor prognosis and high mortality.In this case,there were 2 sites in the ETFDH gene that formed complex heterozygous mutation:c.770A ＞ G (p.Y257C) and c.1281-1282 deletion mutation of AA (p.I428Rfs6),while the latter is a new mutation.