The importance of inherited metabolic disease screening in the treatment and diagnosis of infantile cholestatic hepatopathy / 中国小儿急救医学

Objective To assess the significance of screening for inherited metabolic diseases in the treatment and diagnosis of infantile cholestatic hepatopathy,and to analyze the biochemical changed character‐istics of patients who were diagnosed with gene mutations. Methods From January 2016 to January 2017,69 children who were diagnosed as intrahepatic cholestasis in the Pediatric Gastroenterology Department of Shengjing Hospital Affiliated to China Medical University were enrolled. The medical history,physical exami‐nation,biochemical test and genetic metabolism screening results were recorded. Results Sixty‐seven cases of 69 children made tandem mass spectrometry(MS/MS),gas chromatography‐mass spectrometry(GC/MS) or genetic testing. Compared with the normal hereditary metabolic disease screening group, the abnormal group had higher levels of alkaline phosphatase,total bilirubin,direct bilirubin,and total bile acid,the differ‐ence was statistically significant (P<0. 05). The most common abnormal in MS/MS were elevation of free carnitines and arginine,citrulline,methionine,and the most common abnormal in GC/MS were elevation of 3‐hydroxyl propionic acid,4‐hydroxyl phenyllactic acid,4‐hydroxyl phenylacetic acid. In 6 children with posi‐tive genetic test results,the MS/MS and GC/MS of 4 neonatal intrahepatic cholestasis caused by citrin defi‐ciency showed aminoacidemia(citrullinemia,tyrosinemia) and elevations of urine organic acids. Five muta‐tions of SLC25A13 gene were found in the neonatal intrahepatic cholestasis caused by citrin deficiency pa‐tients,including IVS6+5G >A,851del4,IVS11 +1G >A,851 854de and 852 855del. The main clinical manifestations of progressive familial intrahepatic cholestasis type 2 ( PFIC2) were cholestatic jaundice and pruritus,γ‐glutamyl transpeptidase was normal,and with the c. 667C>T defection in the ABCB11 gene. The TALDO1 gene mutation type of one transaldolase deficiency was c. 716G>A and c. 854dupA heterozygous mutation. Conclusion MS/MS and GC/MS play a vital role in the early identification of cholestasis caused by genetic and metabolic disorders. Genetic testing can provide accurate diagnosis for rare genetic metabolic diseases.

Clinical research of neonatal intrahepatic cholestasis caused by Citrin deficiency in Hubei Province / 中华实用儿科临床杂志

Objective To explore the clinical manifestations and the characteristics of neonatal intrahepatic cholestasis caused by Citrin deficiency(NICCD)in Hubei province. Methods The biochemical indicators including liver function,blood lipid,lactic acid,blood ammonia,total bile acid,alpha feto protein,coagulogram,blood amino spec-trum,acylcrnitine spectrum,urine organic acid and SLC25A13 gene analysis of 20 cases with NICCD,who came from Wuhan Children's Hospital,during September 2010 to January 2013,were collected before treatment,then followed up for 1 year. Results Laboratory results of NICCD patients showed high blood bilirubin,elevated liver enzymes and bile acid,hyperlipidemia,high alpha feto protein,high lactic acidosis,high ammonia,hypoalbuminemia,hypoglycemia,disor-der of blood coagulation mechanism,variety of amino acids increase,mainly citrulline rose. Mainly long - chain acyl carnitine increased among acyl of carnitine. Abnormal increase of urine 4 - hydroxy benzene acetic acid,4 - hydroxy benzene lactic acid and 4 - hydroxy benzene pyruvic acid. Six mutations were detected in SLC25A13 gene analysis,and L477R,G639S of them were novel mutations,851del4,1638ins23,IVS6 + 5G ﹥ A were hot mutation. All the patients were eased in jaundice before they were 1 year old. Conclusions The early clinical criterion of the patients is disor-der. Hyperlipidemia has been detected in the early course of the disease,and L477R,G639S are the novel mutations.

Neonatal intrahepatic cholestasis caused by Citrin deficiency / 中华实用儿科临床杂志

Neonatal intrahepatic cholestasis caused by Citrin deficiency(NICCD) is one of phenotypes of Citrin deficiency.It's an autosomal recessive disorder which was mainly seen in East Asia,including China.Case of NICCD was reported firstly by Japanese in 2001.In south area of China,the morbidity of NICCD is higher than that in north area of China.Most of the patients with NICCD has benign prognosis.Symptoms resolve within the first year of life,thus making a diagnosis difficult after this time.But few of patients will develop liver failure,even be fatal to life.Early diagnosis,regular follow-up and proper management may improve the prognosis.

Advances of citrin deficiency / 国际儿科学杂志

Citrin deficiency,caused by mutations in SLC25A13,is an autosomal recessive genetic disorder with two age-related phenotypes:adult-oneset type Ⅱ citrullinemia and neonatal intrahepatic cholestasis.Recently,it has been found mostly in individuals of East Asian ancestry.In south China,there is a high mutation carrier frequency especially.There is still a lack of criteria for clinical or biochemical diagnosis of this disease,gene analysis is the main basis of the current diagnosis consequently.Surging number of case reports indicate that Citrin deficiency is not a self-limited disease.Early diagnosis and proper treatments may improve the prognosis.This paper focuses on the current researches in order to make further comprehensiom.

Progress in mechanisms of citrin deficiency / 国际儿科学杂志

Citrin deficiency is an autosomal recessive disorder caused by mutations of the SLC25A13 gene.As a calcium binding mitochondrial aspartate glutamate carrier,Citrin plays an important role not only in the urea synthesis but NADH shuttle as well.Citrin deficiency has two phenotypes:adult-onset typeⅡcitrullinemia and neonatal intrahepatic cholestasis.Citrin deficiency is a common congenital metabolic defect first found in Japan and now is considered as a global disease.