Screening for hereditary tyrosinemia and genotype analysis in newborns.
- Author:
Fan TONG
1
;
Rulai YANG
1
;
Chang LIU
1
;
Dingwen WU
1
;
Ting ZHANG
1
;
Xinwen HUANG
1
;
Fang HONG
1
;
Guling QIAN
1
;
Xiaolei HUANG
1
;
Xuelian ZHOU
1
;
Qiang SHU
1
;
Zhengyan ZHAO
1
Author Information
1. Zhejiang Neonatal Screening Center, Department of Genetic and Metabolic Disease, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China.
- Publication Type:Journal Article
- MeSH:
Child;
Cyclohexanones;
therapeutic use;
Genotype;
Humans;
Infant;
Infant, Newborn;
Neonatal Screening;
Nitrobenzoates;
therapeutic use;
Tandem Mass Spectrometry;
Tyrosinemias;
diagnosis;
drug therapy;
genetics
- From:
Journal of Zhejiang University. Medical sciences
2019;48(4):459-464
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To analyze the results of screening for hereditary tyrosinemia (HT) in newborns and its clinical features and genotype.
METHODS:The HT screening was conducted among 2 188 784 newborns from November 2013 to November 2018. The tyrosine (TYR)/ succinylacetone (SA) levels were detected by tandem mass spectrometry (MS-MS). The clinical characteristics, genetic results and following up data of identified patients were analyzed.
RESULTS:The normal ranges (0.5%-95.5%) of TYR and SA were 34.5-280.0 μmol/L and 0.16-2.58 μmol/L, respectively. Three HT cases were confirmed with a detection rate of 1∶729 595. There was 1 case of tyrosinemia type Ⅰ (HTⅠ) (homozygous variations of c.455G>A in gene), 1 case of tyrosinemia type Ⅱ(HTⅡ) (heterozygous variations of c.890G>T and c.408+1G>A in gene), and 1 case of tyrosinemia type Ⅲ (HT Ⅲ) (homozygous variations of c.257T>C in gene). The variations of c.890G>T, c.4081G>A of and c.257T>C of were novel. The positive predictive value of the screening was 3.4%. Case 1 (HTⅠ) with TYR and SA values of 666.9 μmol/L and 3.87 μmol/L respectively, presented cholestasis, mild elevated of liver enzyme and lactic acid, who were although fed with TYR and phenylalanine free milk, but died at 2 months of age. Case 2 (HTⅡ) with higher TYR (625.6 μmol/L) and normal SA at screening, received medical milk treatment; during the 7 months of follow-up the baby showed normal score of Bayley assessment and normal TYR without eye and skin symptoms. Case 3 (HT Ⅲ) with TYR of 1035.3 μmol/L and normal SA at screening; during the 29 months of follow-up the value of TYR fluctuated from 532.1 μmol/L to 1060.3 μmol/L due to irregular medical milk treatment, while the score of Bayley assessment was normal.
CONCLUSIONS:HT is rare in the southern Chinese population, and the gene spectrum is scattered. Early treatment with nitisinone is recommended in children with HTⅠ, otherwise the prognosis is poor; the prognosis of children with HTⅡ is good when early treated with special diet; the prognosis of children with HTⅢ needs to be determined with more data.
