Clinical and genetic characteristics of primary carnitine deficiency identified by neonatal screening / 中华医学遗传学杂志

OBJECTIVE@#To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD).@*METHODS@#From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up.@*RESULTS@#In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c.1484T>C, c.394-1G>T, c.431T>C and c.265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c.1400C>G (42.3%), c.760C>T (11.5%) and c.51C>G (7.7%). During the 8-42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment.@*CONCLUSION@#The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c.1400C>G. Above finding has enriched the spectrum of SLC22A5 gene mutations.

Clinical and genetic characteristics of primary carnitine deficiency identified by neonatal screening / 中华医学遗传学杂志

Objective@#To study the prevalence, clinical and genetic characteristics of primary carnitine deficiency (PCD).@*Methods@#From January 2013 to December 2017, 720 667 newborns and their mothers were tested for PCD by tandem mass spectrometry. Potential mutations of carnitine transporter gene SLC22A5 among suspected PCD patients were analyzed. Dietary guidance and L-carnitine supplementation were provided to the parents. Growth and intelligence development were surveyed during follow-up.@*Results@#In total 21 neonates and 6 mothers were diagnosed with PCD, which yielded an incidence of 1 in 34 317. Eighteen SLC22A5 mutations were detected, which included 4 novel mutations, namely c. 1484T>C, c. 394-1G>T, c. 431T>C and c. 265-266insGGCTCGCCACC. Eighteen patients were found to carry compound heterozygous mutations and 3 have carried homozygous SLC22A5 mutations. Three mothers carried compound heterozygous mutations and 2 carried homozygous mutations. Common mutations included c. 1400C>G (42.3%), c. 760C>T (11.5%) and c. 51C>G (7.7%). During the 8 ~ 42 month follow-up, neonates with PCD showed no clinical symptoms but normal growth. Blood level of free carnitine was raised in all mothers after the treatment.@*Conclusion@#The incidence of neonatal PCD in Henan is 1 in 34 317, with the most common mutation being c. 1400C>G. Above finding has enriched the spectrum of SLC22A5 gene mutations.

Genotype and phenotype correlation of phenylalanine hydroxylase deficiency among patients from Henan / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To delineate the mutation spectrum of phenylalanine hydroxylase (PAH) gene among patients affected with phenylalanine hydroxylase deficiency (PAHD) in Henan Province of China, and to explore the correlation between the genotype and the phenotype.</p><p><b>METHODS</b>A total of 155 affected children were recruited. Potential mutation of the PAH gene were analyzed by direct sequencing. The genotype-phenotype correlation was analyzed by matching the expected and observed phenotypes.</p><p><b>RESULTS</b>Over 72 mutations and 108 genotypes have been identified. There were 7 homozygous mutations, including 1 case with EX6-96A>G/EX6-96A>G, 1 with R241C/R241C, 1 with R413P/R413P, and 4 with R243Q/R243Q. Among these, 6 patients have presented classic PKU phenotypes, except for a R241C/R241C genotype which has led to mild PKU. In 104 patients carrying compound PAH mutations, 52 were classic, 34 were mild and 39 had mild HPA. Patients who were heterozygous for EX6-96A>G/R241C, R243Q/A434D, EX6-96A>G/R413P and EX6-96A>G/ R241C were found with both the classic PKU and mild PKU phenotypes. Common mutations associated with mild HPA have included R53H, R243Q, V399V and H107R. The common mutations associated with mild PKU included R243Q, R241C, EX6-96A>G, and IVS4-1G>A. The prevalent mutations in classic PKU were R243Q, EX6-96A>G and V399V. The consistency between prediction of the biochemical genotype and observed phenotype was 77.78%, especially in classic PKU, the consistency was up to 82.14%. Significant correlations were disclosed between pretreatment levels of phenylalanine and AV sum (r=-0.6729, P < 0.01).</p><p><b>CONCLUSION</b>The mutation spectrum of PAH gene in Henan seems to differ from that of other regions. Independent assortment of mutant alleles may result in a complex genotype-phenotype correlation, but the genotypes of PAHD patients have correlated with the phenotype.</p>