ABSTRACT
The history of the Newborn Screening Program in Chile begins in 1984, when a pilot plan was developed that demonstrated the feasibility of its implementation. In 1992, the Ministry of Health started a national newborn screening program for phenylketonuria (PKU) and congenital hypothyroidism (CH), and in 1998, this was extended to the entire country. Throughout this period, a total of 2,478,123 newborns (NB) have been analyzed, obtaining initial coverage of 48.8%, which was later increased to 87.7%, and at present it is at 98.7% of all NB of our country. During this period, 131 cases with PKU have been diagnosed, resulting in an incidence of 1:18,916 NB, an average age of diagnosis of 18 ± 10.2 days and average phenylalanine level of 19,9 ± 8.8 mg/dl. In relation to CH, 783 cases have been confirmed, arriving at an incidence of 1:3,163 NB, with average age of diagnosis of 12.5 ± 6.9 days. Due to the good results of the program, the government is evaluating the initiation of an extended pilot program, to introduce other pathologies.
Subject(s)
Congenital Hypothyroidism/diagnosis , Neonatal Screening , Phenylketonurias/diagnosis , Biomarkers/blood , Chile/epidemiology , Congenital Hypothyroidism/blood , Congenital Hypothyroidism/genetics , Congenital Hypothyroidism/therapy , Dried Blood Spot Testing , Forecasting , Genetic Predisposition to Disease , History, 20th Century , History, 21st Century , Humans , Incidence , Infant, Newborn , Neonatal Screening/history , Neonatal Screening/trends , Phenotype , Phenylalanine/blood , Phenylketonurias/blood , Phenylketonurias/epidemiology , Phenylketonurias/genetics , Phenylketonurias/therapy , Predictive Value of Tests , Prognosis , Program Development , Program Evaluation , Thyroid Hormones/blood , Time FactorsABSTRACT
Both the haplotype distribution and the mutational spectrum of the phenylalanine hydroxylase (PAH) gene has been defined for the Chilean phenylketonuria (PKU) population. Mutation analysis was performed using a combined approach of screening for common European and Oriental mutations and application of the DGGE scanning method in the remaining uncharacterized alleles. A total of 16 different mutations have been identified, including two novel ones, Q232X and IVS11nt5. The most frequent mutations were IVS10nt-11 and V388M present both in the 13% of the mutant chromosomes. The rest of the mutations are rare. The haplotype association including VNTR and STR alleles, was examined to investigated the origin and distribution of PAH alleles in Chile. Our results are consistent with Southern Europeans as the major source of PAH mutations in Latin America. However, we have also detected mutations from East and Central Europe, such IVS12nt1, R408W and R252W. It is clear that the PKU mutation present in each Latin American country varies with the demographic profile and specific mutation scanning is necessary in each population both for diagnostic and prognostic purposes. The correlation between the genotypes and the phenotypes is consistent with the emerging pattern of mutation severity deduced from previous studies in related populations.
Subject(s)
Phenylalanine Hydroxylase/deficiency , Chile , DNA Mutational Analysis , Genotype , Haplotypes , Humans , Mutation , Phenotype , Phenylketonurias/geneticsABSTRACT
A screening program for the early diagnosis of phenylketonuria was initiated 24 months ago in the Servicio de Salud Metropolitano Central. Since then, 2 cases with phenylketonuria have been early diagnosed. These patients started their nutritional treatment, consisting of a phenylalanine restricted diet at 14 and 17 days of age. The children are submitted to periodic medical, anthropometric, neurologic, biochemical and psychometric analysis. With a strict control they maintain phenylalanine plasma levels between 2 and 6 mg%. Both patients have a normal psychomotor development at 4.5 and 6.5 months of age and an anthropometric development at p50 of NCHS.
Subject(s)
Phenylketonurias/prevention & control , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Phenylketonurias/diet therapy , Phenylketonurias/physiopathologyABSTRACT
A screening program for phenylketonuria in newborn infants that is being carried out at one of the Metropolitan Health Services at Santiago, Chile for the last 17 months, using the Guthrie test, is described. During this period 15,214 blood samples have been analyzed, which represented 94.4% coverage for beneficiary newborn infants. Two cases of transient hyperphenylalaninemia, one patient with benign hyperphenylalaninemia, and one infant with classical phenylketonuria have been thus identified. In this last child nutritional management was started at 13 days of life. Screening programs for early detection of phenylketonuria in Chile seem convenient, feasible and reliable.
