Original Article Journal of Inborn Errors of Metabolism & Screening 2016, Volume 4: 1–8 Incidence of Inborn Errors of Metabolism ª The Author(s) 2016 DOI: 10.1177/2326409816669027 by Expanded Newborn Screening iem.sagepub.com in a Mexican Hospital Consuelo Cantu´-Reyna, MD1,2, Luis Manuel Zepeda, MD1,2, Rene´ Montemayor, MD3, Santiago Benavides, MD3, Hector´ Javier Gonza´lez, MD3, Mercedes Va´zquez-Cantu´,BS1,4, and Hector´ Cruz-Camino, BS1,5 Abstract Newborn screening for the detection of inborn errors of metabolism (IEM), endocrinopathies, hemoglobinopathies, and other disorders is a public health initiative aimed at identifying specific diseases in a timely manner. Mexico initiated newborn screening in 1973, but the national incidence of this group of diseases is unknown or uncertain due to the lack of large sample sizes of expanded newborn screening (ENS) programs and lack of related publications. The incidence of a specific group of IEM, endocrinopathies, hemoglobinopathies, and other disorders in newborns was obtained from a Mexican hospital. These newborns were part of a comprehensive ENS program at Ginequito (a private hospital in Mexico), from January 2012 to August 2014. The retrospective study included the examination of 10 000 newborns’ results obtained from the ENS program (comprising the possible detection of more than 50 screened disorders). The findings were the following: 34 newborns were confirmed with an IEM, endocrinopathies, hemoglobinopathies, or other disorders and 68 were identified as carriers. Consequently, the estimated global incidence for those disorders was 3.4 in 1000 newborns; and the carrier prevalence was 6.8 in 1000. Moreover, a 0.04% false-positive rate was unveiled as soon as diagnostic testing revealed negative results. The most frequent diagnosis was glucose-6-phosphate dehydrogenase deficiency; and in the case of carriers, it was hemoglobinopathies. The benefit of the ENS is clear as it offers prompt treatment on the basis of an early diagnosis including proper genetic counseling. Furthermore, these results provide a good estimation of the frequencies of different forms of newborn IEM, endocrinopathies, hemoglobinopathies, and other disorders at Ginequito. Keywords incidence, expanded newborn screening, inborn errors of metabolism, inherited disorders, retrospective study Introduction 1 Genomi-k SAPI de CV, Monterrey, Nuevo Leo´n, Mexico´ Newborn screening for the detection of inborn errors of meta- 2 Escuela de Medicina Tecnolo´gico de Monterrey, Monterrey, Nuevo Leo´n, bolism (IEM), endocrinopathies, hemoglobinopathies, and other Mexico´ 3 Hospital de Ginecologı´a y Obstetricia SA de CV Monterrey, Nuevo Leo´n, disorders is a public health initiative that aims to identify these Mexico´ diseases in a timely manner, avoiding related complications that 4 Department of Biosystems Science and Engineering ETH Zurich, Basel, may arise if not detected on time. Early intervention is an impor- Switzerland tant step in the management of these diseases, which are directly 5 Escuela de Biotecnologı´a y Ciencias de la Salud, Instituto Tecnolo´gico de associated with affected patients’ final outcomes. Newborn Monterrey, Monterrey, Mexico´ screening uses dried blood spots (DBSs) as samples, which Received April 14, 2016. Accepted for publication April 18, 2016. should be obtained after the first 24 hours of life following 1,2 Corresponding Author: previously established and standardized procedures. The dif- Consuelo Cantu´-Reyna, Genomi-k SAPI de CV, Av Cerro de las Mitras 2411 ferent screened disorders and the nomenclature used in this arti- Col Obispado, Monterrey, Nuevo Leo´n, Mexico,´ 64060. 3 cle, as suggested by Sweetman et al, are provided in Table 1. Email: [email protected] This article is distributed under the terms of the Creative Commons Attribution 3.0 License (http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). 2 Journal of Inborn Errors of Metabolism & Screening Table 1. The IEM, Endocrinopathies, Hemoglobinopathies, and Other Table 1. (continued) Disorders Detected in the Ginequito’s ENS Program.a Detection Detection Method Condition Nomenclature Method Condition Nomenclature Benign hyperphenylalaninemia H-PHE MS/MS Fatty acid oxidation disorder conditions Biopterin defect in cofactor BIOPT(BS) Carnitine acylcarnitine translocase CACT biosynthesis deficiency Biopterin defect in cofactor BIOPT(REG) Carnitine palmitoyltransferase type I CPT IA regeneration deficiency Transient neonatal tyrosinemia TNT Long chain L-3-hydroxyacyl CoA LCHAD Tyrosinemia type I TYR I dehydrogenase deficiency Tyrosinemia type II TYR II 2,4-Dienoyl-CoA reductase DE RED Tyrosinemia type III TYR III deficiency Mixed Other conditions Medium-chain acyl-CoA MCAD technologies Complete biotinidase deficiency BIOT dehydrogenase deficiency Partial biotinidase deficiency BIOT Glutaric acidemia type II GA2 Salt-wasting congenital adrenal CAH Carnitine palmitoyltransferase CPT II hyperplasia type II deficiency Simple virilizing congenital adrenal CAH Short-chain acyl-CoA SCAD hyperplasia dehydrogenase deficiency Primary congenital hypothyroidism CH Short-chain L-3-hydroxyacyl-CoA SCHAD Cystic fibrosis CF dehydrogenase deficiency Galactokinase deficiency GALK Trifunctional protein deficiency TFP Classic galactosemia GALT Very long-chain acyl-CoA VLCAD Galactoepimerase deficiency GALE dehydrogenase deficiency Glucose-6-phosphate G6PD Organic acid disorder conditions dehydrogenase deficiency 3-Hydroxy-3-methyglutaricaciduria HMG Hemoglobin S disease Hb S Glutaric acidemia type I GA Hemoglobin SC disease Hb S/C Isobutyrylglycinuria IBG Hemoglobin S-b thalassemia disease Hb S/bTh Acute isovaleric acidemia Acute IVA Hemoglobin C disease Hb C Chronic isovaleric acidemia Chronic IVA Hemoglobin E disease Hb E 2-Methylbutyrylglycinuria 2MBG 3-Methylcrotonyl-CoA carboxylase 3-MCC Abbreviations: IEM, inborn errors ofmetabolism;MS/MS,tandemmass deficiency spectrometry. aNomenclature adopted from Sweetman et al.3 3-Methylglutaconicaciduria 3MGA Methylmalonyl-CoA mutase MUT deficiency (MUT 0 type) Thanks to the benefits of tandem mass spectrometry Methylmalonyl-CoA mutase MUT (MS/MS), nearly 40 diseases can be diagnosed.4 Detection deficiency (MUT type) programs, such as the one described in this report, began in the Cobalamin disorders Cbl A, B, C, D b-ketothiolase deficiency b KT 1960s using DBSs for phenylketonuria (PKU) detection. A few Acute propionic acidemia Acute PROP years later, maple syrup urine disease (MSUD), homocysti- Chronic propionic acidemia Chronic nuria (HCY), tyrosinemia, galactosemia, and congenital PROP hypothyroidism (CH) were added.2,4 Holocarboxylase synthase deficiency MCD Nowadays, the diseases included in newborn screening pro- Malonic acidemia MAL grams, detected by MS/MS, vary widely among countries. In Argininemia ARG the United States, the implementation of MS/MS is covered in Acute argininosuccinic aciduria Acute ASA Chronic argininosuccinic aciduria Chronic ASA almost all states, each state being in charge of the program 5-Oxoprolinuria 5OXOPRO management. Similarly, it occurs in Canada, where each prov- Citrullinemia type I CIT ince or territory is responsible for its own program. Until July Citrullinemia type II CIT II 2008, all Canadian provinces and territories carried out a Homocystinuria HCY screening for PKU by MS/MS; however, heterogeneity is still Hypermethioninemia MET present for the detection of other IEM.4 Hyperornithinemia– HHH In the case of Europe, the newborn screening for CH and hyperammonemia–homocitrullinuria Classic maple syrup urine disease MSUD PKU constitutes an obligatory requirement for all programs, Intermediate maple syrup urine MSUD and in recent years there has been an increased interest for disease expanding the number of screened diseases. For example, in Classic phenylketonuria PKU Spain, the only IEM detected in all communities is PKU. Since 2001, the MS/MS is being used in Galicia to identify nearly 30 (continued) IEM. This technique is spread across the country; and in 2007, Cantu´-Reyna et al 3 Murcia—for analyzing 15 diseases—and the Basque Coun- diagnosis of the core panel conditions and are clinically rele- try—for analyzing only PKU and medium-chain acyl-CoA vant in spite of the lack of an effective treatment. dehydrogenase (MCAD)—adopted it.4 The incidence of different IEM in Mexico is unknown or Asian countries, such as Singapore and Taiwan, have uncertain due to the lack of nationwide ENS programs.13 The recently incorporated MS/MS in their newborn screening pro- Instituto Nacional de Pediatrı´a and the Universidad Auto´noma grams; while China, South Korea, India, Japan, Malaysia, and de Nuevo Leo´n have undertaken studies pertaining to ENS, Thailand are in the implementation phase.4 which clarify the incidence within the Mexican population. The situation in Latin America is also diverse; some countries Although limited data are available from these investigations, (Chile, Costa Rica, Cuba, and Uruguay) have well-established Mexican health providers and researchers still use this infor- programs supervised by their own health authorities, with a cov- mation and records from different countries to establish their erage of over 98% in the diagnosis, treatment as well as follow- cutoffs for a positive diagnosis.2,12,14-16 up