RESUMEN
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency has been a target of expanded newborn screening (ENBS) using tandem mass spectrometry in Japan. Since the implementation of ENBS, a number of novel ACADVL variants responsible for VLCAD deficiency have been identified. In this study, genotypic differences in Japanese patients with VLCAD deficiency were investigated before and after ENBS. The ACADVL variants in 61 subjects identified through ENBS (ENBS group) and in 40 patients who subsequently developed clinical symptoms without undergoing ENBS (pre-ENBS group) were compared. Subjects in the ENBS group underwent genetic testing and/or VLCAD enzyme activity measurements. Patients in the pre-ENBS group were stratified into three clinical phenotypes and underwent genetic testing. This study revealed that the variants p.K264E, p.K382Q and c.996dupT were found in both groups, but their frequencies were lower in the ENBS group (5.2%, 3.1% and 4.2%, respectively) than in the pre-ENBS group (16.5%, 12.7% and 10.1%, respectively). In addition, p.C607S, p.T409M, p.M478I, p.G289R, p.C237R, p.T260M, and p.R229* were exclusively identified in the ENBS group. Among these variants, p.C607S exhibited the highest frequency (18.8%). The patients who were heterozygous for p.C607S demonstrated 7-42% of control enzyme activity. p.C607S is suspected to be unique to Japanese individuals. According to a comparison of enzyme activity, patients with the p.C607S variant may exhibit higher enzyme activity than those with the p.A416T, p.A180T, p.R450H, and p.K264E variants, which are responsible for the myopathic form of the disease. The VLCAD deficiency genotypes have changed since the initiation of ENBS in Japan.
Asunto(s)
Síndromes Congénitos de Insuficiencia de la Médula Ósea , Errores Innatos del Metabolismo Lipídico , Enfermedades Mitocondriales , Enfermedades Musculares , Acil-CoA Deshidrogenasa/genética , Acil-CoA Deshidrogenasa de Cadena Larga/genética , Síndromes Congénitos de Insuficiencia de la Médula Ósea/epidemiología , Humanos , Recién Nacido , Japón/epidemiología , Errores Innatos del Metabolismo Lipídico/epidemiología , Enfermedades Mitocondriales/epidemiología , Enfermedades Musculares/epidemiología , Tamizaje Neonatal/métodosAsunto(s)
Síndromes Congénitos de Insuficiencia de la Médula Ósea/genética , Elastasa de Leucocito/genética , Neutropenia/congénito , Médula Ósea/patología , Síndromes Congénitos de Insuficiencia de la Médula Ósea/epidemiología , Síndromes Congénitos de Insuficiencia de la Médula Ósea/patología , Síndromes Congénitos de Insuficiencia de la Médula Ósea/terapia , Manejo de la Enfermedad , Humanos , Lactante , Masculino , Mutación , Neutropenia/epidemiología , Neutropenia/genética , Neutropenia/patología , Neutropenia/terapia , Tanzanía/epidemiologíaAsunto(s)
Síndromes Congénitos de Insuficiencia de la Médula Ósea/epidemiología , Infecciones/epidemiología , Neutropenia/congénito , Neutrófilos/patología , Enfermedades de Inmunodeficiencia Primaria/epidemiología , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Neutropenia/epidemiología , Recurrencia , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: To determine the incidence of newborn screening (NBS) disorders and to study the key performance indicators of the program. METHODS: This retrospective single-center study enrolled all infants who underwent NBS from January 2012 to December 2017 at Prince Sultan Military Medical City, Riyadh, Saudi Arabia. We screened 17 NBS disorders. Blood samples were collected 24 hours after birth. If the initial result was positive, a second sample was collected. True positive cases were immediately referred for medical management. Data were extracted from laboratory computerized and non-computerized records using case report forms. RESULTS: During the study period, 56632 infants underwent NBS with a coverage rate of 100%. Thirty-eight cases were confirmed. The incidence of congenital hypothyroidism was 1:3775. The positive predictive value for the detection of congenital hypothyroidism was 11.8%. Propionic aciduria was the most common metabolic disorder, with an incidence of 1:14158. Very long-chain acyl CoA dehydrogenase deficiency and glutaric aciduria type 1 had an incidence of 1:18877 each. Phenylketonuria, biotinidase deficiency, maple syrup urine disease, and citrullinemia had an incidence of 1:28316 each. However, galactosemia and 3-methyl crotonyl carboxylase deficiency had the lowest incidence of 1:56632. CONCLUSION: The NBS coverage rate at our facility was 100%. Congenital hypothyroidism was the most frequently detected disorder with an incidence that matches worldwide figures. The incidence of other inherited disorders was consistent with regional figures.
Asunto(s)
Enfermedades del Recién Nacido/diagnóstico , Enfermedades del Recién Nacido/epidemiología , Tamizaje Neonatal , Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Biomarcadores/sangre , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/epidemiología , Síndromes Congénitos de Insuficiencia de la Médula Ósea/diagnóstico , Síndromes Congénitos de Insuficiencia de la Médula Ósea/epidemiología , Glutaril-CoA Deshidrogenasa/deficiencia , Humanos , Hipotiroidismo/diagnóstico , Hipotiroidismo/epidemiología , Incidencia , Recién Nacido , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/epidemiología , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/epidemiología , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/epidemiología , Valor Predictivo de las Pruebas , Acidemia Propiónica/diagnóstico , Acidemia Propiónica/epidemiología , Estudios Retrospectivos , Arabia Saudita/epidemiología , Factores de TiempoRESUMEN
Background Fatty acid ß-oxidation disorders (FAODs) include more than 15 distinct disorders and have a wide variety of symptoms, usually not evident between episodes of acute decompensation. After the introduction of newborn screening (NBS) using tandem mass spectrometry (MS/MS), early identification of FAODs has become feasible. We analyzed the MS/MS results in Tianjin, China during a six-year period to evaluate the incidence, disease spectrum, and genetic characteristics of FAODs. Methods We analyzed the MS/MS results for screening FAODs from May 2013 to December 2018 in Tianjin, China. Infants with positive screening results were confirmed through next-generation sequencing and validated by Sanger sequencing. Results A total of 220,443 infants were screened and 25 FAODs patients were identified (1:8,817). Primary carnitine deficiency (PCD) with an incidence rate up to 1:20,040 was the most common disorder among all FAODs. Recurrent mutations of relatively common diseases, like PCD and short-chain acyl-CoA dehydrogenase deficiency (SCADD), were identified. During the follow-up, two patients suffered from sudden death due to carnitine palmitoyl transferase-â ¡ deficiency (CPT â ¡) and very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD). Conclusion Our data indicated that FAODs are relatively common in Tianjin and may even cause infant death in certain cases. The elucidated disease spectrum and genetic backgrounds elucidated in this study may contribute to the treatment and prenatal genetic counseling of FAODs.