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BACKGROUND: Septo-optic dysplasia (SOD), also known as de-Morsier syndrome, is a rare disorder characterized by any combination of optic nerve hypoplasia, pituitary gland hypoplasia, and midline abnormalities of the brain including absence of the septum pellucidum and corpus callosum dysgenesis. The variable presentation of SOD includes visual, neurologic, and/or hypothalamic-pituitary endocrine defects. The unclear aetiology of a large proportion of SOD cases underscores the importance of identifying novel SOD-associated genes. CASE PRESENTATION: To identify the disease-causing gene in a male infant with neonatal hypoglycaemia, dysmorphic features, and hypoplasia of the optic nerve and corpus callosum, we designed a targeted next-generation sequencing panel for brain morphogenesis defects. We identified a novel hemizygous deletion, c.6355 + 4_6355 + 5delAG, in intron 38 of the FLNA gene that the patient had inherited from his mother. cDNA studies showed that this variant results in the production of 3 aberrant FLNA transcripts, the most abundant of which results in retention of intron 38 of FLNA. CONCLUSIONS: We report for the first time a case of early-onset SOD associated with a mutation in the FLNA gene. This finding broadens the spectrum of genetic causes of this rare disorder and expands the phenotypic spectrum of the FLNA gene.
Assuntos
Filaminas/genética , Estudos de Associação Genética , Mutação , Displasia Septo-Óptica/genética , Sequência de Bases , Encéfalo , Corpo Caloso/diagnóstico por imagem , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Nervo Óptico , RNA Mensageiro/metabolismo , Displasia Septo-Óptica/diagnóstico por imagem , Displasia Septo-Óptica/fisiopatologia , Septo PelúcidoRESUMO
Nowadays, health funding decisions must be supported by sound arguments in terms of both effectiveness and economic criteria. After more than half a century of newborn screening for rare diseases, the appropriate economic evaluation framework for these interventions is still challenging. The validity of standard methods for economic evaluation heavily relies on the availability of robust evidence, but collection of such evidence is precluded by the rareness of the conditions that may benefit from screening. Furthermore, there are a series of conceptual and methodological limitations that warrant further careful consideration when assessing the cost-effectiveness of newborn screening programs. In this chapter we provide a general overview of current economic evaluation methods and the challenges for their application to newborn screening programs.
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Custos de Cuidados de Saúde , Triagem Neonatal/economia , Triagem Neonatal/métodos , Doenças Raras/diagnóstico , Doenças Raras/economia , Deficiência de Biotinidase/diagnóstico , Deficiência de Biotinidase/economia , Deficiência de Biotinidase/terapia , Análise Custo-Benefício , Humanos , Incidência , Recém-Nascido , Modelos Econômicos , Valor Preditivo dos Testes , Prevalência , Prognóstico , Anos de Vida Ajustados por Qualidade de Vida , Doenças Raras/terapiaAssuntos
Doenças em Gêmeos/diagnóstico , Doenças em Gêmeos/etiologia , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/etiologia , Método Canguru , Taquicardia/diagnóstico , Taquicardia/etiologia , Diagnóstico Diferencial , Eletrocardiografia/métodos , Feminino , Humanos , Recém-Nascido , Decúbito DorsalRESUMO
Adamowicz and colleagues raised the alert in 2007 about patients with atypical hereditary fructose intolerance (HFI) primarily misdiagnosed as CDG Ix. We describe a girl with neonatal hypertonia, facial trismus, absent swallowing and coughing reflexes, gastro-oesophageal reflux and sporadically elevated Krebs cycle metabolites and lactate. At 14 months microcephaly and hepatomegaly were noted, with hypertransaminasaemia but normal blood coagulation, glucose, phosphate, and absent urinary reducing substances. Neurological impairment persisted. Because of hepatic and neurological abnormalities with developmental delay, Tf IEF was performed and showed a severe type 1 pattern, resulting in a wrong diagnosis of CDG. Subsequently, an aversion to fruits suggested HFI, confirmed by the finding of ALDOB mutations (p.A150P/p.N335K). The girl improved with fructose-free diet, but liver cirrhosis led to hepatic transplantation. She is now 7 years old with good evolution; facial trismus and hypertonia reversed, but microcephaly persists. Transferrin MALDI-TOF MS characterization revealed underoccupation of glycosylation sites and glycan abnormalities, which reversed with dietary treatment. High maternal fructose concentrations might have caused neonatal abnormalities. Although in our patient's mother there is no fructose accumulation at present, it is possible that increased ingestion of fruits and vegetables during pregnancy, together with her heterozygosity, caused an accumulation of fructose that finally affected the fetus. We also describe slightly abnormal transferrin isoelectric focusing and MALDI-TOF MS patterns of intact transferrin and N-glycans in a fructose-1,6-bisphosphatase (FBP1)-deficient patient. While HFI is a well-known cause of secondary CDG, we found no reports of abnormal transferrin isoelectric focusing patterns in FBP1 deficiency and we introduce this condition as a possible secondary cause for altered transferrin isoelectric focusing.
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Intolerância à Frutose/genética , Intolerância à Frutose/metabolismo , Criança , Pré-Escolar , Defeitos Congênitos da Glicosilação/diagnóstico , Erros de Diagnóstico , Feminino , Intolerância à Frutose/diagnóstico , Frutose-Bifosfato Aldolase/genética , Glicosilação , Humanos , Lactente , Recém-Nascido , Focalização Isoelétrica , Mutação , Gravidez , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Trombocitopenia/diagnóstico , Transferrina/química , Transferrina/metabolismoRESUMO
Symptomatic hyperammonaemia in newborn is a medical emergency that should be recognised in its early stages, specifically diagnosed and aggressively treated to improve the immediate and long-term prognosis of these children. The paediatrician and the neonatal doctor should have a diagnosis-therapy scheme for its urgent management.
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Tratamento de Emergência , Hiperamonemia/diagnóstico , Hiperamonemia/terapia , Árvores de Decisões , Humanos , Hiperamonemia/etiologia , Recém-NascidoRESUMO
BACKGROUND: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. METHODS: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. RESULTS: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. CONCLUSION: This study describes the natural history of classic galactosemia based on the hitherto largest data set.
Assuntos
Galactosemias/patologia , UTP-Hexose-1-Fosfato Uridililtransferase/genética , Adolescente , Adulto , Estudos de Coortes , Feminino , Galactosemias/genética , Homozigoto , Humanos , Recém-Nascido , Masculino , Mutação/genética , Triagem Neonatal , Sistema de Registros , Estudos Retrospectivos , Adulto JovemRESUMO
The Expanded Newborn Screening Program (MS/MS) in the region of Galicia (NW Spain) was initiated in 2000 and includes the measurement of methionine levels in dried blood spots. Between June 2000 and June 2007, 140 818 newborns were analysed, and six cases of persistent hypermethioninaemia were detected: one homocystinuria due to cystathionine ß-synthase (CßS) deficiency, and five methionine adenosyltransferase I/III (MAT I/III) deficiencies. The five cases of MAT I/III deficiency represent an incidence of 1/28 163 newborns. In these five patients, methionine levels in dried blood spots ranged from 50 to 147 µmol/L. At confirmation of the persistence of the hypermethioninaemia in a subsequent plasma sample, plasma methionine concentrations were moderately elevated in 4 of the 5 patients (mean 256 µmol/L), while total homocysteine (tHcy) was normal; the remaining patient showed plasma methionine of 573 µmol/L and tHcy of 22.8 µmol/L. All five patients were heterozygous for the same dominant mutation, R264H in the MAT1A gene. With a diet not exceeding recommended protein requirements for their age, all patients maintained methionine levels below 300 µmol/L. Currently, with a mean of 2.5 years since diagnosis, the patients are asymptomatic and show developmental quotients within the normal range. Our results show a rather high frequency of hypermethioninaemia due to MAT I/III deficiency in the Galician neonatal population, indicating a need for further studies to evaluate the impact of persistent isolated hypermethioninaemia in neonatal screening programmes.
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Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Metionina Adenosiltransferase/deficiência , Metionina/sangue , Triagem Neonatal/métodos , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Erros Inatos do Metabolismo dos Aminoácidos/dietoterapia , Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Erros Inatos do Metabolismo dos Aminoácidos/genética , Biomarcadores/sangue , Desenvolvimento Infantil , Pré-Escolar , Diagnóstico Precoce , Feminino , Predisposição Genética para Doença , Homocisteína/sangue , Humanos , Lactente , Recém-Nascido , Masculino , Metionina Adenosiltransferase/sangue , Metionina Adenosiltransferase/genética , Mutação , Linhagem , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Espanha , Espectrometria de Massas em Tandem , Regulação para CimaRESUMO
Mucopolysaccharidosis are multisystem diseases that require large multidisciplinary teams for their care. Specific recommendations are therefore needed for the transition from childhood to adulthood in this patient group. To overcome the barriers that might arise during the transition, the authors consider it essential to implement a flexible plan with a coordinator for the entire process, systematising the information through a standardised paediatric discharge report and educating the patient and their family about the disease, showing the characteristics of the healthcare system in this new stage. The final objective is that, once the transition to adulthood has been completed, the patient's autonomy and potential development are maximised and that the patient receives appropriate healthcare during this transition.
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The response to tetrahydrobiopterin (BH4) in patients with phenylalanine hydroxylase (PAH, EC 1.14.16.1) deficiency (OMIM 261600) has been widely reported. Here we report results of the BH4 loading test (20 mg/kg per day) in a group of 36 patients with PAH deficiency and phenotype of mild hyperphenylalaninaemia (HPA), mild phenylketonuria (PKU) or classic PKU. The patients ranged from neonates aged 7-15 days, detected in the Newborn Screening Programme for PKU in the population of Galicia (NW Spain), to adults aged up to 32 years who had been receiving a low-phenylalanine (Phe) diet for a period of years. Ten of the 36 patients showed a reduction of more than 30% in plasma Phe levels within 24 h of BH4 loading (ranging from 33.7% to 90.2%, mean 59.2%, SD 19.8%). All the patients with mild HPA (100%) showed a positive response; 57% of patients with mild PKU (4 of 7) showed a positive response. Of particular interest were positive responses in two patients with classic PKU, and in one patient with mutations of the phenylalanine hydroxylase (PAH) gene that have not to date been reported to be BH4-responsive (p.S303A and p.G46S). BH4 treatment (5-8 mg/kg per day) was commenced in 9 of the 10 BH4-responsive patients. The observed responses to treatment argue for application of the BH4 loading test in all patients with HPA or PKU, independently of genotype, phenotype or age.
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Biopterinas/análogos & derivados , Dieta com Restrição de Proteínas , Fenilalanina/sangue , Fenilcetonúrias/diagnóstico , Fenilcetonúrias/tratamento farmacológico , Adulto , Biopterinas/uso terapêutico , Humanos , Recém-Nascido , Mutação , Seleção de Pacientes , Fenilalanina Hidroxilase/genética , Fenilalanina Hidroxilase/metabolismo , Fenilcetonúrias/dietoterapia , Fenilcetonúrias/metabolismo , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Patent ductus arteriosus (PDA) is a common problem in preterm newborns. Left vocal cord paralysis (LVCP) can complicate surgical closure if the recurrent nerve is damaged. MATERIALS AND METHODS: A retrospective case series study was conducted on preterm babies diagnosed with PDA in our unit from 1999 to 2013. Their clinical features and treatment complications were reviewed. In those patients that received surgical treatment a telephone questionnaire on the symptoms of LVCP symptoms was completed, and laryncoscopy examination offered. RESULTS: A total of 88 subjects diagnosed with PDA were found, of whom 13.64% (12/88) needed surgery. These patients had a lower gestational age and birth weight. They required mechanical ventilation more frequently, and they had more complications such as, diaphragmatic paralysis, bronchopulmonary dysplasia and intraventricular hemorrhage. One third (3/9) of the surgically treated patients had LVCP, and all of them had dysphonia (100% vs. 16.7%, p=.05). DISCUSSION: LVCP is a common complication of PDA surgery. Further studies are needed to determine its risk factors and its short and long-term consequences.
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Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Permeabilidade do Canal Arterial/cirurgia , Doenças do Prematuro/etiologia , Complicações Pós-Operatórias/etiologia , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Paralisia das Pregas Vocais/etiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Traumatismos do Nervo Laríngeo Recorrente/complicações , Estudos RetrospectivosRESUMO
Maple syrup urine disease (MSUD) is a rare metabolic disorder for which the newborn screening (NBS) is possible but it has not been yet implemented for most Spanish regions. In the present study, we assess the clinical features and outcome of 14 MSUD Spanish patients with similar treatment protocol diagnosed either by NBS or by clinical symptoms. Eight patients were detected by NBS, four classic and four moderate MSUD. The average age at detection was 4.6 days, the mean plasmatic concentration of leucine at diagnosis was 1807 µM; the average number of days with leucine >1000 µM was 0.7 (0-4) and the mean number of total hospitalizations was 1.6 (0-5). Mean follow-up time was 70 months. They had good evolution: all remain asymptomatic, but 2 patients have attention deficit and hyperactivity disorder. Six patients with late diagnosis of classic MSUD were followed during 41 months. All presented with acute encephalopathy during the first month of life, mean leucine levels of 2355 µM, mean number of days with leucine >1000 µM of 6.6 (1-13) and mean number of total hospitalizations of 5.3 (4-7). Only two patients have a psychomotor development index in the lower limit (80 and 83). For all patients a good genotype-phenotype correlation was found and four novel mutations were identified: p.A311H, p.T84S, p.T397L, pL398P. Our study support that NBS improves prognosis of MSUD patients. But early diagnosis and an aggressive treatment together with a close monitoring of leucine levels improve neurological evolution in MSUD patients, even for those not detected by NBS.
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Doença da Urina de Xarope de Bordo/complicações , Doença da Urina de Xarope de Bordo/diagnóstico , Triagem Neonatal/métodos , Encefalopatias/epidemiologia , Encefalopatias/etiologia , Cromatografia por Troca Iônica , Diagnóstico Tardio , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Diagnóstico Precoce , Feminino , Estudos de Associação Genética , Humanos , Recém-Nascido , Leucina/sangue , Masculino , Doença da Urina de Xarope de Bordo/genética , Reação em Cadeia da Polimerase , Prognóstico , Qualidade de Vida , Doenças Raras/complicações , Doenças Raras/diagnóstico , Doenças Raras/genética , Espanha , Espectrometria de Massas em TandemRESUMO
Genotyping of the phenylalanine hydroxylase (PAH) gene offers a new tool for characterizing patients with phenylketonuria (PKU), refining the diagnosis and aiding in the prediction of the clinical outcome and in the implementation of a more adequate treatment. The primary goal of this work was the detailed study of the different allele combinations and the metabolic phenotypes in Spanish PKU patients in order to understand better the clinical heterogeneity of PAH deficiency in our population. The results show that the disease phenotype is a consequence of a combination of mutations at the PAH locus and this observation is valid throughout the spectrum of clinical and biochemical varieties found in Spanish PKU patients. A stronger correlation was found between the predicted residual activity, when known from previous in vitro studies of the mutant proteins, and the Phe tolerance than between the predicted residual activity and the inverse of Phe levels at diagnosis. The observed genotype-phenotype correlations and the available data on the in vitro residual activity of the mutant proteins has enabled the estimation of the severity of most of the mutations found in Spain. This study includes relevant data for clinicians and pediatricians adding to the present knowledge which relates allelic PAH genotypes to biological phenotypes.
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Mutação , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/genética , Heterogeneidade Genética , Genótipo , Humanos , Fenótipo , Fenilalanina Hidroxilase/metabolismo , Fenilcetonúrias/enzimologia , População , EspanhaRESUMO
To evaluate the contribution of organic matter, oxides, and clay fraction to Zn adsorption in six soils from Galicia (Spain), after soil characterization, adsorption isotherms were obtained by adding nine solutions containing between 20 and 500 mg L(-1) concentrations of Zn(NO(3))(2). Distribution coefficients were obtained from the data of adsorption isotherms. Zn adsorption isotherms corresponding to untreated soil and to the organic matter removed samples and organic matter and oxides removed samples were compared with curves pattern and adjusted to Langmuir and Freundlich empirical models. Untreated soils described L-curves whereas when soils were deprived of any component, the curves described were S-type. Distribution coefficients allowed knowing the Zn adsorption capacity of the untreated soil, and of the organic matter, oxides, and clay fraction. Soil organic matter is the main component that affects Zn adsorption as long as soil pH is near neutrality. At acid pH, the oxides are the main component that affects Zn adsorption, although to a much smaller extent than the organic matter near neutral conditions. So soil pH is the main soil factor that determines Zn adsorption, before any other soil property.
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Fenilcetonúrias , Transtornos do Sono-Vigília , Adolescente , Criança , Dopamina , Humanos , Prevalência , SerotoninaRESUMO
BACKGROUND: Alcohol consumption during pregnancy, even when moderate, implies a risk of impaired neurodevelopment, physical impairments and malformations. Its early identification is essential for establishing preventive measures to diminish disabilities among newborns. METHODS: To determine the frequency of consumption of substance use in pregnant women, we have used the techniques of gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry to detect drugs and markers of chronic consumption of alcohol in meconium. We performed a prospective study during a period of 10 months among 110 infants in our hospital, assessing anthropometry, neuromuscular development and determination of toxic substances in urine and meconium. Furthermore, meconium analysis identified fatty acid ethyl esters (FAEEs) and ethyl glucuronide (Etg). We also conducted a survey regarding the obstetric history, toxic habits, and employment status of the mothers. RESULTS: According to early detection markers analyzed in meconium (FAEE >1000 ng/g and/or Etg >50 ng/g meconium), 34.65% of pregnant women consumed alcohol during pregnancy, and 17% were positive for both markers. Within the positive cases, 50% of those exceeding a FAEE's value of 5000 ng/g in meconium had low birth-weight children. Only 5/110 mothers (4.5%) admitted to occasional alcohol consumption during pregnancy. Nobody admitted to frequent intake. The cocaine test was positive in three cases; two of them were positive for alcohol as well. CONCLUSION: As expected, many screening devices do not accurately capture use during pregnancy and supplemental methods such as meconium analysis of biomarkers of chronic alcohol consumption may be warranted.
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Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos do Espectro Alcoólico Fetal/diagnóstico , Mecônio/química , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Detecção do Abuso de Substâncias/métodos , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Biomarcadores/análise , Cromatografia Líquida , Ésteres/análise , Ácidos Graxos/análise , Feminino , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Glucuronatos/análise , Humanos , Recém-Nascido , Masculino , Idade Materna , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos Prospectivos , Espanha/epidemiologia , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
Knowledge of hyperphenylalaninemia (HPA) mutational spectrum in a population allows in many cases an accurate prediction of the phenotype and tetrahydrobiopterin (BH4) responsiveness, thus selecting an adequate treatment. In this work, we have performed the molecular characterization of 105 HPA patients from Galicia, in the northwest region of Spain, evaluating their phenotype and BH4 response. The mutational spectrum analysis showed 47 distinct mutations in 89 families, 37 of them (78.7%) corresponding to missense mutations. Six mutations account for 47.2% of all the investigated alleles, each one with a frequency ≥ 5% (IVS10-11G>A, p.R261Q, p.V388M, p.R176L, p.E280K, p.A300S). The most prevalent HPA mutations in Galicia are the common Mediterranean mutation IVS10-11G>A and p.R261Q, with frequencies of 13.8% and 10.5%, respectively. One novel mutation (p.K361Q; c.1081A>C) was also reported. Although a good genotype-phenotype correlation is observed, there is no exact correlation for some genotypes involving mutations p.R261Q, p.I65T or IVS10-11G>A. Forty seven patients were monitored for post-challenge BH4, establishing genotype-based predictions of BH4-responsiveness in all of them. All phenylketonuric patients with 2 nonresponsive mutations were unresponsive to BH4 and patients with mutations previously associated with BH4 responsiveness in the two alleles had a clear positive response to the test, with the exception of 5 patients with mutations p.R261Q, p.I65T and p.R68S. Our study supports a similar degree of heterogeneity of the HPA mutation spectrum in Galicia compared to reported data from Southern Europe. Patients carrying null mutations in both alleles showed the highest degree of concordance with the most severe phenotypes. Genotype is a good predictor of BH4 response.
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Biopterinas/análogos & derivados , Mutação , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/epidemiologia , Fenilcetonúrias/genética , Adolescente , Adulto , Biopterinas/farmacologia , Criança , Pré-Escolar , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Masculino , Epidemiologia Molecular , Linhagem , Fenilalanina Hidroxilase/deficiência , Espanha/epidemiologia , Adulto JovemRESUMO
BH4 therapy is an advancement in the treatment of phenylketonuria, reducing blood phenylalanine (phe) levels and increasing tolerance to natural proteins of responding patients. We report the results of 16 patients undergoing long-term BH4 treatment. Responding patients to BH4 was usually based on 24-h loading tests; a ≥30% decrease in blood phe was considered a positive response. Weekly loading made it possible to identify an additional "slow responder." The 16 responders constitute 24.6% of patients who completed the trial (87.5% of responders in mild hyperphenylalaninemia, 38.1% in mild PKU, and 2.8% in classical PKU).Mean dose of BH4 used was 9.75 ± 0.9 mg/kg per day, during a mean of 62 months. Age at treatment start was below 4 years in seven patients; five of which begun treatment during their first month since birth. All but one patient showed good treatment compliance; six continue on BH4 monotherapy without dietary phe restriction; six showed an increase in phe tolerance of 24-55%; and in the five patients who received treatment since the neonatal period an increase in phe tolerance following the phase of maximum growth has persisted. None of the patients showed side effects except one whom vomiting at the beginning of the treatment.Testing at the time of diagnosis in the neonatal period is very appropriate, and if there is a positive response, the patient can be treated with BH4 from onset with the advantage of being able to continue breast-feeding.
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Neonatal screening of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is of major importance due to the significant morbidity and mortality in undiagnosed patients. MCADD screening has been performed routinely in Galicia since July 2000, and until now 199,943 newborns have been screened. We identified 11 cases of MCADD, which gives an incidence of 1/18,134. During this period, no false negative screens have been detected. At diagnosis, all identified newborns were asymptomatic. Our data showed that octanoylcarnitine (C8) and C8/C10 ratio are the best markers for screening of MCADD. C8 was increased in all patients and C8/C10 was increased in all but one patient.The common mutation, c.985A > G, was found in homozygosity in seven newborns and in compound heterozygosity in three, while one patient did not carry the common mutation at all. In addition, two novel mutations c.245G > C (p.W82S) and c.542A > G (p.D181G) were identified. Ten of the 11 identified newborns did not experience any episodes of decompensation. The patient with the highest level of medium chain acylcarnitines at diagnosis, who was homozygous for the c.985A > G mutation, died at the age of 2 years due to a severe infection.This is the first report of the results from neonatal screening for MCADD in Spain. Our data provide further evidence of the benefits of MCADD screening and contribute to better understanding of this disease.
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Tyrosinemia type I is a potentially lethal disease if not diagnosed and treated properly. Diagnostic and therapeutic advances in recent years have significantly improved the prognosis for these patients. It is therefore important that the pediatrician has a clinical practice guideline with recommendations for diagnosis and treatment of this disease that leads to the appropriate intervention.