Consenso mexicano de tirosinemia tipo 1

INTRODUCTION: Tyrosinemia type 1 is a rare disease with autosomal recessive inheritance, featuring various clinical manifestations. These may encompass acute neonatal liver failure, neonatal cholestatic syndrome, chronic hepatitis, cirrhosis, hepatocellular carcinoma, and, alternatively, kidney disorders like renal tubular acidosis, Fanconi syndrome, hypophosphatemic rickets, among other alterations. Diagnosis relies on detecting toxic metabolites in the blood and urine, ideally confirmed through molecular testing. METHOD: A consensus was reached with experts in the field of inborn errors of metabolism (EIM), including eight pediatric gastroenterologists, two EIM specialists, two geneticists, three pediatric nutritionists specialized in EIM, and a pediatric surgeon specializing in transplants. Six working groups were tasked with formulating statements and justifications, and 32 statements were anonymously voted on using the Likert scale and the Delphi method. The first virtual vote achieved an 80% consensus, with the remaining 20% determined in person. RESULTS: The statements were categorized into epidemiology, clinical presentation, diagnosis, nutritional and medical treatment, and genetic counseling. CONCLUSIONS: This consensus serves as a valuable tool for primary care physicians, pediatricians, and pediatric gastroenterologists, aiding in the prompt diagnosis and treatment of this disease. Its impact on the morbidity and mortality of patients with tyrosinemia type 1 is substantial.

INTRODUCCIÓN: La tirosinemia tipo 1 es una enfermedad rara, con herencia autosómica recesiva, con múltiples manifestaciones clínicas, que pueden comprender desde falla hepática aguda neonatal, síndrome colestásico neonatal, hepatitis crónica, cirrosis o hepatocarcinoma, hasta alteraciones renales como acidosis tubular renal, síndrome de Fanconi o raquitismo hipofosfatémico, entre otras. El diagnóstico se basa en la presencia de metabolitos tóxicos en la sangre y la orina, idealmente con la confirmación molecular de la enfermedad. MÉTODO: Se realizó un consenso con expertos en el área de los errores innatos del metabolismo (EIM): ocho gastroenterólogos pediatras, dos médicos especialistas en EIM, dos genetistas, tres nutriólogas pediatras especializadas en EIM y un cirujano pediatra especialista en trasplantes. Se formaron seis mesas de trabajo encargadas de desarrollar los enunciados con sus justificaciones y fueron votados anónimamente 32 enunciados en una escala Likert con un método Delphi. La primera votación fue virtual, obteniendo consenso del 80% de los enunciados, y la segunda fue presencial, obteniendo el 20% restante. RESULTADOS: Los enunciados fueron divididos en epidemiología, cuadro clínico, diagnóstico, tratamiento nutricional y médico, y consejo genético. CONCLUSIONES: Este consenso constituye una valiosa herramienta para los médicos de atención primaria, pediatras y gastroenterólogos pediátricos, ya que ayuda a diagnosticar y tratar rápidamente esta enfermedad. Su impacto en la morbilidad y mortalidad de los pacientes con tirosinemia tipo 1 es sustancial.

Coste-efectividad del cribado neonatal de la tirosinemia tipo I (actualización) / Cost-effectiveness of newborn screening for tyrosinemia type I (update)

INTRODUCCIÓN La tirosinemia tipo I (TH1) es una enfermedad autosómica recesiva caracterizada por el déficit de la enzima fumaril acetoacetato hidrolasa. Los síntomas clínicos son variables e incluyen fallo hepático agudo, cirrosis, carcinoma hepatocelular (CHC), síndrome renal de Fanconi y neuropatía periférica. La TH1 es una enfermedad rara, de la que se calcula una frecuencia no mayor de 1 caso cada 100.000 recién nacidos vivos en la población mundial. La TH1, si no se trata, tiene pronóstico fatal, tanto en su forma aguda como crónica. Tradicionalmente el tratamiento ha consistido en una dieta con restricción de aminoácidos, fenilalanina y tirosina, y en el trasplante hepático. Actualmente existe un tratamiento farmacológico, la nitisinona, capaz de prevenir la degradación de la tirosina y la formación de metabolitos tóxicos. La introducción de la nitisinona como tratamiento de la TH1 se ha acompañado de un descenso considerable de la tasa de mortalidad. Actualmente, en España la TH1 no está incluida dentro del programa de cribado neonatal (PCN) de la cartera común de servicios del SNS. OBJETIVOS Evaluar y actualizar el coste-efectividad de la inclusión de la detección precoz de la TH1 mediante MS/MS en un PCN. • Estimar el impacto presupuestario que supondría para el SNS la inclusión de la detección precoz de la TH1 mediante MS/MS en el PCN actual. METODOLOGÍA Se realizó una revisión sistemática de la evidencia científica sobre el coste-efectividad del cribado neonatal de la TH1 para lo que se elaboró una estrategia de búsqueda en las bases de datos electrónicas: MEDLINE, EMBASE, Web of Science (WOS) y Cochrane desde 2013 hasta abril de 2021. Se ha desarrollado un modelo de coste-efectividad que compara dos alternativas: implantar el cribado neonatal de la tirosinemia tipo I o realizar la detección clínica de esta enfermedad. La perspectiva del análisis fue la del SNS, teniendo en cuenta los costes directos, expresados en euros de 2021. De manera adicional se tiene en cuenta la perspectiva social incluyendo los costes debidos a posibles pérdidas de productividad. La efectividad se midió empleando la medida Años de Vida Ajustados por Calidad (AVAC). Tanto los costes como la efectividad se descontaron al 3%. Por último, se realizó un análisis de impacto presupuestario para informar del coste que supondría la inclusión de la TH1 en el PCN del SNS. RESULTADOS Revisión sistemática de coste-efectividad Únicamente se pudo considerar un informe del Institute of Health Economics de Alberta (Canadá), localizado mediante búsqueda manual, publicado en 2016; cuyo objetivo fue evaluar la efectividad, seguridad y coste-efectividad de añadir siete condiciones al programa de cribado neonatal canadiense (incluyendo la TH1), mediante modelización tipo Markov. La calidad metodológica de la evaluación económica es alta. La perspectiva empleada es la del tercer pagador incluyendo exclusivamente los costes directos sanitarios; informando de un coste por niño cribado de 28,40 $CAD (21,20 € de 2021) frente a los 26,50 $CAD (19,78 € de 2021) por niño no cribado. La diferencia en años de vida entre ambas estrategias es de 0,00006 lo que resulta en una RCEI de 31.723,53 $CAD/AV (aproximadamente 23.666,66 €/AV en 2021). Aunque los autores no hacen mención al umbral coste-efectividad de referencia (y, por tanto, no especifican si la alternativa se considera coste-efectiva o no), declaran que, dado que la detección de una sola afección o una combinación de ellas produce un beneficio adicional para la salud, con costes adicionales para el sistema, su adopción depende de la disponibilidad de fondos. Análisis económico El análisis coste-efectividad muestra que el coste promedio por niño no cribado asciende a 33,03 €, mientras que el coste por niño cribado es de 35 €. Tanto los AVG como los AVAC promedio son más elevados con la estrategia de cribado neonatal lo que resulta en una RCEI de 30.034,32 €/AVAC desde la perspectiva del SNS y de 28.017,90 €/AVAC desde la perspectiva social. Ambos valores se encuentran por encima pero cercanos al umbral de coste-efectividad estimado para España en 25.000 €/AVAC. Al analizar diferentes escenarios variando los parámetros sobre los que existe mayor incertidumbre, se obtiene que la incorporación de la TH1 al programa de cribado neonatal sería una alternativa coste-efectiva si el precio del reactivo adicional para la detección de la TH1 mediante MS/MS no supera los 0,20 €/reactivo. El análisis de impacto presupuestario muestra que el coste incremental por niño cribado en el primer año se sitúa en torno a los 0,37 €, que equivale a 123.801 € para el conjunto de neonatos nacidos en España. CONCLUSIONES Existe muy escasa evidencia en la literatura científica sobre el coste-efectividad de un programa de cribado neonatal de la TH1 mediante MS/MS. Sólo se ha localizado un informe de ETS que concluye que la incorporación de la TH1 a un programa de cribado neonatal debe valorarse en función de la disponibilidad presupuestaria. • El análisis de coste-efectividad de novo realizado en este informe con datos actualizados de España concluye que la implantación del cribado neonatal de la TH1 no sería una opción coste-efectiva desde la perspectiva del SNS, ni desde la perspectiva social teniendo en cuenta una DAP de 25.000 €/AVAC. Sin embargo, si el coste del reactivo adicional necesario para la detección de la TH1 mediante MS/MS no supera los 0,20 €/reactivo, la inclusión de esta enfermedad dentro del programa de cribado neonatal mediante MS/MS sí sería una alternativa coste-efectiva. • De acuerdo al análisis de impacto presupuestario, cribar la TH1 tendría un coste incremental por neonato bajo, de aproximadamente 0,37 € el primer año.

INTRODUCTION Tyrosinemia type I (TH1) is an autosomal recessive disease characterized by a deficiency of the enzyme fumaril acetoacetate hydrolase. Clinical symptoms are variable and include acute liver failure, cirrhosis, hepatocellular carcinoma (HCC), Fanconi renal syndrome, and peripheral neuropathy. TH1 is a rare disease, with an estimated frequency of not more than 1 case per 100,000 live newborns in the world population. If untreated, TH1 has a fatal prognosis, both in its acute and chronic forms. Traditionally, treatment has consisted of a diet with restriction of amino acids, phenylalanine and tyrosine, and liver transplantation. Currently there is a pharmacological treatment, nitisinone, capable of preventing the degradation of tyrosine and the formation of toxic metabolites. The introduction of nitisinone as a treatment for TH1 has been accompanied by a considerable decrease in the mortality rate. Currently, in Spain TH1 is not included in the newborn screening programme of the portfolio of common services of the National Health System (NHS). OBJECTIVES To evaluate the cost-effectiveness of newborn screening for TH1. • To determine the cost-effectiveness of including early detection of TH1 by MS/MS in a newborn screening programme. • To estimate the budget impact of implementation of early detection of TH1 through MS/MS in NHS. METHODS A systematic review of the scientific evidence on the cost-effectiveness of newborn screening for TH1 was carried out, for which a search strategy was developed in electronic databases: MEDLINE, EMBASE, Web of Science (WOS) and Cochrane since 2013 until April 2021. A cost-effectiveness model has been developed that compares two alternatives: implement newborn screening for type I tyrosinemia or carry out clinical detection of this disease. The perspective of the analysis was that of the SNS, taking into account direct healthcare costs, expressed in 2021 euros. Effectiveness was measured using the Quality-Adjusted Life Years (QALY) measure. Both costs and effectiveness were discounted at 3%. Finally, a budget impact analysis was carried out to report the cost of including newborn screening of TH1 in the NHS. RESULTS Cost-effectiveness systematic review Only a HTA-report from the Institute of Health Economics of Alberta (Canada), located by manual search and published in 2016, could be considered. The objective of this report was to evaluate the effectiveness, safety and cost-effectiveness of adding seven conditions (including TH1), to the Canadian newborn screening program using Markov-type modeling. The methodological quality of the economic evaluation was high. The perspective used is that of the third payer, including exclusively direct healthcare costs. The authors reported a cost per child screened of CAD $ 28.40 (€ 21.20 from 2021) compared to CAD $ 26.50 (€ 19.78 from 2021) per child not screened. The difference in life years between both strategies is 0.00006, which results in an ICER of CAD $ 31,723.53/LYs (approximately € 23,666.66/LYs in 2021). Although the authors do not mention a country willigness to pay (WTP) reference (and, therefore, do not specify whether the alternative is considered cost-effective or not), they declare that, since the detection of a single condition or a combination of them produces an additional benefit for health with additional costs for the system, its adoption depends on the availability of funds. Economic analysis The cost-effectiveness analysis shows that the mean cost per child not screened is € 33.03, while the cost per child screened is € 35. Both the LYs and QALYs are higher with the newborn screening strategy, which results in an ICER of 30,034.32 €/QALY from the NHS perspective and 28,017.90 €/LY from societal perspective. Both values are close to the cost-effectiveness threshold estimated for Spain at €25,000/QALY. When analyzing different scenarios varying the parameters about which there is greater uncertainty, it is obtained that the incorporation of TH1 to the neonatal screening program would be a cost-effective alternative if the price of the additional reagent used for the detection of TH1 by MS/MS does not exceeds €0.20/reagent. The budget impact analysis shows that the incremental cost per child screened in the first year is around € 0.37, which is equivalent to € 123,801 for all newborns born in Spain. CONCLUSIONS There is limited scientific literature evidence on the cost effectiveness of TH1 newborn screening using MS/MS. Only one HTA report has been located that concludes that the incorporation of TH1 into a newborn screening program should be assessed based on budget availability. • The cost-effectiveness analysis carried out in this report with updated data from Spain concludes that the implementation of TH1 newborn screening would be a cost-effective option from the NHS perspective if the price of the reagent used to detect the disease does not exceed €0.20/reagent. • According to the budget impact analysis, screening TH1 would have a low incremental cost per newborn, of approximately € 0.37 the first year.

Case report: Maternal tyrosinemia type 1a under NTBC treatment with tyrosine- and phenylalanine restricted diet in Chile.

We report the case of a 17-year-old girl with Tyrosinemia type 1a who carried a planned pregnancy to term while being under 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC, nitisinone) treatment and a tyrosine- and phenylalanine-restricted diet. She was on treatment since 2 months of age with poor metabolic control prior to her pregnancy (tyrosine 838 ± 106 umol/L). NTBC and a low tyrosine and phenylalanine diet were continued during her pregnancy. She unfortunately suffered from urinary tract infection and anemia during her pregnancy, with median plasma tyrosine and phenylalanine levels of 613 ± 106 umol/L (200-400 umol/L) and 40.2 ± 8 umol/L (35-90 umol/L), respectively. After 40 weeks of gestation, the patient gave birth to a healthy boy, with no adverse effects related to the use of NTBC. The newborn presented with a transitory elevation of plasma tyrosine levels and normal phenylalanine, methionine, and succinylacetone levels. By 12 months of age, the child was determined to have normal psychomotor development. At 20 months old, he was diagnosed with a mild developmental delay; however, global cognitive evaluation with the Wechsler Intelligence Scale for Children (WISC) test at 5 years old showed normal performance. Here, we discuss one of the few reported cases of nitisinone treatment during pregnancy and demonstrate a lack of teratogenicity and long-term cognitive disabilities.

TYROSINEMIA TYPE III: A CASE REPORT OF SIBLINGS AND LITERATURE REVIEW.

OBJECTIVE: Tyrosinemia type III (HT III) is the rarest form of tyrosinemia, and the full clinical spectrum of this disorder is still unknown. The neurological involvement varies, including intellectual impairment and attention deficit disorder with hyperactivity (ADHD). We report the case of two siblings diagnosed with HT III at different ages. CASE DESCRIPTION: The index case was diagnosed by newborn screening for endocrine and metabolic disorders, starting a low-protein diet immediately, with a consistent decrease in tyrosine levels. By the age of three, the child displayed a hyperactive behavior, starting treatment for ADHD two years later. At seven years of age, he shows a slight improvement in terms of behavior and attention span and has a cognitive performance slightly lower than his peers, despite maintaining acceptable tyrosine levels. His sister, who had a history of ADHD since age five, was diagnosed with HT III after family screening at the age of eight. Despite initiating a dietetic treatment, her behavior did not improve, and she has a mild intellectual impairment. COMMENTS: This is the first case report describing siblings with HT III who underwent nutritional treatment with a low-protein diet in different phases of life, with a better neurological and behavioral evaluation in the patient who started treatment earlier.

Tyrosinemia type iii: a case report of siblings and literature review / Tirosinemia tipo iii: descrição de caso clínico em irmãos e revisão da literatura

ABSTRACT Objective: Tyrosinemia type III (HT III) is the rarest form of tyrosinemia, and the full clinical spectrum of this disorder is still unknown. The neurological involvement varies, including intellectual impairment and attention deficit disorder with hyperactivity (ADHD). We report the case of two siblings diagnosed with HT III at different ages. Case description: The index case was diagnosed by newborn screening for endocrine and metabolic disorders, starting a low-protein diet immediately, with a consistent decrease in tyrosine levels. By the age of three, the child displayed a hyperactive behavior, starting treatment for ADHD two years later. At seven years of age, he shows a slight improvement in terms of behavior and attention span and has a cognitive performance slightly lower than his peers, despite maintaining acceptable tyrosine levels. His sister, who had a history of ADHD since age five, was diagnosed with HT III after family screening at the age of eight. Despite initiating a dietetic treatment, her behavior did not improve, and she has a mild intellectual impairment. Comments: This is the first case report describing siblings with HT III who underwent nutritional treatment with a low-protein diet in different phases of life, with a better neurological and behavioral evaluation in the patient who started treatment earlier.

RESUMO Objetivo: A tirosinemia tipo III (TT III) é a forma mais rara das tirosinemias e o espectro clínico desta entidade não está totalmente esclarecido. O envolvimento neurológico é variável, incluindo o atraso cognitivo ou transtorno do déficit de atenção com hiperatividade (TDAH). Descrevemos o caso de dois irmãos que foram diagnosticados com TT III em idades diferentes. Descrição dos casos: O caso índice foi diagnosticado no contexto do rastreio endócrino-metabólico neonatal, tendo iniciado imediatamente dieta hipoproteica, com redução consistente dos níveis de tirosina. Por volta dos três anos, foi detectado um comportamento hiperativo, tendo iniciado dois anos depois tratamento para o TDAH. Aos sete anos, apresenta leve melhora de comportamento e da atenção e avaliação cognitiva levemente inferior ou pouco abaixo quando comparado a crianças da mesma faixa etária, apesar de manter níveis aceitáveis de tirosina. A sua irmã, com história de TDAH desde os cinco anos, foi diagnosticada de TT III aos oito anos no contexto do rastreio de familiares. Apesar de iniciar tratamento dietético, nenhum efeito foi notado em termos de comportamento e a doente apresenta leve atraso cognitivo. Comentários: Este é o primeiro caso clínico descrito de irmãos com TT III que iniciaram terapêutica dietética com dieta hipoproteica em diferentes fases da vida, com melhor avaliação em termos neurológicos e comportamentais no doente que iniciou tratamento mais precocemente.

Hepatorenal Tyrosinemia in Mexico: A Call to Action.

Hepatorenal tyrosinemia is a treatable metabolic disease characterized by progressive liver failure, renal damage and pronounced coagulopathy. Its clinical diagnosis is difficult because of its low prevalence and heterogeneous symptoms. In developed countries, expanded newborn screening, based on succinylacetone quantification by tandem mass spectrometry, has been very valuable in the early detection of hepatorenal tyrosinemia, providing the opportunity for rapid treatment of affected patients. In developing countries without systematic expanded newborn screening, however, diagnosis and treatment of this disease remain major challenges, as genetic diseases in these countries are not a health priority and there are few referral centers for infants with inherited errors of metabolism. This chapter describes the diagnosis, follow-up and outcome of 20 Mexican patients with hepatorenal tyrosinemia. This chapter also constitutes a call to action to pediatricians, gastroenterologists, geneticists and other health professionals, and to academic organizations, health authorities and patient advocacy groups, to promote early patient detection and treatment, reducing the unacceptably high mortality rate (75%) in Mexican infants with this potentially deadly but eminently treatable condition.

Herpetiform keratitis and palmoplantar hyperkeratosis: warning signs for Richner-Hanhart syndrome

Richner-Hanhart syndrome (RHS, tyrosinemia type II) is a rare, autosomal recessive inborn error of tyrosine metabolism caused by tyrosine aminotransferase deficiency. It is characterized by photophobia due to keratitis, painful palmoplantar hyperkeratosis, variable mental retardation, and elevated serum tyrosine levels. Patients are often misdiagnosed with herpes simplex keratitis. We report on a a boy from Brazil who presented with bilateral keratitis secondary to RHS, which had earlier been misdiagnosed as herpes simplex keratitis

Herpetiform keratitis and palmoplantar hyperkeratosis: warning signs for Richner-Hanhart syndrome.

Richner-Hanhart syndrome (RHS, tyrosinemia type II) is a rare, autosomal recessive inborn error of tyrosine metabolism caused by tyrosine aminotransferase deficiency. It is characterized by photophobia due to keratitis, painful palmoplantar hyperkeratosis, variable mental retardation, and elevated serum tyrosine levels. Patients are often misdiagnosed with herpes simplex keratitis. We report on a a boy from Brazil who presented with bilateral keratitis secondary to RHS, which had earlier been misdiagnosed as herpes simplex keratitis.

Tyrosinemia type I: clinical and biochemical analysis of patients in Mexico.

INTRODUCTION: Hepatorenal tyrosinemia (HT1) is a treatable, inherited, metabolic disease characterized by progressive liver failure with pronounced coagulopathy. The aim of this study is to describe the clinical, biochemical, and histopathological findings in a group of Mexican HT1 patients and their outcome. MATERIAL AND METHODS: Medical records of HT1 patients diagnosed between 1995 and 2011 were analyzed. The diagnosis of HT1 was confirmed by detection of succinylacetone in urine or blood. RESULTS: Sixteen nonrelated HT1 cases were analyzed. Mean age at clinical onset was 9 months, and the mean age at diagnosis was 16.3 months. Main clinical findings were hepatomegaly, splenomegaly, cirrhosis, liver failure, tubulopathy, nephromegaly, Fanconi syndrome, seizures and failure to thrive. Histopathological findings were cirrhosis, fibrosis and steatosis. The HT1 group had a mortality rate of 78%. Patients who received supportive care or nutritional treatment had a 3-year survival rate of 10%. For those who underwent liver transplantation, the 6-year survival rate was 60%. In most cases pharmacological treatment with nitisinone and special dietary products were not available. The leading causes of death were fulminant liver failure, metastatic hepatocellular carcinoma, and porphyria-like neurologic crisis. Newborn screening programs in combination with the availability of orphan drugs, proper monitoring, genetic counseling, and clinical practice guidelines are needed to enable physicians to identify the disease, delay its progression, and improve patients' quality of life. CONCLUSION: The devastating natural history of HT1 is still observed in Mexican patients because they are not diagnosed and treated during the early stages of the disease.

Crisis neurológica en Tirosinemia hereditaria / Neurological crisis in hereditary Tyrosinaemia

La Tirosinemia tipo I es el resultado de un error innato en la etapa final del metabolismo de la Tirosina. Sus manifestaciones clínicas son variables, las cuales pueden verse agravadas con la aparición de crisis neurológica. El objetivo del presente trabajo es reportar el caso de una preescolar portadora de la enfermedad, que desarrolló parálisis fláccida asociada a insuficiencia respiratoria y que requirió conexión a ventilación mecánica.

Cirrosis hepatiaa en lactante: una forma de presentacion de la tiroinnemia / Hepatic circosis in infant: a form of presentation of thyrosynemia

We present two documented cases of patients with Tyrosinemia type I (Hepatorenal Tyrosinemia) in infants. The most constant imaging findings in target organs: Liver (Hepatic Cirrhosis), Kidneys (Nefromegaly) are described and compared with pathological findings in one case. In the presence of confusing clinical manifestations, radiological findings of hepatic cirrhosis in infants associated with renal involvement are almost diagnostic of this entity.

Se presentan 2 casos documentados de lactantes portadores de Tirosinemia tipo I (Hepatorenal). Se describen los hallazgos imagenológicos principales de ella en los órganos blanco: Hígado (Cirrosis Hepática) y riñones (Nefromegalia) y se confrontan con los de la anatomía patológica en un caso. En un lactante, con un cuadro clínico poco claro, el hallazgo imagenológico de cirrosis hepática sumado a un compromiso renal, deben hacer plantear el diagnóstico de tirosinemia.

[Diagnostic error of mental retardation of neurometabolic origin confirmed by mass sequential spectrometry]. / Error diagnóstico de retraso mental de origen neurometabólico confirmado por espectrometría de masa secuencial.

INTRODUCTION: The metabolic screening test gives the first laboratory indication for neurometabolic alterations which can cause mental retardation. Some techniques such as thin layer chromatography, are still used in several countries to confirm the diagnosis of inborn errors of metabolism after a general screening test. PATIENTS AND METHODS: Two patients from a mentally retarded Colombian population were reported positive for the Nitrosonaphtol test, and remained positive to tyrosine metabolism alteration by thin layer chromatography, suggesting the correspondent management. In the present study we tried to confirm the last diagnosis, performing tandem mass spectrometry analysis of acylcarnitines and amino acids, on blood samples of all patients from the last study, which were found negative for any alteration. CONCLUSION: Is necessary to improve the diagnosis methods used in some countries in order to avoid mistakes that can change the life-style of the wrongly diagnosed patients.

Persistent tyrosinemia detected by thin-layer chromatography.

Screening for tyrosinemia is not routinely performed worldwide. Using a low expense thin-layer chromatography (TLC) for amino acids we detected a high frequency of transient tyrosinemia with secondary hyperphenylalaninemia in some newborns. Serum follow up showed the need to introduce adequate therapy in these babies.