Tirosinemia de tipo 1 en un lactante / Type 1 Tyrosinemia in an infant

Se describe el caso clínico de una paciente de 2 meses de edad, quien nació a término y normopeso; se alimentaba con lactancia materna exclusiva y tuvo antecedente de 2 ingresos previos (anemia severa y catarro común). Fue hospitalizada en el Servicio de Terapia Intensiva del Hospital Infantil Sur Dr Antonio María Béguez César por presentar edemas generalizados y ascitis, con evolución rápida hacia un cuadro de insuficiencia hepática aguda. Las pruebas metabólicas de orina y sangre permitieron confirmar el diagnóstico de tirosinemia de tipo 1. A pesar de brindarle la atención requerida, la paciente evolucionó desfavorablemente.

The case report of a 2 months of age patient is described who was born at term and normal in weight; she fed with exclusive breast feeding and she had a history of 2 previous admissions (severe anemia and common cold). She was hospitalized in the Intensive Therapy Service of Dr Antonio María Béguez Caesar Southern Pediatric Hospital due to widespread edemas and ascites, with a fast clinical course to an acute liver failure. The metabolic tests of urine and blood allowed to confirm the diagnosis of type 1 tyrosinemia. In spite of offering her the required care, the patient had an unfavourable clinical course.

Cirrosis Hepática como forma de presentación de Tirosinemia tipo 1

La tirosinemia hereditaria tipo I (THI) o tirosinemia hepato-renal es una enfermedad autosómica recesiva causada por la deficiencia del enzima fumarilacetoacetato hidrolasa, que tiene lugar en el citosol de las células hepática, a consecuencia del bloqueo se forma succinilacetona, que es el metabolito que permite confirmar este diagnóstico. Además, presentan elevación de tirosina y de metionina en sangre y orina. Con un cuadro clínico variable, se puede manifestar desde una forma neonatal grave hasta una presentación asintomática tardía o crónica. El diagnóstico rápido y el manejo nutricional son importantes para la evolución. Se presentan caso, confirmado como tirosinemia I forma crónica

Inherited tyrosinemia type I (THI) or hepato-renal tyrosinemia is an autosomal recessive disease caused by the deficiency of the enzyme fumarylacetoacetate hydrolase, that occurs in the liver cell cytosol; as a result of this deficiency, succinylacetone is formed, which is the metabolite that confirms the diagnosis. In addition, they have elevated tyrosine and methionine in blood and urine. With a variable clinical picture, it can manifest itself from a severe neonatal form until late or chronic asymptomatic presentation. Rapid diagnosis and nutritional management are important for evolution. The case presented is confirmed as chronic tyrosinemia I

Estresse oxidativo em porfiria hepâtica experimental disparadapor succinilacetona - urn inibidor da âcido 5-aminolevulinico desidratase / Oxidative stress in experimental hepatic porphyria triggered bysuccinylacetone — an inhibitor of 5-aminoluvulinic acid dehydratase

Para otimizar urn modelo experimental para o estudo do desbalanço redox em porfirias relacionadas ao acúmulo de ácido 5-aminolevulinico-(ALA), via inibição da ALA desidratase-(ALA-D), ratos foram tratados com o éster metílico de succinilacetona-(SAME), um catabólito da tirosina que inibe fortemente a ALA-D, mimetizando o estado metabólico observado nos portadores de porfirias e tirosinemias. Estabeleceram-se modelos de tratamento agudo por 36 e 18 h. No primeiro, os animais receberam 3 injeções de SAME (10, 40 ou 80 mg/kg, grupos All-IV). No segundo, os animais receberam 3 injeções de 40 mg/kg de SAME, ALA ou éster metílico de ALA (grupos BII-IV), ALA:SAME (30:10 mg/kg, grupo BV), ou 10 mg/kg SAME (grupo BVI). Paralelamente, avaliou-se se os sintomas neurológicos característicos das porfirias decorriam de danos oxidativos mitocondriais. Para isso, aplicou-se uma tecnologia óptica para medidas da difusão da depressão cortical que determinou a oxigenação e o estado redox do cit c em mitocôndrias do córtex cerebral de ratos submetidos ao tratamento crônico com ALA (40 mg/kg), SAME (10 e 40 mg/kg) e ALA:SAME (30:10 mg/kg), a cada 48 h, durante 30 dias. Tratamento agudo/36 h: Os níveis de ALA no plasma, fígado, cérebro e urina e o clearance renal do ALA aumentaram nos grupos tratados. A atividade de ALA-D e a coproporfirina urinaria reduziram. A marcação para proteínas carboniladas, ferro e ferritina aumentou no fígado e cérebro dos grupos tratados, especialmente no All. Os níveis de malondialdeído hepática aumentaram no grupo AIV. A razão GSH/GSH+GSSG e a atividade de GPx cerebrais aumentaram nos grupos AIV e AIII, respectivamente. Consistentemente com estes dados indicando um desbalanço oxidativo induzido pelo SAME, alterações mitocondriais e citosólicas ultraestruturais foram reveladas, especialmente no fígado./Tratamento agudo/18 h: Os níveis de ALA plasmáticos aumentaram nos grupos tratados, exceto em BIV. 0 grupo Bll mostrou aumento dos níveis hepáticos...

To optimize an experimental model for studying redox imbalance in porphyrias related to 5-aminolevulinic acid (ALA) accumulation through the inhibition of ALA dehydratase (ALA-D), rats were treated with methyl ester of succinylacetone (SAME), a tyrosine catabolite that strongly inhibits ALA-D, what mimics the metabolic state observed in patients suffering from porphyrias and tyrosinemias. Models of acute treatment were established during 36 and 18 h. In the first model, animals received 3 injections of SAME (10, 40 or 80 mg/kg, groups All-IV). In the second model, animals received 3 injections of 40 mg/kg SAME, ALA or methyl ester of ALA (groups BII-IV), ALA:SAME (30:10 mg/kg, group BV), or 10 mg/kg SAME (group BVI). Concomitantly, we evaluated if the neurologic symptoms characteristics of porphyrias were a consequence of the oxidative mitochondria! impairment. For this, an optical technology for the measurement of cortical spreading depression was applied. This techonology determined the cerebral oxygenation and the redox state of cit c in mitochondria of the cerebral cortex of rats submitted to a chronic treatment with ALA (40 mg/kg), SAME (10 and 40 mg/kg) and ALA:SAME (30:10 mg/kg), alternate days, during 30 days. Acute treatment/36 h: ALA levels in plasma, liver and urine and clearance of renal ALA increased in treated groups. ALA-D activities and urinary coproporphyrin were found to be decreased. Liver and brain proteins carbonyl, iron and ferritin were higher in the liver of treated groups, especially in All. Liver j malondialdehyde levels were higher in group AIV. Cerebral GSH/GSH+GSSG ratio and GPx activities increased in groups AIV and AIII, respectively. Consistently with these data indicating SAME-induced oxidative imbalance, mitochondrial and cytosolic ultrastructural changes were revealed, especially in the liver. Acute treatment/18 h: Plasma ALA levels increased in all treated groups but BIV. Group BII showed increased hepatic ALA levels…

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.

Tirosinemia neonatal / Neonatal tyrosinemia

Mediante la técnica de Udenfriend y Cooper, se midieron los niveles de tirosina en la sangre del cordón de 26 prematuros y 31 niños de término, con el fin de comparar las concentraciones según la edad gestacional y detectar la presencia de la tirosinemia neonatal. Se encontró un caso de esta entidad en un niño de 31 semanas de edad gestacional, lo cual correspondió al 3.8 por ciento de los prematuros y al 1.8 por ciento del grupo total. La concentración de tirosina en el paciente fue de 53 microM. El promedio de las concentraciones en los prematuros menores de 32 semanas fue de 16.8 más o menos 6.3 microM; el de los niños entre 33 y 36 semanas fue de 19.3 más o menos 7.6 microM y el de los niños de término, de 17.2 más o menos 9.4 microM. Las pruebas estadísticas no mostraron tendencias ni diferencias significativas entre estas concentraciones. El promedio ponderado para el grupo total fue 17.7 más o menos 7.3 microM. Se recomienda establecer programas de tamizaje para detectar este problema porque puede presentar repercusiones neurológicas posteriores

By means of the Udenfriend-Cooper technique, levels of tyrosine were measured in the cord blood of 26 preterm and 31 term Infants; the objective was to compare tyrosine concentrations according to gestational age and to detect the presence of neonatal tyrosinemia. A case of this disease was found In an Infant with 31 weeks of gestational age; this case represented 3.8% of preterm Infants and 1.8% of the total group. Average tyrosine concentration according to age was as follows: 16.8: ± 6.3 µM in Infants under 32 weeks of gestational age; 19.3: ±: 7.6 µM In those between 33 and 36 weeks and 17.2 : ±: 9.4 µM In the term Infants. Statistic analyses revealed no significant trend or difference between these figures. Average concentration for the total group was 17.7 : ±: 7.3 µM. We recommend the establishment of screening programs for the detection of this disorder since It may later lead to neurological complications