RESUMO
We describe a male patient with a Y202H ornithine transcarbamylase deficiency gene mutation who had pancreatitis while taking a low-protein diet, citrulline, and sodium phenylbutyrate.
Assuntos
Doença da Deficiência de Ornitina Carbomoiltransferase/complicações , Doença da Deficiência de Ornitina Carbomoiltransferase/genética , Pancreatite/etiologia , Adolescente , Amilases/sangue , Doença Crônica , Citrulina/uso terapêutico , Terapia Combinada , Dieta com Restrição de Proteínas/efeitos adversos , Nutrição Enteral/efeitos adversos , Gastrostomia/efeitos adversos , Humanos , Lipase/sangue , Masculino , Mutação/genética , Doença da Deficiência de Ornitina Carbomoiltransferase/diagnóstico , Doença da Deficiência de Ornitina Carbomoiltransferase/terapia , Pancreatite/sangue , Pancreatite/enzimologia , Fenótipo , Fatores de RiscoRESUMO
Rothmund-Thomson syndrome is an autosomal recessive disorder characterized by poikilodermatous skin changes that develop in infancy. Associated manifestations include juvenile cataracts, sparse hair, short stature, skeletal defects, dystrophic nails and teeth, and hypogonadism. An increased incidence of malignancy, including osteosarcoma, has been reported in patients with Rothmund-Thomson syndrome. The molecular basis of the disorder is not known. This report describes a patient with Rothmund-Thomson syndrome in whom two primary osteosarcomas developed 12 years apart. The presentation, diagnosis, and treatment of osteosarcoma in this patient with Rothmund-Thomson syndrome are described. Cytogenetic and molecular analysis of peripheral blood and skin fibroblasts had low level mosaicism for trisomy of chromosomes 2 and 8. Although several patients have been described with mosaic trisomy 8 and i(2q) (mosaic isochromosome for the long arm of chromosome 2), the patient described here is the first to have mosaic trisomy for the entire chromosomes 2 and 8. The cytogenetic findings in this patient are consistent with an underlying defect in chromosomal stability.
Assuntos
Neoplasias Ósseas/complicações , Neoplasias Femorais/complicações , Úmero , Neoplasias Primárias Múltiplas , Osteossarcoma/complicações , Síndrome de Rothmund-Thomson/complicações , Neoplasias Ósseas/patologia , Criança , Cromossomos Humanos Par 2/genética , Cromossomos Humanos Par 8/genética , Humanos , Cariotipagem , Imageamento por Ressonância Magnética , Masculino , Mosaicismo , Osteossarcoma/patologia , Síndrome de Rothmund-Thomson/genéticaRESUMO
Tyrosinaemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often complicated by hepatocellular carcinoma, in childhood or early adolescence. We studied a 37-year-old woman with tyrosinaemia I whose severe liver disease in infancy and rickets during childhood resolved with dietary therapy. From 14 years of age she resumed an unrestricted diet with the continued presence of the biochemical features of tyrosinaemia, yet maintained normal liver function. In adult years she accumulated only small amounts of succinylacetone. Despite this evolution to a mild biochemical and clinical phenotype, she eventually developed hepatocellular carcinoma. Her fumarylacetoacetate hydrolase genotype consists of a splice mutation, IVS6-1g>t, and a novel missense mutation, Q279R. Studies of resected liver demonstrated the absence of hydrolytic activity and of immunological expression of fumarylacetoacetate hydrolase in liver tumour. In nontumoral areas, however, 53% of normal hydrolytic activity and immunologically present fumarylacetoacetate hydrolase was found. This case demonstrates the high risk of liver cancer in tyrosinaemia I even in a seemingly favourable biological environment.
