RESUMO
Fumaric aciduria resulting from fumarate hydratase deficiency is a rare inherited disorder of the Krebs tricarboxylic acid cycle that is characterized by neurologic manifestations, a spectrum of brain abnormalities, and the excretion of fumaric acid in urine. We describe a 3 year old Sri Lankan boy who was referred at age 10 months with poor weight gain and hypotonia for further laboratory investigations. In addition to global developmental delay, there were noticeable dysmorphic features with a prominent forehead, low-set ears, micrognathia, and hypertelorism with persistent neutropenia. Urine organic acid assay revealed a massive elevation of fumaric acid on 2 occasions. Molecular analysis revealed a homozygous likely pathogenic missense variant, NM000143.3:c.1048C>T p. (Arg350Trp), in the FH gene, confirming the biochemical diagnosis. Our patient was the first patient in Sri Lanka molecularly diagnosed with fumaric aciduria. This case study highlights the importance of performing organic acid assays in children presenting with neurologic manifestations especially when these are suspected to have a metabolic basis.
Assuntos
Testes Diagnósticos de Rotina , Hipotonia Muscular , Criança , Pré-Escolar , Fumarato Hidratase/deficiência , Fumarato Hidratase/genética , Fumarato Hidratase/metabolismo , Humanos , Lactente , Masculino , Erros Inatos do Metabolismo , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/genética , Transtornos Psicomotores , Sri LankaRESUMO
BACKGROUND: Dubin-Johnson syndrome and intrahepatic cholestasis of pregnancy are rare chronic liver disorders. Dubin-Johnson syndrome may manifest as conjugated hyperbilirubinemia, darkly pigmented liver, presence of abnormal pigment in the parenchyma of hepatocytes and abnormal distribution of the coproporphyrin isomers I and III in the urine. Intrahepatic cholestatic jaundice of pregnancy presents as pruritus, abnormal liver biochemistry and increased serum bile acids. CASE PRESENTATION: A Sri Lankan girl presented with recurrent episodes of jaundice. She had conjugated hyperbilirubinaemia with diffuse, coarse brown pigments in the hepatocytes. Urine coproporphyrin examination suggested Dubin-Johnson syndrome. Genetic studies confirmed missense homozygous variant p.Trp709Arg in the ATP-binding cassette sub-family C member 2 gene ABCC2 that encodes the Multidrug resistance-associated protein 2 that causes Dubin-Johnson syndrome. The gene study of the mother revealed the same missense variant in ABCC2/MRP2 but with a heterozygous status, and in addition a homozygous missense variant p.Val444Ala in the ATP-binding cassette, sub-family B member 11 gene ABCB11 that encodes the bile salt export pump. CONCLUSION: Dubin-Johnson syndrome should be considered when the common causes for conjugated hyperbilirubinaemia have been excluded, and patient has an increased percentage of direct bilirubin relative to total bilirubin concentration. Its early diagnosis prevents repeated hospital admissions and investigations. Knowledge of a well known homozygous variant in ABCB11 gene could help in the management of pregnancy.
Assuntos
Colestase Intra-Hepática/complicações , Icterícia Idiopática Crônica/complicações , Sequência de Bases , Biópsia , Pré-Escolar , Colestase Intra-Hepática/genética , Éxons/genética , Família , Feminino , Hepatócitos/patologia , Humanos , Icterícia Idiopática Crônica/genética , Fígado/patologia , Proteína 2 Associada à Farmacorresistência Múltipla , Complicações na Gravidez/genética , Análise de Sequência de DNA , Sri LankaRESUMO
Following publication of the original article [1], the authors requested the following corrections: 1. Author 2-given name should be Dilanthi and family name Warawitage. 2. Author 6-given name should be Nalika and family name de Silva.