RESUMO
Lysosomal acid lipase (LAL) deficiency is an under-recognized lysosomal disease caused by deficient enzymatic activity of LAL. In this report we describe two affected female Mexican siblings with early hepatic complications. At two months of age, the first sibling presented with alternating episodes of diarrhea and constipation, and later with hepatomegaly, elevated transaminases, high levels of total and low-density lipoprotein cholesterol, and low levels of high-density lipoprotein. Portal hypertension and grade 2 esophageal varices were detected at four years of age. The second sibling presented with hepatomegaly, elevated transaminases and mildly elevated low-density lipoprotein and low high-density lipoprotein at six months of age. LAL activity was deficient in both patients. Sequencing of LIPA revealed two previously unreported heterozygous mutations in exon 4: c.253C>A and c.294C>G. These cases highlight the clinical continuum between the so-called Wolman disease and cholesteryl ester storage disease, and underscore that LAL deficiency represents a single disease with a degree of clinical heterogeneity.
Assuntos
Mutação , Irmãos , Esterol Esterase/deficiência , Esterol Esterase/genética , Doença de Wolman/genética , Biópsia , Criança , Pré-Escolar , Análise Mutacional de DNA , Progressão da Doença , Varizes Esofágicas e Gástricas/enzimologia , Varizes Esofágicas e Gástricas/genética , Esofagoscopia , Éxons , Fígado Gorduroso/enzimologia , Fígado Gorduroso/genética , Feminino , Predisposição Genética para Doença , Hepatomegalia/enzimologia , Hepatomegalia/genética , Heterozigoto , Humanos , Hipertensão Portal/enzimologia , Hipertensão Portal/genética , Imuno-Histoquímica , Lactente , Cirrose Hepática/enzimologia , Cirrose Hepática/genética , México , Linhagem , Fenótipo , Irmãos/etnologia , Fatores de Tempo , Ultrassonografia Doppler em Cores , Doença de Wolman/complicações , Doença de Wolman/diagnóstico , Doença de Wolman/enzimologia , Doença de Wolman/etnologia , Doença de WolmanRESUMO
Cholesterol ester storage disease (CESD) is infrequent in children. Four new cases in two nonrelated families are presented. Acid lipase deficiency in the leukocytes of the patients and reduced activity (50%) in those of parents were demonstrated. Clinical manifestations varied from neonatal cholestasis to asymptomatic hepatomegaly. Hepatic histology showed lipid vacuoles and cholesterol ester storage in hepatocytes and Kupffer cells. Increased levels of cholesterol and hepatomegaly were the first findings. There is as yet no specific treatment for CESD; however, the early detection of cases would make possible the timely control of complications.
Assuntos
Ésteres do Colesterol/metabolismo , Erros Inatos do Metabolismo Lipídico , Criança , Feminino , Hepatomegalia/enzimologia , Homozigoto , Humanos , Hipercolesterolemia/metabolismo , Células de Kupffer/enzimologia , Leucócitos/enzimologia , Erros Inatos do Metabolismo Lipídico/genética , Erros Inatos do Metabolismo Lipídico/metabolismo , Erros Inatos do Metabolismo Lipídico/patologia , Lipase Lipoproteica/deficiência , Fígado/enzimologia , Fígado/patologia , MasculinoAssuntos
Aminoácidos/metabolismo , Fígado/enzimologia , Liases/metabolismo , Distúrbios Nutricionais/enzimologia , Adaptação Fisiológica , Peso Corporal , Dietoterapia , Edema/enzimologia , Feminino , Hepatomegalia/enzimologia , Humanos , Lactente , Jamaica , Masculino , Deficiência de Proteína/enzimologiaRESUMO
Aminoacid-activating enzymes and argininosuccinase were measured in liver-biopsy samples from twenty-two malnourished and recovering Jamaican infants. Aminoacid-activating-enzyme levels were increased initially and fell on recovery; argininosuccinase activity was low initially and rose on recovery. It is suggested that these changes are part of the adaptation which takes place in aminoacid metabolism in the malnourished state. (AU)