[Molecular and clinical characterization of Colombian patients suffering from type III glycogen storage disease].

INTRODUCTION: Type III glycogen storage disease (GSD III) is an autosomal recessive disorder in which a mutation in the AGL gene causes deficiency of the glycogen debranching enzyme. The disease is characterized by fasting hypoglycemia, hepatomegaly and progressive myopathy. Molecular analyses of AGL have indicated heterogeneity depending on ethnic groups. The full spectrum of AGL mutations in Colombia remains unclear. OBJECTIVE: To describe the clinical and molecular characteristics of ten Colombian patients diagnosed with GSD III. MATERIALS AND METHODS: We recruited ten Colombian children with a clinical and biochemical diagnosis of GSD III to undergo genetic testing. The full coding exons and the relevant exon-intron boundaries of the AGL underwent Sanger sequencing to identify mutation. RESULTS: All patients had the classic phenotype of the GSD III. Genetic analysis revealed a mutation p.Arg910X in two patients. One patient had the mutation p.Glu1072AspfsX36, and one case showed a compound heterozygosity with p.Arg910X and p.Glu1072AspfsX36 mutations. We also detected the deletion of AGL gene 3, 4, 5, and 6 exons in three patients. The in silico studies predicted that these defects are pathogenic. No mutations were detected in the amplified regions in three patients. CONCLUSION: We found mutations and deletions that explain the clinical phenotype of GSD III patients. This is the first report with a description of the clinical phenotype and the spectrum of AGL mutations in Colombian patients. This is important to provide appropriate prognosis and genetic counseling to the patient and their relatives.

Hepatitis E Virus Genotype 3 in Colombia: Survey in Patients with Clinical Diagnosis of Viral Hepatitis.

BACKGROUND: Hepatitis E virus is a major cause of outbreaks as well as sporadic hepatitis cases worldwide. The epidemiology of this enterically transmitted infection differs between developing and developed countries. The aims of this study were to describe HEV infection in Colombian patients and to characterize the genotype. METHODS: A prospective study was carried out on 40 patients aged over 15 with a clinical diagnosis of viral hepatitis, recruited from five primary health units in the city of Medellin, Colombia. Fecal samples obtained from the 40 consecutives cases were analyzed for HEV RNA using nested reverse transcription PCR for both ORF1 and ORF2-3. The amplicons were sequenced for phylogenetic analyses. RESULTS: Nine (22.5%) cases of HEV infection were identified in the study population. Three HEV strains obtained from patients were classified as genotype 3. No significant association was found between cases of Hepatitis E and the variables water drinking source, garbage collection system and contact with pigs. CONCLUSIONS: This is the first prospective study of hepatitis E in Colombian patients. The circulation of the genotype 3 in this population is predictable considering the reports of the region and the identification of this genotype from pigs in the state of Antioquia, of which Medellin is the capital. Further studies are necessary to establish whether zoonotic transmission of HEV is important in Colombia.

Extrahepatic portal vein aneurysm after liver transplantation in a child: case report.

Portal vein aneurysms are very rare and represent <3% of all venous aneurysms. They can be congenital or acquired. Most patients do not have liver disease at diagnosis. Although uncommon, portal vein aneurysm has been described after liver transplant. We report the case of a six-yr-old girl who presented with an aneurysm of the extrahepatic portal vein after segmental liver transplantation. Because the patient was asymptomatic and owing to its extrahepatic location, this aneurysm has been successfully followed by clinical exam and imaging for four yr.

Síndrome de Alagille experiencia clínica de catorce casos en Medellín, Colombia / Alagille syndrome, clinical experience of fourteen cases in Medellin, Colombia

Introducción: El Síndrome de Alagille corresponde a una alteración autosómica dominante con expresión variable. Se caracteriza por colestasis crónica con escasez de los conductos biliares interlobulares asociada a alteraciones cardiovasculares, oftálmicas, sistema esquelético, riñones y facies característica. Su distribución es mundial con frecuencia de 1 por cada 100000 nacidos vivos. Objetivo: Describir las características clínicas, la evolución y la sobrevida de catorce pacientes, con diagnóstico de Síndrome de Alagille atendidos en un período de 16 años en Medellín, Colombia. Materiales y métodos: Es un trabajo observacional descriptivo de reporte de casos de los hallazgos morfológicos y la evolución de los pacientes con diagnóstico de Síndrome de Alagille. Resultados: Grupo compuesto por ocho niños y seis niñas, con edades entre los dos meses y los diez años al momento de diagnóstico. El síndrome completo se presentó en 28%. Los hallazgos más frecuentes, estenosis valvular de la arteria pulmonar y la alteración vertebral se presentaron en el 79%. Tres pacientes 21%, fallecieron, uno de ellos después de recibir trasplante hepático. De los once sobrevivientes dos niñas fueron sometidas a trasplante y se encuentran en buenas condiciones. Los nueve restantes padecen hepatopatía colestásica crónica y reciben tratamiento médico. Conclusión: El Síndrome de Alagille se debe tener en cuenta en el diagnóstico de colestasis crónica infantil. Para establecer la distribución y frecuencia de esta enfermedad en nuestro país es necesario desarrollar investigaciones que idealmente incluyan el estudio de la mutación genética en los pacientes y su familia cercana.

Introduction: The Alagille Syndrome is an autosomic dominant disorder with variable expression. Chronic cholestasis, characteristic facial appearance and abnormalities heart, skeleton, eye, kydnes with hypoplasia of the biliary ducts. Initial description in France, with mundial distribution her frecuence is 1/100000. Objective: To describe the clinical characteristic and evolutions of fourteen patients with diagnosis Alagille Syndrome in Medellín Colombia. Materials and methods: Descriptive retrospective study with variables obtained from clinical records of patients with diagnosis Alagille Syndrome. Results: Eight boys and six girls. The age at diagnosis varied two months at nine years. Complete syndrome was present in 28%. The most frecuent alterations were valvular stenosis pulmonary artery and failure of anterior vertebral arch fusion (butterfly vertebrae) 79%. The clinical evolution was variable, death occurred in three patients 21%, one girl post liver transplantation. Nine children had chronic hepatopathy controlled with medical treatment and two girls had liver transplantation with satisfactory evolution. Conclusions: In Colombia, the poblational incidence is not defined it is necessary to know the distribution of syndrome at future study.

Modificación del Almidón de maiz y sus efectos en el tratamiento de niños con glucogenosis / Modification of starch corn and its effects on the treatment of children with glycogenosis

Introducción: El almidón de maíz (AM) está indicado en el manejo de niños con glucogenosis hepática (GH).Objetivo: Describir la respuesta clínica en siete niños con GH I y III, del Hospital Pablo Tobón Uribe de Medellín, Colombia, al cambiar el AM de uso alimenticio (UA), por AM de pureza farmacológica (PF). Metodología: Estudio observacional, retrospectivo, descriptivo realizado en 51 meses en el que se comparan pruebas bioquímicas y evolución clínica de siete niños ambulatorios con GH, quienes recibían AMUA y se les cambió a AMPF, por recaída en sus controles bioquímicos, relacionados con el cambio en la composición del AM tradicional, al que se le adicionó una mezcla de vitaminas y minerales. Resultados: Se incluyeron 3 niñas y 4 niños entre 13 y 148 meses, 3 con GH I y 4 con GH III, que recibían AMUA, y luego de cambiar a AMPF, presentaron mejoría clínica y bioquímica así: glucemia en ayunas de 77 mg/dL (48-90) a 85 (68-119) mg/dL, ALT de 390 U/L (47-1410) a 159 (47-345) U/L y triglicéridos de 487 (186-1797) mg/dL a 240 (112-614) mg/dL.Conclusiones: El AMPF en niños con GH I y III, demostró resultados mejores, que los obtenidos con el AMUA. La evidencia bioquímica y clínica, permite recomendar su utilización en el tratamiento actual de los pacientes con estos tipos de GH.

Introduction: Corn starch (CS) is indicated for the management of children with liver glucogenosis (LG). Objective: To describe the clinic outcome in 7 children with LG I and III, from Hospital Pablo Tobón Uribe from Medellín, Colombia, to change food (F) CS by the pharmacological purity (PP) CS. Methods: Observational, retrospective, descriptive study performed in 51 months comparing biochemical and clinical course of 7 children outpatient with LG, those receiving FCS and were switched to PPCS by relapse in biochemical controls related to the change in the composition of the traditional commercial CS, which was added a mixture of vitamins and minerals. Results: Were included 3 girls and 4 boys between 13 and 148 months, 3 with LG I and 4 with LG III, receiving FCS, and after switching to PPCS, they improved the biochemical tests and clinical status. Conclusions: PPCS in children with LG I and III, showed better results than those obtained with FCS. The biochemical and clinical evidence both to recommend its use in the current treatment of patients with these types of LG.

Hepatotoxicidad detectada en un hospital de cuarto nivel en la ciudad de Medellín / Hepatotoxicity detected in a fourth-level hospital at the city of Medellín

El hígado es el principal órgano que sirve de primer paso en la biotransformación de la mayoría de los medicamentos, los cuales en algunos casos pueden conllevar a toxicidad hepática, debido a la acción tóxica directa y/o factores idiosincráticos. El diagnóstico suele ser difícil y por ello se han establecido escalas para evaluar daño hepático inducido por medicamentos. El objetivo de nuestro estudio consiste en describir las características clínicas, bioquímicas y epidemiológicas de los casos de hepatotoxicidad medicamentosa documentadas en las historias clínicas de los pacientes evaluados por la unidad de hepatología de un hospital de cuarto nivel en la ciudad de Medellín, Hospital Pablo Tobón Uribe (HPTU), entre enero 2001 y enero 2008. Se presenta un análisis estadístico de 42 casos de hepatotoxicidad medicamentosa atribuida a fármacos como los antibióticos, inmunosupresores, anticonvulsivantes, analgésicos, entre otros. Todos fueron evaluados por la escala de daño hepático inducida por medicamentos y tuvieron desenlaces como hepatitis aguda, falla hepática, trasplante, etc.

The liver is the main first-step organ involved in the metabolism of most medications. Therefore it is vulnerable to drug toxicity in some cases, due to direct toxic action and/or to idiosyncratic factors. The diagnosis is usually difficult; therefore there are some scales whose purpose is to assess hepatic damage induced by drugs. The objective of our study is to describe the clinical, biochemical and epidemiological characteristics of cases of hepatotoxicity documented in the case histories of patients evaluated by the hepatology unit of a fourth-level hospital in the city of Medellin, Hospital Pablo Tobón Uribe (HPTU), between January 2001 and January 2008. A statistical analysis is presented of 42 cases of liver toxicity ascribed to drugs such as antibiotics, immunosuppressants, antiepileptics, and analgesics, among others. All were evaluated using the scale of hepatic damage induced by medications, and they had outcomes like acute hepatitis, hepatic failure, transplant, etc.