RESUMEN

BACKGROUND: Allergic contact dermatitis (ACD) is a common human dermatosis in which not all the mechanisms involved in its pathogenesis have been elucidated. OBJECTIVE: To study the expression of CS-1 fibronectin, TARC and Th1-associated chemokine receptors in biopsies from allergic patch test reactions. MATERIAL AND METHODS: Thirteen patients already diagnosed with ACD were challenged on the back with the antigen responsible of the disease and macroscopic responses and biopsies taken after 48 h. Skin biopsies from negative control challenge sites, AD and ICD were also taken. Samples were fixed, embedded in paraffin wax and processed in order to perform histological and immunohistochemical studies. RESULTS: All subjects with ACD showed a positive clinical response and a perivascular mononuclear cell infiltration at 48 h, which was not seen in the negative controls. The majority of skin-infiltrating cells were CD4+ and CD8+ and up to 54% or 40% of them expressed CXCR3 or CCR5, respectively. We also showed expression of CS-1 fibronectin in inflamed endothelial cells not only in ACD but also in AC and ICD. In contrast TARC was only expressed in ACD and AC. CONCLUSION: We showed for the first time that CS-1 fibronectin is expressed in dermal vessels from allergic patch tests positive reactions, as well as irritant and atopic skin lesions.

Asunto(s)

Dermatitis Alérgica por Contacto/metabolismo , Endotelio Vascular/metabolismo , Péptidos/metabolismo , Adolescente , Adulto , Anciano , Antígenos CD/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico , Quimiocina CCL17 , Quimiocinas CC/metabolismo , Proteínas de Unión al ADN/metabolismo , Dermatitis Alérgica por Contacto/patología , Endotelio Vascular/patología , Femenino , Humanos , Técnicas para Inmunoenzimas , Péptidos y Proteínas de Señalización Intercelular , Masculino , Persona de Mediana Edad , Receptores CCR5/metabolismo , Receptores CXCR3 , Receptores de Quimiocina/metabolismo , Factores de Transcripción/metabolismo

RESUMEN

An Argentine male child died at 4.5 years of age of a lethal mitochondrial disease associated with a MELAS mutation and a Barth syndrome-like presentation. The child had severe failure to thrive from the early months and for approximately two years thereafter. In addition, the patient had severely delayed gross motor milestones, marked muscle weakness, and dilated cardiomyopathy that progressed to congestive heart failure. He also had persistently elevated urinary levels of 3-methylglutaconic and 2-ethylhydracrylic acids and low blood levels of cholesterol. Detailed histopathologic evaluation of the skeletal muscle biopsy showed high activity of succinate dehydrogenase, a generalized decrease of COX activity, and abundant ragged-red fibers. Electron microscopic studies revealed multiple mitochondrial abnormalities in lymphocytes and monocytes, in the striated muscle, and in the postmortem samples (muscle, heart, liver, and brain). Biochemical analysis showed a pronounced and constant lactic acidosis, and abnormal urinary organic acid excretion (unchanged in the fasting and postprandial states). In addition, in CSF there was a marked increase of lactate and beta-hydroxybutyrate (beta-HOB) and also a high systemic ratio beta-HOB/acetoacetate. Enzymatic assay of the respiratory chain in biopsied muscle showed 10% of complex I activity and 24% of complex IV activity compared with controls. Molecular studies of the mitochondrial genome revealed an A to G mutation at nucleotide pair 3243 in mitochondrial DNA, a well-known pathogenetic mutation (MELAS mutation) in all the patient's tissues and also in the blood specimens of the probands mother and sibs (4 of 5). The diagnosis of MELAS mutation was reinforced by the absence of an identifiable mutation in the X-linked G4.5 gene of the propositus. The present observation gives additional evidence of the variable clinical expression of mtDNA mutations in humans and demonstrates that all clinical variants deserve adequate investigation to establish a primary defect. It also suggests adding Barth-like syndrome to the list of phenotypes with the MELAS mutation.

Asunto(s)

ADN Mitocondrial/genética , Síndrome MELAS/genética , Mutación Puntual , Ácido 3-Hidroxibutírico/sangre , Ácidos/líquido cefalorraquídeo , Ácidos/orina , Argentina , Biopsia , Preescolar , Transporte de Electrón , Humanos , Lactatos/sangre , Lactatos/líquido cefalorraquídeo , Síndrome MELAS/diagnóstico , Masculino , Mitocondrias/enzimología , Músculo Esquelético/patología , Músculo Esquelético/ultraestructura , Fenotipo , Síndrome

RESUMEN

UNLABELLED: These ovarian neoplasm derive from the ovarian stromal component constituting around the 5 to 12% of all ovarian tumors. OBJECTIVE: To examine the histopathological and ultrastructural morphologic characteristic of the neoplastic cells and the patognomonic element of these tumors: Call Exner's Bodies MATERIALS AND METHODS: The materials corresponded to 2 women of 52 and 55 years. The syntomatology was abdominal tumor that went in increase. The materials were fractioned for the histopathological conventional study and for ultrastructural analysis. For this last one, they were fixed in Karnovsky, refix in osmio and included in Araldita. RESULTS: By means of the different observations it was determined in both cases the nuclear atipia, indentations nuclei and prominent nucleoli. In one of the cases the presence of Bodies of Call-Exner was detected, and ultrastructurally was compound by whirled fibrils and amorphous material, with dense structures electron to its around. It was interest the infiltrated of plasmatic cells around the tumors cells. These neoplasms are of interest due to their impredictible behavior and to the hormonal production that can originate alterations in other organs of the genital apparatus.

Asunto(s)

Tumor de Células de la Granulosa/patología , Tumor de Células de la Granulosa/ultraestructura , Neoplasias Ováricas/patología , Neoplasias Ováricas/ultraestructura , Femenino , Humanos , Persona de Mediana Edad

RESUMEN

These ovarian neoplasm derive from the ovarian stromal component constituting around the 5 to 12

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of all ovarian tumors. OBJECTIVE: To examine the histopathological and ultrastructural morphologic characteristic of the neoplastic cells and the patognomonic element of these tumors: Call Exners Bodies MATERIALS AND METHODS: The materials corresponded to 2 women of 52 and 55 years. The syntomatology was abdominal tumor that went in increase. The materials were fractioned for the histopathological conventional study and for ultrastructural analysis. For this last one, they were fixed in Karnovsky, refix in osmio and included in Araldita. RESULTS: By means of the different observations it was determined in both cases the nuclear atipia, indentations nuclei and prominent nucleoli. In one of the cases the presence of Bodies of Call-Exner was detected, and ultrastructurally was compound by whirled fibrils and amorphous material, with dense structures electron to its around. It was interest the infiltrated of plasmatic cells around the tumors cells. These neoplasms are of interest due to their impredictible behavior and to the hormonal production that can originate alterations in other organs of the genital apparatus.

RESUMEN

We describe a 36-year-old woman with Primary Sjögren's Syndrome (PSS). Purpura, corneal perforation, metabolic acidosis, decreased glomerular filtration, hypokalemia, hyposthenuria, and polyuria were present. Chronic renal insufficiency and renal tubular acidosis type I were diagnosed. Kidney biopsy revealed mesangial glomerulonephritis, interstitial nephritis, and tubular atrophy. Replacement treatment with saliva, tears, and potassium citrate was started. She was given prednisone and cyclophosphamide. This would be the first description of PSS, mesangial glomerulonephritis, and chronic renal insufficiency.

Asunto(s)

Fallo Renal Crónico/complicaciones , Nefritis Intersticial/complicaciones , Síndrome de Sjögren/complicaciones , Acidosis Tubular Renal/complicaciones , Acidosis Tubular Renal/patología , Adulto , Femenino , Mesangio Glomerular/patología , Humanos , Fallo Renal Crónico/patología , Nefritis Intersticial/patología , Síndrome de Sjögren/patología

RESUMEN

The results of the present study reveal an early increase in activity levels of creatine kinase and lactate dehydrogenase in the plasma of mice infected with Trypanosoma cruzi strains K-1, X-1, and Tulahuen as compared with uninfected control mice. An increase in creatine kinase activity was detected earlier in K-1- and X-1-infected mice than in Tulahuen-infected mice. Moreover, an increase in lactate dehydrogenase activity occurred at 1.5 days after infection with the X-1 and Tulahuen strains and at 3.5 days after infection with the K-1 strain. Generally, the highest activity levels were found in the plasma of mice infected with the most virulent and lethal Tulahuen strain as compared with the less virulent and nonlethal K-1 and X-1 strains. A significant decrease in creatine kinase levels occurred later in the tissues than in the plasma of K-1- and X-1-infected mice but did not vary significantly in any of the tissues from Tulahuen-infected mice. Similarly, the specific activity of lactate dehydrogenase in tissues from K-1- and X-1-infected mice dropped at a later stage than did the activity in plasma, but infection with the Tulahuen strain caused an earlier reduction in the activity of lactate dehydrogenase in the heart and skeletal muscle. The activity levels of both enzymes in plasma and tissues showed a linearly negative and statistically significant correlation. The present study reveals that levels of creatine kinase and lactate dehydrogenase activity in plasma could be early indicators of and suitable tools for monitoring of the infectivity of these strains of T. cruzi and might reflect their inherent histotropism during experimentally acute Chagas' disease.

Asunto(s)

Enfermedad de Chagas/enzimología , Creatina Quinasa/sangre , L-Lactato Deshidrogenasa/sangre , Trypanosoma cruzi/patogenicidad , Animales , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/patología , Modelos Animales de Enfermedad , Femenino , Corazón/parasitología , Hígado/enzimología , Hígado/parasitología , Hígado/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Músculo Esquelético/enzimología , Músculo Esquelético/parasitología , Músculo Esquelético/patología , Miocardio/enzimología , Miocardio/patología , Parasitemia/enzimología , Parasitemia/parasitología , Parasitemia/patología , Especificidad de la Especie

RESUMEN

We applied both hormonal and antiestrogen treatment in female Wistar rats to analyze the estrogen dependence of the growth of sarcomas induced with 9,10-dimethyl-1,2-benzanthracene. Animals bearing tumors of 10 mm in diameter were divided at random into five groups and submitted to different treatments during 24 weeks. The treatment with ovariectomy and tamoxifen in tumor-bearing animals resulted in tumor growth suppression and prolonged survival by a protection against the lethal tumor. On the other hand, the estrogen treatment exerted an adverse effect showing a faster growth of the tumors and a great decrease in survival. In summary, the antiestrogen treatment can have an antitumor effect in mesenchymal tumors, possibly by modifying the immunological status of the host.

Asunto(s)

Estrógenos/uso terapéutico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Sarcoma Experimental/tratamiento farmacológico , Tamoxifeno/uso terapéutico , Animales , Biomarcadores de Tumor/metabolismo , Femenino , Inmunohistoquímica , Neoplasias Mamarias Experimentales/metabolismo , Neoplasias Mamarias Experimentales/mortalidad , Neoplasias Mamarias Experimentales/patología , Microscopía Electrónica , Ovariectomía , Ratas , Ratas Wistar , Sarcoma Experimental/metabolismo , Sarcoma Experimental/mortalidad , Sarcoma Experimental/patología , Tasa de Supervivencia , Factores de Tiempo

RESUMEN

The use of Lectins to identify oligosaccharides in mucin substances has been increased by the role played by cell surface carbohydrates in invasion and metastasis processes. We studied in this work normal endometrial tissue, with benign and malignant entities in search for the presence of the Galactose beta 1-3 N Acetylgalactosamine(Gal beta 1-3 GalNAC alpha and Galactose beta 1-3 N Acetylgalactosamine (Gal beta 1-3 alpha and beta) using the Lectins: Agaricus bisporus (ABL) and Arachis hipogea (PNA) respectively. The specific control were baths with galactose for PNA and with porcine stomach mucin for ABL. The use of these two Lectins allowed to differentiate substances bonded or non bonded to Sialic Acid, since PNA fails to label when the oligosaccharide is bonded to this acid Sialic. Significant differences were noticed on the bonding patterns of both Lectins on tissues with benign, malignant and normal entities. In this latter case the labelling was always continuous in both Lectins whereas it was irregular in the carcinoma.

Asunto(s)

Endometrio/química , Galactosa/aislamiento & purificación , Lectinas/fisiología , Mucinas/química , Biomarcadores , Carcinoma/metabolismo , Hiperplasia Endometrial/metabolismo , Neoplasias Endometriales/metabolismo , Femenino , Humanos

RESUMEN

The use of Lectins to identify oligosaccharides in mucin substances has been increased by the role played by cell surface carbohydrates in invasion and metastasis processes. We studied in this work normal endometrial tissue, with benign and malignant entities in search for the presence of the Galactose beta 1-3 N Acetylgalactosamine(Gal beta 1-3 GalNAC alpha and Galactose beta 1-3 N Acetylgalactosamine (Gal beta 1-3 alpha and beta) using the Lectins: Agaricus bisporus (ABL) and Arachis hipogea (PNA) respectively. The specific control were baths with galactose for PNA and with porcine stomach mucin for ABL. The use of these two Lectins allowed to differentiate substances bonded or non bonded to Sialic Acid, since PNA fails to label when the oligosaccharide is bonded to this acid Sialic. Significant differences were noticed on the bonding patterns of both Lectins on tissues with benign, malignant and normal entities. In this latter case the labelling was always continuous in both Lectins whereas it was irregular in the carcinoma.

RESUMEN

Impaired immune responses occur frequently in cancer patients or in tumor-bearing animals, but the mechanisms of the tumor-induced immune defects remain poorly understood. The aim of the present study was to determine the relevance of the immune system in the control of tumor growth. We have developed a model of progressive and non-progressive mammary tumor, chemically induced in female Wistar rats. In this model we evaluated the development of an immune response after immunization of rats bearing progressive and non-progressive tumors with a non-related antigen, such as sheep red blood cells. We also studied the activation state of peritoneal macrophages from animals bearing tumors by evaluating the production of free radicals. Our findings indicated that the cell-mediated immunity in rats bearing progressive tumors fails to respond to heterologous antigen in vivo, as demonstrated by a negative delayed-type hypersensitivity reaction, and is accompanied by minor nitric oxide production by peritoneal exudate cells as well as a lower capacity for macrophage activation. The study of non-progressive tumor-bearing rats indicated that the cell-mediated immune response was intact and an activated state of macrophages was found in vivo. The results described in this paper should be taken into account when therapies based on cancer vaccines are chosen for the treatment of cancer.

Asunto(s)

Adenocarcinoma/inmunología , Neoplasias Mamarias Experimentales/inmunología , 9,10-Dimetil-1,2-benzantraceno , Adenocarcinoma/inducido químicamente , Adenocarcinoma/patología , Animales , Carcinoma Ductal de Mama/inducido químicamente , Carcinoma Ductal de Mama/inmunología , Carcinoma Ductal de Mama/patología , Progresión de la Enfermedad , Eritrocitos/inmunología , Femenino , Pruebas de Hemaglutinación , Hipersensibilidad Tardía/inmunología , Inmunidad Celular , Inmunización , Activación de Macrófagos , Macrófagos Peritoneales/inmunología , Neoplasias Mamarias Experimentales/inducido químicamente , Neoplasias Mamarias Experimentales/patología , Óxido Nítrico/biosíntesis , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Ovinos/sangre

Asunto(s)

Factor Natriurético Atrial/metabolismo , Enfermedad de Chagas/metabolismo , Enfermedad Aguda , Animales , Factor Natriurético Atrial/sangre , Enfermedad de Chagas/sangre , Enfermedad de Chagas/patología , Atrios Cardíacos/metabolismo , Atrios Cardíacos/patología , Inmunohistoquímica , Ratas , Ratas Wistar , Factores de Tiempo

RESUMEN

We report on a 20-year-old male with a beta-glucuronidase (GUSB) deficiency mucopolysaccharidosis. He had pectus carinatum, gross thoracic kyphoscoliosis, and hip dysplasia, a picture which became conspicuous after age 4 years. Hepatosplenomegaly, herniae, corneal clouding, and neurological abnormalities were absent. Although he had Alder-type granulations in his polymorphonuclear leukocytes, the urine did not contain a significant excess of mucopolysaccharides. Electron microscopic examination of skin and gingival biopsies, leukocytes, and cultured skin fibroblasts showed numerous single membrane-limited vacuoles either empty or filled with fibrillogranular material; this last tissue did not contain metachromatic granules. Radiographs demonstrated a distinct spondyloepiphyseal dysplasia in which the most striking changes were confined to the thoracic spine (flattening and collapse in T7, T8 and T10 vertebral bodies) and to the femoral capital epiphyses (irregularities and fragmentation). The activity of GUSB in the patient's serum, leukocytes, and fibroblasts was severely decreased; the GUSB activity in the serum and leukocytes from the parents and 2 asymptomatic sibs was subnormal. Immunoblot analysis showed very low levels of cross-reactive material towards anti-GUSB antiserum in the patient's leukocyte and fibroblast extracts. This patient was more severely affected in his skeleton than other described patients with an oligosymptomatic chronic form. This case broadens the clinical and biochemical picture associated with GUSB deficiency and may represent a new variant of the disease.

Asunto(s)

Mucopolisacaridosis VII/patología , Osteocondrodisplasias/genética , Adulto , Enfermedad Crónica , Glucuronidasa/deficiencia , Articulación de la Cadera/diagnóstico por imagen , Humanos , Leucocitos/enzimología , Leucocitos/ultraestructura , Masculino , Microscopía Electrónica , Mucopolisacaridosis VII/enzimología , Mucopolisacaridosis VII/genética , Osteocondrodisplasias/enzimología , Osteocondrodisplasias/patología , Huesos Pélvicos/diagnóstico por imagen , Radiografía , Piel/enzimología , Piel/ultraestructura , Columna Vertebral/diagnóstico por imagen

Asunto(s)

Factor Natriurético Atrial/metabolismo , Enfermedad de Chagas/metabolismo , Enfermedad Aguda , Animales , Ratas , Ratas Wistar , Factores de Tiempo

RESUMEN

In this paper we discuss the first five Argentinean patients presenting isovaleric acidemia (IVA), an alteration of leucine catabolism due to a genetic defect of isovaleryl-CoA dehydrogenase. Belonging to unrelated families, one from native (H. Fam.) and the other from Italian ancestry (M. Fam.); the patients presented the clinical pattern highly suggestive of the disease: they were siblings, had disease-free intervals, vomiting, ketoacidosis crises, "sweaty feet" odor and progression of the neurologic involvement from somnolence and stupor to profound coma. In the four children of H. Fam. the disease had a late but severe beginning; one of the girls died (N.H.). The boy from M. Fam. presented a neonatal form of clearly benign course. The disease was confirmed by gas-chromatography (GC) of volatile acids in serum and also by the typical urinary acid GC-profiles (Fig. 1, A and B); the isovalerylglycine quantitative evaluation in urinary samples collected during crises is shown in Table 1. The morphological findings in liver and brain of N.H. showed at the ultrastructural study, an extensive fatty degeneration and greatly marked mitochondrial alterations in the liver and edema, neuronal karyorrhexis and karyolysis in the brain (Fig. 2). The therapeutic protocol based on a low leucine or low protein diet and use of glycine is described. The evolutionary follow up, more than 10 years for the first case, showed a normal mental development in three of them and retardation in the first child of H. Fam., who had a late diagnosis. IVA is still valuable as a paradigm in the acquisition of a highly clinical suspicion and for its introduction in the study of genetic organic acidemias.

Asunto(s)

Acidosis/genética , Glicina/análogos & derivados , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Oxidorreductasas/deficiencia , Ácidos Pentanoicos/sangre , Encéfalo/ultraestructura , Preescolar , Cromatografía en Capa Delgada , Familia , Femenino , Estudios de Seguimiento , Hemiterpenos , Humanos , Lactante , Isovaleril-CoA Deshidrogenasa , Hígado/ultraestructura , Masculino , Fenotipo

RESUMEN

La acidemia isovalérica (AIV) es una enfermedad genética causada por una deficiencia de la isovaleril-CoA dehidrogenasa, enzima involucrada en un paso catabólico de la leucina. El cuadro clínico se caracteriza por crisis cetoacidóticas, progresivo compromiso neurológico y olor a "sudor de pies". En este trabajo se presentan los primeros cinco pacientes argentinos pertenecientes a dos familias no emparentadas. En una de ellas, los cuatro hijos afectados manifestaron una severa forma crónica intermitente con muerte de uno de los enfermos (N.H.). En el niño de la segunda familia, la AIV se expresó como una forma neonatal de curso inusualmente benigno. El diagnóstico definitivo se realizó con el análisis de los ácidos orgánicos por cromatografía gaseosa la cual confirmó el masivo incremento sérico del ácido isovalérico durante las crisis y la presencia permanente de la isovaleriglicina en las orinas de crisis y en las de remisión. La ultraestructura del hígado y cerebro de H.H. señlaron para el primero metamorfosis grasa y marcados cambios en las mitocondrias; en el cerebro, las células neuronales y gliales evidencian acentuada tumefacción, alteraciones en sus organoides, cariorrexis. El largo seguimiento clínico, alrededor de diez años para el primer paciente, permitió observar por un lado, una disminución, alteraciones en sus organoides, cariolisis y cariorrexis. El largo seguimiento clínico, alrededor de diez años para el primer paciente, permitió observar por un lado, una disminución gradual de la frecuencia y severidad de las crisis con el desarrollo y tendencia a desaparecer entre los 6 y 7 años de edad; por otra parte fue posible calificar como efecto diferenciado sobre la vida e intelecto de los enfermos, la precocidad del tratamiento de la emergencia metabólica y del dietético pero también dependiente del fenotipo que la heterogeneidad marcó para cada uno de ellos. La experiencia genéticas y para adquirir una alta sospecha clínica frente a estas inéditas patologías en nuestro medio (AU)

Asunto(s)

Humanos , Masculino , Femenino , Lactante , Preescolar , Acidosis/genética , Glicina/análisis , Oxidorreductasas/sangre , Cromatografía en Capa Delgada , Hígado/ultraestructura , Cerebro/ultraestructura , Fenotipo , Estudios de Seguimiento

RESUMEN

La acidemia isovalérica (AIV) es una enfermedad genética causada por una deficiencia de la isovaleril-CoA dehidrogenasa, enzima involucrada en un paso catabólico de la leucina. El cuadro clínico se caracteriza por crisis cetoacidóticas, progresivo compromiso neurológico y olor a "sudor de pies". En este trabajo se presentan los primeros cinco pacientes argentinos pertenecientes a dos familias no emparentadas. En una de ellas, los cuatro hijos afectados manifestaron una severa forma crónica intermitente con muerte de uno de los enfermos (N.H.). En el niño de la segunda familia, la AIV se expresó como una forma neonatal de curso inusualmente benigno. El diagnóstico definitivo se realizó con el análisis de los ácidos orgánicos por cromatografía gaseosa la cual confirmó el masivo incremento sérico del ácido isovalérico durante las crisis y la presencia permanente de la isovaleriglicina en las orinas de crisis y en las de remisión. La ultraestructura del hígado y cerebro de H.H. señlaron para el primero metamorfosis grasa y marcados cambios en las mitocondrias; en el cerebro, las células neuronales y gliales evidencian acentuada tumefacción, alteraciones en sus organoides, cariorrexis. El largo seguimiento clínico, alrededor de diez años para el primer paciente, permitió observar por un lado, una disminución, alteraciones en sus organoides, cariolisis y cariorrexis. El largo seguimiento clínico, alrededor de diez años para el primer paciente, permitió observar por un lado, una disminución gradual de la frecuencia y severidad de las crisis con el desarrollo y tendencia a desaparecer entre los 6 y 7 años de edad; por otra parte fue posible calificar como efecto diferenciado sobre la vida e intelecto de los enfermos, la precocidad del tratamiento de la emergencia metabólica y del dietético pero también dependiente del fenotipo que la heterogeneidad marcó para cada uno de ellos. La experiencia genéticas y para adquirir una alta sospecha clínica frente a estas inéditas patologías en nuestro medio

Asunto(s)

Humanos , Masculino , Femenino , Lactante , Preescolar , Acidosis/genética , Glicina/análisis , Oxidorreductasas/sangre , Cerebro/ultraestructura , Cromatografía en Capa Delgada , Hígado/ultraestructura , Estudios de Seguimiento , Fenotipo

RESUMEN

In this paper we discuss the first five Argentinean patients presenting isovaleric acidemia (IVA), an alteration of leucine catabolism due to a genetic defect of isovaleryl-CoA dehydrogenase. Belonging to unrelated families, one from native (H. Fam.) and the other from Italian ancestry (M. Fam.); the patients presented the clinical pattern highly suggestive of the disease: they were siblings, had disease-free intervals, vomiting, ketoacidosis crises, [quot ]sweaty feet[quot ] odor and progression of the neurologic involvement from somnolence and stupor to profound coma. In the four children of H. Fam. the disease had a late but severe beginning; one of the girls died (N.H.). The boy from M. Fam. presented a neonatal form of clearly benign course. The disease was confirmed by gas-chromatography (GC) of volatile acids in serum and also by the typical urinary acid GC-profiles (Fig. 1, A and B); the isovalerylglycine quantitative evaluation in urinary samples collected during crises is shown in Table 1. The morphological findings in liver and brain of N.H. showed at the ultrastructural study, an extensive fatty degeneration and greatly marked mitochondrial alterations in the liver and edema, neuronal karyorrhexis and karyolysis in the brain (Fig. 2). The therapeutic protocol based on a low leucine or low protein diet and use of glycine is described. The evolutionary follow up, more than 10 years for the first case, showed a normal mental development in three of them and retardation in the first child of H. Fam., who had a late diagnosis. IVA is still valuable as a paradigm in the acquisition of a highly clinical suspicion and for its introduction in the study of genetic organic acidemias.

RESUMEN

In this paper we discuss the first five Argentinean patients presenting isovaleric acidemia (IVA), an alteration of leucine catabolism due to a genetic defect of isovaleryl-CoA dehydrogenase. Belonging to unrelated families, one from native (H. Fam.) and the other from Italian ancestry (M. Fam.); the patients presented the clinical pattern highly suggestive of the disease: they were siblings, had disease-free intervals, vomiting, ketoacidosis crises, [quot ]sweaty feet[quot ] odor and progression of the neurologic involvement from somnolence and stupor to profound coma. In the four children of H. Fam. the disease had a late but severe beginning; one of the girls died (N.H.). The boy from M. Fam. presented a neonatal form of clearly benign course. The disease was confirmed by gas-chromatography (GC) of volatile acids in serum and also by the typical urinary acid GC-profiles (Fig. 1, A and B); the isovalerylglycine quantitative evaluation in urinary samples collected during crises is shown in Table 1. The morphological findings in liver and brain of N.H. showed at the ultrastructural study, an extensive fatty degeneration and greatly marked mitochondrial alterations in the liver and edema, neuronal karyorrhexis and karyolysis in the brain (Fig. 2). The therapeutic protocol based on a low leucine or low protein diet and use of glycine is described. The evolutionary follow up, more than 10 years for the first case, showed a normal mental development in three of them and retardation in the first child of H. Fam., who had a late diagnosis. IVA is still valuable as a paradigm in the acquisition of a highly clinical suspicion and for its introduction in the study of genetic organic acidemias.

RESUMEN

En los 26 años transcurridos desde la descripción original de la deficiencia en glucógeno sintetasa hepática, sólo una observación casuística más fue referida en 1977. Nosotros presentamos los estudios efectuados en un niño argentino de ascendencia italiana quién manifestó a partir de los 21 meses de edad, signos de disfunción hepática con escasa sintomatología clínica que contrastaba con una muy marcada metamorfosis grasa de su hígado. Una respuesta totalmente atípica a la sobrecarga con fructosa fue la clave inicial de orientación diagnóstica. El glucagon no modificó significativamente los niveles de glucosa después de un ayuno de 12 horas pero sí elevó la glucemia, con caída del lactato y alanina a las 3 horas de una comida. Un perfil metabólico de 24 horas demostró hipoglucemia, hipercetonemia, bajas concentraciones de alanina y moderada lactoacidemia en ayunas e hiperglucemia y marcado aumento del lactato en condiciones postprandiales; este perfil reducido a 14 horas, 12 horas de ayuno y a 2 horas posteriores a una ingesta, reveló iguales alteraciones en un hermano menmor asintomático. El curso de la investigación condujo a una segunda biopsia hepática que confirmó la esteatosis hepática y al examen ultraestructural alteracioens subcelulares en hígado y tambien en músculo; además se comprobó el bajo contenido del flucogéno hepático y una actividad de la glucógeno sintetasa entre el 20,25% de los controles siendo por el contrario normal la actividad de la enzima en músculo y en fibroblastos cultivados de una biopsia de piel. La falta de expresión clínica de la hipoglucemia, incluyendo convulsiones y/o retardo mental y un desarrollo pondoestatural normal, señalan a esta casuística argentina como una variante menos severa de la enfermedad respecto a las descripciones previas, observación que podría estar en correlación al defecto parcial en la actividad de la glucógeno sintetasa hepática (AU)

Asunto(s)

Humanos , Preescolar , Masculino , Enfermedad del Almacenamiento de Glucógeno/genética , Glucógeno Sintasa/deficiencia , Enfermedad del Almacenamiento de Glucógeno/sangre , Enfermedad del Almacenamiento de Glucógeno/patología , Fenotipo , Hígado/enzimología , Hígado/patología , Biopsia , Fructosa/diagnóstico , Glucagón/diagnóstico

RESUMEN

En los 26 años transcurridos desde la descripción original de la deficiencia en glucógeno sintetasa hepática, sólo una observación casuística más fue referida en 1977. Nosotros presentamos los estudios efectuados en un niño argentino de ascendencia italiana quién manifestó a partir de los 21 meses de edad, signos de disfunción hepática con escasa sintomatología clínica que contrastaba con una muy marcada metamorfosis grasa de su hígado. Una respuesta totalmente atípica a la sobrecarga con fructosa fue la clave inicial de orientación diagnóstica. El glucagon no modificó significativamente los niveles de glucosa después de un ayuno de 12 horas pero sí elevó la glucemia, con caída del lactato y alanina a las 3 horas de una comida. Un perfil metabólico de 24 horas demostró hipoglucemia, hipercetonemia, bajas concentraciones de alanina y moderada lactoacidemia en ayunas e hiperglucemia y marcado aumento del lactato en condiciones postprandiales; este perfil reducido a 14 horas, 12 horas de ayuno y a 2 horas posteriores a una ingesta, reveló iguales alteraciones en un hermano menmor asintomático. El curso de la investigación condujo a una segunda biopsia hepática que confirmó la esteatosis hepática y al examen ultraestructural alteracioens subcelulares en hígado y tambien en músculo; además se comprobó el bajo contenido del flucogéno hepático y una actividad de la glucógeno sintetasa entre el 20,25% de los controles siendo por el contrario normal la actividad de la enzima en músculo y en fibroblastos cultivados de una biopsia de piel. La falta de expresión clínica de la hipoglucemia, incluyendo convulsiones y/o retardo mental y un desarrollo pondoestatural normal, señalan a esta casuística argentina como una variante menos severa de la enfermedad respecto a las descripciones previas, observación que podría estar en correlación al defecto parcial en la actividad de la glucógeno sintetasa hepática

Asunto(s)

Humanos , Preescolar , Masculino , Enfermedad del Almacenamiento de Glucógeno/genética , Glucógeno Sintasa/deficiencia , Biopsia , Enfermedad del Almacenamiento de Glucógeno/sangre , Enfermedad del Almacenamiento de Glucógeno/patología , Fructosa , Glucagón , Hígado/enzimología , Hígado/patología , Fenotipo