RESUMEN
BACKGROUND: Oligosaccharidoses, which belong to the lysosomal storage diseases, are inherited metabolic disorders due to the absence or the loss of function of one of the enzymes involved in the catabolic pathway of glycoproteins and indirectly of glycosphingolipids. This enzymatic deficiency typically results in the abnormal accumulation of uncompletely degraded oligosaccharides in the urine. Since the clinical features of many of these disorders are not specific for a single enzyme deficiency, unambiguous screening is critical to limit the number of costly enzyme assays which otherwise must be performed. METHODS: Here we provide evidence for the advantages of using a MALDI-TOF/TOF (matrix-assisted laser desorption ionization time-of-flight) mass spectrometric (MS) method for screening oligosaccharidoses. Urine samples from previously diagnosed patients or from unaffected subjects were randomly divided into a training set and a blind testing set. Samples were directly analyzed without prior treatment. RESULTS: The characteristic MS and MS/MS molecular profiles obtained allowed us to identify fucosidosis, aspartylglucosaminuria, GM1 gangliosidosis, Sandhoff disease, α-mannosidosis, sialidosis and mucolipidoses type II and III. CONCLUSIONS: This method, which is easily run in less than 30 minutes, is performed in a single step, and is sensitive and specific. Invaluable for clinical chemistry purposes this MALDI-TOF/TOF mass spectrometry procedure is semi-automatizable and suitable for the urinary screening of oligosacharidoses.
Asunto(s)
Enfermedades por Almacenamiento Lisosomal/metabolismo , Oligosacáridos/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Espectrometría de Masas en Tándem/métodos , Femenino , Humanos , MasculinoRESUMEN
The role of a secondary respiratory chain deficiency as an additional mechanism to intoxication, leading to development of long-term energy-dependent complications, has been recently suggested in patients with propionic acidemia (PA). We show for the first time a coenzyme Q(10) (CoQ(10)) functional defect accompanied by a multiple organ oxidative phosphorylation (OXPHOS) deficiency in a child who succumbed to acute heart failure in the absence of metabolic stress. Quinone-dependent activities in the liver (complex I+III, complex II+III) were reduced, suggesting a decrease in electron transfer related to the quinone pool. The restoration of complex II+III activity after addition of exogenous ubiquinone to the assay system suggests CoQ(10) deficiency. Nevertheless, we disposed of insufficient material to perform direct measurement of CoQ(10) content in the patient's liver. Death occurred before biochemical diagnosis of OXPHOS deficiency could be made. However, this case highlights the usefulness of rapidly identifying CoQ(10) defects secondary to PA since this OXPHOS disorder has a good treatment response which could improve heart complications or prevent their appearance. Nevertheless, further studies will be necessary to determine whether CoQ(10) treatment can be useful in PA complications linked to CoQ(10) deficiency.
Asunto(s)
Insuficiencia Cardíaca/diagnóstico , Enfermedades Mitocondriales/complicaciones , Acidemia Propiónica/complicaciones , Acidemia Propiónica/diagnóstico , Ubiquinona/análogos & derivados , Niño , Complejo I de Transporte de Electrón/deficiencia , Complejo II de Transporte de Electrones/deficiencia , Complejo III de Transporte de Electrones/deficiencia , Humanos , Hígado/enzimología , Hígado/metabolismo , Masculino , Enfermedades Mitocondriales/genética , Ubiquinona/deficiencia , Ubiquinona/genéticaRESUMEN
Mutations within the mitochondrially encoded cytochrome b (MTCYB) gene are heteroplasmic and lead to severe exercise intolerance. We describe an unusual clinical presentation secondary to a novel homoplasmic mutation within MTCYB. The m.15635T>C transition (S297P) was carried by a newborn who presented with a polyvisceral failure. This mutation was responsible for a complex III deficiency. It was homoplasmic in all tissues tested and was undetectable in patient's mother. Functional analyses, including studies on patient's cybrid cell lines, demonstrate the pathogenicity of this variant. Our data show that mutations within MTCYB can be responsible for severe phenotype at birth.
Asunto(s)
Citocromos b/deficiencia , Citocromos b/genética , ADN Mitocondrial/genética , Enfermedades Mitocondriales/genética , Insuficiencia Multiorgánica/genética , Mutación Missense , Mutación Puntual , Adulto , Niño , Humanos , Recién Nacido , Masculino , Adulto JovenRESUMEN
BACKGROUND & AIMS: Anorexia is frequent in the malnourished elderly. We studied the effects of age, nutritional status and refeeding on the expression and secretion of the orexigenic peptide ghrelin. METHODS: Four groups were prospectively enrolled: 11 undernourished elderly (80+/-6 y, BMI: 17.4+/-1.9 [Mean+/-SD]), nine well-nourished elderly (76+/-9 y, 23.5+/-2.0), 10 undernourished young (26+/-6 y, 15.1+/-1.9) and 10 well-nourished young (34+/-8 y, 22.2+/-2.7). Fasting and postprandial plasma ghrelin and other hormones (every 30 min) were measured at baseline and after a 21-day enteral nutrition in malnourished patients. Gastric ghrelin mRNA levels were measured by RT-PCR at baseline in all subjects. RESULTS: Ghrelin was significantly higher in undernourished (2151+/-871 ng/L) than in well-nourished (943+/-389 ng/L) adults, whereas there were no differences between undernourished (1544+/-758 ng/L) and well-nourished (1154+/-541 ng/L) elderly. Refeeding did not influence ghrelin levels. Gastric ghrelin mRNA levels were similar in all groups. CONCLUSIONS: There is an absence of malnutrition-induced increase of plasma ghrelin levels in elderly subjects. This feature, post-transcriptional, may be important in the lack of adaptation of elderly subjects to malnutrition.
Asunto(s)
Envejecimiento/fisiología , Alimentos , Ghrelina/sangre , Desnutrición/sangre , Adulto , Anciano , Anciano de 80 o más Años , Anorexia/sangre , Nutrición Enteral , Ayuno , Ghrelina/genética , Humanos , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estómago/químicaRESUMEN
Despite the simplicity and efficacy of TVT, this technique, like all surgical treatments, is nevertheless associated with sometimes very serious complications. The authors report a case of chronic infection of a polypropylene implant presenting with cutaneous fistula of a retropubic abscess without an associated septic syndrome, ten months after TVT insertion. The TVT was removed by mini-laparotomy after failure of three weeks of adapted antibiotics and local wound care. These infections can be explained by the capacity of certain micro-organisms to bind to biomaterials and produce a biofilm, protecting from the action of antibiotics and immune cells.