RESUMEN
Gaucher disease is an autosomal recessive disorder, characterized by decreased levels of the lysosomal enzyme glucocerebrosidase. This deficiency results in a decreased breakdown of this glycosphingolipid glucocerebroside, which accumulates in the lysosomes of the monocyte-macrophage system. It is the most common form of sphingolipidosis. Clinically, the principle signs of Gaucher's disease are hepatosplenomegaly, bone involvement, hematological changes and CNS involvement. The diagnosis of Gaucher disease has to be confirmed by the measurement of the activity of the enzyme glucocerebrosidase in leukocytes or fibroblasts and genetic testing. An effective therapy for Gaucher disease has now been available for more than 10 years. It consists of life-long intravenous replacement of the deficient enzyme--glucocerebrosidase. If enzyme replacement therapy is started early enough, it leads to significant improvement in patient's general condition and quality of life. The aim of this document is to provide to the Croatian medical audience the guidelines for diagnosis and management of adult patients with Gaucher disease. These guidelines are produced by specialists who have long lasting experience with patients with rare metabolic diseases working in the Division of Metabolic Diseases, Department of Internal Medicine, University Hospital Center Zagreb which is the Referral Center for Rare and Metabolic diseases of the Ministry of Health, Republic of Croatia. They were endorsed by the Croatian Society for Rare Diseases, Croatian Medical Association. These are the first guidelines published in Croatia on diagnosis, treatment and follow-up of Gaucher disease.
Asunto(s)
Enfermedad de Gaucher/diagnóstico , Enfermedad de Gaucher/terapia , Guías de Práctica Clínica como Asunto , Adulto , Algoritmos , Croacia , Femenino , Enfermedad de Gaucher/prevención & control , Glucosilceramidasa/administración & dosificación , Humanos , Medicina Interna/normas , Relaciones Interprofesionales , Persona de Mediana Edad , Examen Neurológico , Calidad de Vida , Sociedades Médicas/normasRESUMEN
Early diagnosis and management of patients with Fabry disease (FD) requires a multidisciplinary approach of several different experts. The aim of this document is to provide health care professionals with guidelines for management of adult patients with Fabry disease. These guidelines were produced by the staff of the Division of Metabolic Diseases, Department of Internal Medicine, University Hospital Center Zagreb, which is the Referral Expert Center for Rare and Metabolic Diseases of the Ministry of Health, Republic of Croatia. The first guidelines ever published in Croatia concerning a rare metabolic disease are presented. This document provides a short summary on Fabry disease, how to diagnose Fabry disease, management of patients with this disease, follow-up of the patients, and gives recommendations on therapy and genetic testing.
Asunto(s)
Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/terapia , Asesoramiento Genético/métodos , Guías de Práctica Clínica como Asunto , Adulto , Croacia , Enfermedad de Fabry/genética , Pruebas Genéticas , Humanos , Relaciones Interprofesionales , Isoenzimas/uso terapéutico , Esperanza de Vida , Calidad de Vida , Sociedades Médicas/normas , alfa-Galactosidasa/uso terapéuticoRESUMEN
The clinical picture of classical homocystinuria is diverse. This is the first report of an adult homocystinuric patient with non-traumatic spontaneous small bowel perforation. A 47-year old man presented with abdominal rebound tenderness, hypotension and tachycardia, anemia, and elevated markers of inflammation. Other routine laboratory tests were normal. Abdominal x-ray showed no free air. An emergency laparotomy revealed jejunal perforation in the left upper quadrant. Histologic specimen showed full-thickness nonspecific inflammation of the intestinal wall with granulocytic infiltration, hemorrhage and necrosis. Tuberculosis, actinomycosis and typhus were histologically and clinically excluded. After excluding all known possible causes of perforation, we presumed a causative relationship between homocystinuria and small bowel perforation. It could be hypothesized that connective tissue weakness in homocystinuria is a result of homocysteine interference with recombinant human fibrillin-1 fragments or cross-linking of collagen through permanent degradation of disulfide bridges and lysine amino acid residues in proteins. DNA analysis showed three detectable mutations in the cystathionine beta-synthetase gene, 1278T:c.833T>C, and two new mutations, V372G:c.1133T > G, and D520G:c.1558A > G in the aternatively spliced exon 15.
Asunto(s)
Cistationina betasintasa/genética , Homocistinuria/patología , Perforación Intestinal/patología , Homocistinuria/enzimología , Homocistinuria/genética , Humanos , Perforación Intestinal/sangre , Masculino , Persona de Mediana Edad , Mutación , NecrosisRESUMEN
FINDINGS: BMI was increased (>25) in 22% of young healthy subjects. Increased cholesterol values (>5.0 mmol/L) were found in 23% of subjects, LDL-C (>3.0 mmol/L) in 23%, triglycerides (>1.7 mmol/L) in 11% of subjects. We found statistically significant differences in subjects' weight (p = 0.015), BMI (p = 0.023), and waist-hip ratio (WHR) (p = 0.015) in regard to their diet type; subjects with Mediterranean diet had the lowest values compared to those on continental and mixed diet. Significant associations were found for: LPL genetic polymorphic variant and abdominal obesity (p = 0.013), APO epsilon4 allele and hypercholesterolemia (p = 0.003), and ESR1-TA long allele and hypercholesterolemia (p = 0.011). BACKGROUND: Human obesity is a multifactorial syndrome influenced also by genetic factors. Among gene variants found to be involved in body weight regulation and development of obesity, particular attention has been paid to polymorphisms in genes associated with obesity-related metabolic disorders. We explored the association of genetic polymorphisms of: estrogen receptor alpha (ESR1-TA repeats); interleukin-6 (IL-6 G-174C); apolipoprotein E (APO epsilon2, epsilon3, epsilon4); lipoprotein lipase Pvu II (LPL P+/-), with clinical variables: gender, age, body mass index (BMI), diet type and biological variables: triglycerides, cholesterol, HDL-C, LDL-C, CRP, homocysteine, urate, and glucose in 105 healthy young subjects (20-35 yrs) of Croatian origin. METHODS: Genotyping of IL-6, LPL was performed by PCR-RFLP, of APOE by real-time PCR, and of ESR1 by PCR and capillary electrophoresis. Association analyses were performed of alleles and genotypes with biological variables. CONCLUSION: ESR-1, LPL, and APO E genetic polymorphic variants could represent predictive genetic risk markers for obesity-related metabolic disorders in young healthy subjects. Mediterranean type of diet is also an important protective factor against abdominal obesity.
RESUMEN
Hyperlipidaemia and diabetes are among the major risk factors for cardiovascular diseases (CVD). The incidence of CVD, as evidenced by the respective mean incident rate for each of the risk factor, is quite high throughout the European countries. Of late, these risk factors for CVD, especially for hyperlipidaemia and diabetes are setting in at an alarming rate in many of the low- and medium-income countries also, particularly among their urban populations. Therefore, planning and implementing programmes for prevention of CVD, particularly for controlling risk factors like hyperlipidaemia and diabetes should be accorded high priority.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus/tratamiento farmacológico , Hiperlipidemias/tratamiento farmacológico , Enfermedades Cardiovasculares/etiología , Enfermedad Coronaria/etiología , Enfermedad Coronaria/prevención & control , Humanos , Hiperlipidemias/complicaciones , Infarto del Miocardio/etiología , Infarto del Miocardio/prevención & control , Factores de RiesgoRESUMEN
Thrombotic thrombocytopenic purpura (TTP) either occurs in a congenital form caused by ADAMTS13 gene mutations or it is acquired and most often due to ADAMTS13 inhibitory autoantibodies. In congenital TTP siblings are often affected, while acquired TTP occurs sporadically and familial clustering has not been described so far. We report identical twin sisters suffering from acquired TTP due to immunoglobulin G (IgG) autoantibodies inactivating ADAMTS13, suggesting an important role of hitherto unidentified genetic determinants of ADAMTS13 inhibitor formation. These cases also demonstrate that familial clustering is not sufficient for unambiguously diagnosing hereditary ADAMTS13 deficiency and congenital TTP.
Asunto(s)
Metaloendopeptidasas/genética , Metaloendopeptidasas/inmunología , Púrpura Trombocitopénica Trombótica/genética , Púrpura Trombocitopénica Trombótica/inmunología , Proteínas ADAM , Proteína ADAMTS13 , Adulto , Autoanticuerpos/sangre , Femenino , Prueba de Histocompatibilidad , Humanos , Metaloendopeptidasas/deficiencia , Gemelos Monocigóticos/genéticaRESUMEN
Although at present there is no prospective randomized study which could show significantly better survival of patients on continuous procedures, the majority of intensivists advocate this technique of renal function replacement due to generally accepted opinion that it has less effect on circulation of already hemodynamically unstable patients. In our prospective randomized study with 104 patients, we also did not observe any difference in 28 days survival, in total survival, as well as in circulatory instability between two treatment modalities. Even in subgroup of 80 patients with sepsis and septic shock there were no difference in survival. Sepsis was the underlying disorder in 52 and septic shock in 28 patients out of 104 patients analyzed in this study. Our prospective randomized study did not show a statistically significant difference between the two methods of renal replacement therapy. Survival rates were not affected and neither was the occurrence of hemodynamic instability. We believe that both methods are complementary; IHD for faster elimination of electrolytes and waste products elimination, CRRT for regulation of higher calories requirements and for hemodynamically unstable patients. The expectations that one method is superior to the other in the term of better survival have not been corroborated by the current data available in the literature. The choice of the method should be individualized. ARF, which is an integral part of MOF, is a problem frequently encountered in critically ill patient treated in the ICU, but outcome of these patients depends closely on the control of basic event. Evaluation of each of the supportive procedures is therefore hindered by the fact that the underlying disease has the crucial effect on survival and the type of supportive procedure less so.
Asunto(s)
Lesión Renal Aguda/terapia , Cuidados Críticos/métodos , Terapia de Reemplazo Renal/métodos , Lesión Renal Aguda/complicaciones , Enfermedad Crítica , Humanos , Insuficiencia Multiorgánica/complicaciones , Estudios Prospectivos , Diálisis Renal/métodos , Sepsis/complicaciones , Índice de Severidad de la Enfermedad , Análisis de SupervivenciaRESUMEN
UNLABELLED: Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are classical diseases characterized by thrombocytopenia and microangiopathic hemolytic anemia. Microangiopathic hemolytic anemia is also a part of clinical picture in patients with hemorrhagic fever with renal syndrome (HFRS). Some overlap in other elements of clinical picture between TTP and HFRS is possible, which could pose difficulties in differential diagnosis. Early treatment of patients with TTP is essential and significantly improves the outcome, whereas the treatment of HFRS is mainly supportive. In the last ten years, we treated 13 patients with TTP and 17 patients with HFRS. Two patients with HFRS were initially treated as TTP because it was not possible to exclude TTP on the basis of clinical picture. Further clinical course and serologic tests excluded TTP and suggested HFRS. CONCLUSION: Sometimes it is difficult to distinguish HFRS from TTP because thrombocytopenia and microangiopathic hemolytic anemia are present in both diseases and overlaps in other parts of clinical picture are possible. The serious consequences of delay in the efficacious treatment of patients with TTP could also influence the physicians' decisions.