La maladie de Fabry chez l'adulte: aspects cliniques et progrès thérapeutiques [Fabry disease in adulthood: clinical aspects and therapeutic progress].

INTRODUCTION: Fabry disease is an X-linked recessive abnormality of glycosphingolipid metabolism that is due to deficiency of the lysosomal enzyme alpha-galactosidase A. CURRENT KNOWLEDGE AND KEY POINTS: A majority of hemizygous men develop severe multisystemic disease (classic form), dominated by renal failure, progressive neurological and cardiac involvement. Nevertheless, some affected men retain sufficient enzyme activity and long remain asymptomatic (atypical form); their main manifestation is hypertrophic cardiomyopathy. Female heterozygous carriers are usually asymptomatic; 15% of them, however, have severe involvement of one or several organs. Laboratory, histologic and molecular diagnosis identifies 100% of hemizygous and over 80% of heterozygous subjects. FUTURE PROSPECTS AND PROJECTS: With developments in molecular genetics, it is now possible to produce the human recombinant enzyme alpha-galactosidase A. Two recent studies had proven that this therapeutic approach was able to be clinically and histologically effective in men. In addition, the results of a trial of gene therapy in a Fabry gene knocked-out mouse appear promising

Prevention of cardiovascular events in end-stage renal disease: results of a randomized trial of fosinopril and implications for future studies

Cardiovascular events (CVEs) are the leading cause of death in chronic hemodialysis patients. Results of trials in non-end-stage renal disease (ESRD) patients cannot be extrapolated to patients with ESRD. It is critical to test cardiovascular therapies in these high-risk patients who are usually excluded from major cardiovascular trials. The study objective was to evaluate the effect of fosinopril on CVEs in patients with ESRD. Eligible patients were randomized to fosinopril 5 mg titrated to 20 mg daily (n=196) or placebo (n=201) plus conventional therapy for 24 months. The primary end point was combined fatal and nonfatal first major CVEs (cardiovascular death, resuscitated death, nonfatal stroke, heart failure, myocardial infarction, or revascularization). No significant benefit for fosinopril was observed in the intent to treat analysis (n=397) after adjusting for independent predictors of CVEs (RR=0.93, 95% confidence interval (CI) 0.68–1.26, P=0.35).Les événements cardiovasculaires (CVEs) sont la principale cause de la mort dans les patients de hémodialyse chroniques. Des résultats des épreuves dans des patients de la maladie rénale d'non-extrémité-étape (ESRD) ne peuvent pas être extrapolés aux patients avec ESRD. Il est critique pour examiner des thérapies cardiovasculaires dans ces patients à haut risque qui sont habituellement exclus des épreuves cardiovasculaires principales. L'objectif d'étude était d'évaluer l'effet du fosinopril sur CVEs dans les patients avec ESRD. Des patients éligibles ont été randomisés au fosinopril 5 titré au 20 (n=196) ou au placebo (n=201) plus la thérapie conventionnelle pendant 24 mois. Le point final primaire était le CVEs principal mortel et non mortel combiné (la mort cardiovasculaire, arrêt du coeur, infarctus du myocarde, ou revascularisation). On n'a observé aucun avantage significatif pour le fosinopril dans cette étude

Evaluation in patients with Alport syndrome of knowledge of the disease and attitudes toward prenatal diagnosis

Cloning of the COL4A5 gene has now made possible prenatal testing for Alport syndrome with X-linked dominant inheritance. We interviewed 27 females and 24 males with Alport syndrome to evaluate their knowledge of the disease and its transmission, and their attitudes to prenatal testing. Twenty-two males and 8 females were on renal replacement therapy. In all cases transmission was compatible with X-linked disease. Only 59% of the interviewees (74% of women, 42% of men) knew that gender was the major determinant in progression of the disease. Knowledge of the mode of inheritance was adequate in only 25%, in both sexes. Seventy percent of the participants (78% of women, 63% of men) would use prenatal testing. Of the women in favor of prenatal diagnosis, 67% and 39% would terminate pregnancy in the case of an affected male or female fetus, respectively. Of the men in favor of prenatal diagnosis, 53% would consider termination of an affected fetus. In summary, a majority would use prenatal testing, but only one or two thirds of them wished to use selective abortion. As in other inherited disorders, there is a discrepancy between the demand for prenatal diagnosis and the decision to terminate pregnancy. Most of the participants who would terminate a pregnancy had, however, little knowledge of the clinical and genetic aspects of Alport syndrome on which to base such a decision. An important aspect of genetic counselling is to assist consultants in reaching a decision regarding future reproductive behaviour which is appropriate to their situation. This study underlines the need to improve education and conselling to assure appropriate use of prenatal testing