A family with various symptomatology suggestive of Anderson-Fabry disease and a genetic polymorphism of alpha galactosidase A gene.

BACKGROUND: Anderson/Fabry disease expresses a wide range of clinical variability in patients that it is possible to explain referring to a genetic variability with numerous mutations described in the literature (more than 600). METHODS: We report some clinical cases of some members of a Sicilian family to express phenotypical variability of this disease in subjects with the same genetic mutation RESULTS: The first case was a 59-year-old female. Brain MRI revealed right frontal periventricular white matter of likely vascular-degenerative origin. The proband's alpha galactosidase A activity was 3.7nmol/mL/h. Molecular genetics revealed a polymorphism: -10 C>T; IVS 2-76_80del5; IVS4-16 A>G; IVS6-22 C>T. The second case was a 30year-old male affected by acroparesthesias and hypoidrosis since he was an adolescent. Renal impairment was first detected at age 29; it began with high plasma levels of creatinine and microalbuminuria date. The third case was a 41year-old daughter that presented with acroparesthesias, hypoidrosis since she was very young. The patient's alpha galactosidase A activity was 4.1nmol/mL/h, in whole blood, which is compatible with heterozygote subject for Fabry's disease or healthy control. The fourth case was a male grandson of the proband, 9year-old child. He had a classic gastrointestinal involvement. He complained of recurrent abdominal pain, post prandial bloating and pain. This child's enzyme activity was 1.65nmol/mL/h. In cases 2, 3, and 4, molecular genetics revealed a polymorphism: -10 C>T; IVS 2-76_80del5; IVS4-16 A>G; IVS6-22 CG, IVS6-22C>T polymorphisms occurred in 8.9% and 3.7% of the subjects respectively, and the significance of this haplotype in FD pathology remains unknown but possibly suggestive of Anderson/Fabry disease.

Fast recovery with etanercept in patients affected by polymyalgia rheumatica and decompensated diabetes: a case-series study.

We enrolled nine consecutive patients affected by newly diagnosed polymyalgia rheumatica and decompensated diabetes mellitus. All patients were treated with etanercept (25 mg twice weekly) and prednisone and were followed up to 1 year. At the sixth-month follow-up, etanercept and prednisone were withdrawn. Patients were seen at regular intervals (days 0, 30, 60, 90, 150, 180) and the following variables determined: erythrocytes sedimentation rate, C-reactive protein, fasting serum glucose, pain measured by visual analog scale, and the Health Assessment Questionnaire. Our results indicate that etanercept might have some steroid-sparing effects, but controlled investigations are needed to support etanercept use in clinical practice for this kind of patients.

Safety of etanercept therapy in rheumatoid patients undergoing surgery: preliminary report.

This is a preliminary report on a case-series of rheumatoid patients that underwent various kinds of elective surgery but did not withdraw etanercept therapy in spite of physician advise. Elective surgery consisted of right knee surgical prosthesis, bilateral cataract, bilateral hallux valgus, right hip prosthesis, bladder stone by cystoscopy and left inguinal hernia. All the patients had a regular healing rate. During follow-up (6-12 months) no one of these patients were suffering from infective complications after surgery. According to same recent literature results, our data suggest that it is the time to value rheumatoid patient preferences through a correct information about cost-benefit of this treatment to establish together with patients if etanercept therapy has to be discontinued before and after elective surgery. Finally, we think that adverse drug reaction surveillance has to be boosted, and editors of leading scientific journal should publish more papers on case-series about drug safety and tolerability in particular conditions.