We analysed the clinical history of 16 hemizygous males affected by Anderson‐Fabry Disease, from four families, to verify their intrafamilial phenotypic variability. Seven male patients, ranging from 26 to 61 years of age, died, whereas nine (age range 23–55) are alive. Eleven patients have undergone enzyme replacement therapy (ERT) for a period of 5–10 years. We have found a wide range of intrafamilial phenotypic variability in these families, both in terms of target‐organs and severity of the disease. Overall, our findings confirm previous data from the literature showing a high degree of intrafamilial phenotypic variability in patients carrying the same mutation. Furthermore, our results underscore the difficulty in giving accurate prognostic information to patients during genetic counselling, both in terms of rate of disease progression and involvement of different organs, when such prognosis is solely based on the patient's family history.

AIM:To assess the effects of enzyme replacement therapy (ERT) in children with Fabry disease.METHODS:Safety and efficacy of ERT with agalsidase alfa, 0.2 mg/kg infused over 40 minutes every 2 weeks for 23 weeks, were studied in a multicentre open-label trial in nine boys and four girls. Median age at the start of the study was 11.0 years (range 3.5-18 years).RESULTS:Fifty-four adverse events were reported in 11 patients. No serious adverse events related to ERT were reported. Twelve of the 54 adverse events were considered possibly or probably related to ERT. Infusion reactions (8 mild, 3 moderate) occurred in four boys, in seven infusions. One boy developed IgG antibodies, although he continued to make good clinical progress. At the end of the study, two of the four boys and the one girl on regular pain medication at baseline had stopped taking analgesics. Brief Pain Inventory (BPI) scores decreased in most patients by week 12 and were sustained until the end of the study. This change was greater in the boys, who had higher (worse) BPI scores at baseline. Pain-related quality of life (QoL) scores also decreased during the study. Plasma globotriaosylceramide concentrations and urinary globotriaosylceramide:sphingomyelin ratios decreased after 12 and 23 weeks of therapy, particularly in the boys. Increases in sweat volume were recorded in three out of five of the boys and in one of two girls tested after 23 weeks of treatment.CONCLUSION:ERT with agalsidase alfa in children with Fabry disease is well tolerated and, in the short term, appears to decrease pain and to improve pain-related QoL.

Anderson-Fabry disease (AFD) is a rare X-linked disorder caused by lysosomal storage of several glycosphingolipids, affecting virtually all organs and systems. Enzyme replacement therapy (ERT) for AFD has been available since 2001. Due to the highly variable nature of clinical manifestations in patients with AFD, it is very difficult to assess disease progression and the effects of therapy. We used the Mainz Severity Score Index (MSSI) as a measure of disease severity to study the effects of ERT in a population of 30 patients treated with agalsidase alfa for a median of 2.9 years (range, 1.0-6.2 years). Our data show that the MSSI captures the correlation between disease severity and both gender and age (1 - males performing worse than females at baseline and 2 - severity of diseases progresses with age in both sex). Furthermore, after at least 1 year of ERT, total MSSI scores were significantly lower than those at baseline (p < 0.001), suggesting a marked clinical improvement under ERT. In conclusion, the MSSI is a sensitive and useful tool for monitoring disease progression and assessing the effects of ERT in a population of patients from different treatment centres.

Aim: To assess the effects of enzyme replacement therapy (ERT) in children with Fabry disease.

Summary A patient with early bilateral nuclear cataracts and subsequent diagnosis of Fanconi–Bickel syndrome is described. Despite impaired galactose and glucose metabolism, cataracts have been reported in only few cases with this disorder. We conclude that Fanconi–Bickel syndrome should be considered in the differential diagnosis of neonatal cataracts. The pathogenesis of this complication has not been fully elucidated.

Aims: Evaluation of the effects of alfa-L iduronidase in 6 Italian MPS I patients. Patients and Methods: 6 pts (2 MPS IH/S and 4 MPS IS) mean age 24 yrs (range 11–38 yrs) received ERT 100 U/kg/week for 18.7 month mean (range 4–33 ms). We tested urinary glycosaminoglycans (GAGs), heart function, splenomegaly, joint function and quality of life (QoL). Results: only one patient had an adverse reaction (severe urticaria) and it was necessary to reduce the dosage to 80 U/Kg/week. Results in the 3 MPS IS and 2 MPS I HS treated with a mean follow-up of 19,2 ms (range 12–30 ms) are the following: reduction in urinary GAGs excretion (-78 % mean; range -50%-91%), in bipolar diameter of the spleen (mean 1.2 cm, range 0 − 4 cm); cardiac parameters stabilised. Improvement of joint mobility with a maximum of 30 for shoulder abduction. Improvement of QoL in one MPS IS (30 ms treatment), especially in dressing herself and in the daily care; no improvement in QoL in the other two MPS IS after one year, although their joint mobility became better. Parents of the two pts affected by MPS HIS noted a stabilisation in one case and an improvement in the other in the daily care. Conclusions: ERT led, as expected, to a reduction of urinary GAGs excretion, splenomegaly, and improvement of joint mobility. The improvement of the QoL was clear in only 1/5 pts. Probably, for the less severe forms of MPS IS a longer follow up is needed to appreciate an improvement, while, on the other side in MPS I HS pts, severe disability could heavily influence the quality of life and the autonomy, hiding the benefits of an increased joint mobility.