Demographic characterization of Brazilian patients enrolled in the Fabry Registry.

Fabry disease (FD) is an X-linked inborn error of metabolism caused by alpha-galactosidase A deficiency. The Fabry Registry is an ongoing observational database that compiles clinical data on patients with FD. We analyzed the Fabry Registry data of patients enrolled in Brazil to characterize the demographic and baseline clinical characteristics of this patient population. As of October 2010, 126 Brazilian patients were enrolled in the Registry (61 males, 65 females). The median age at onset of symptoms in males was 9.8 years, compared to 11.4 years in females. Males were diagnosed at a median age of 31.9 years and females at 27.1 years. The median time between the onset of first symptoms and diagnosis was 20.3 years in males and 14.3 years in females. Neurologic pain was the presenting symptom most frequently reported by both genders. Renal events were the most common clinical events reported in males, while cardiac events were the most common events in females. The results of these analyses indicate that Brazilian patients were frequently not diagnosed with FD until many years after the onset of symptoms. Many Brazilian Fabry Registry patients report experiencing neurological pain, and many Brazilian women with FD exhibit substantial signs and symptoms. The prevalence of neurological pain as a presenting symptom among Brazilian Registry patients is consistent with previous reports from the overall Registry population. FD is treatable, and earlier diagnosis will allow for prompt initiation of appropriate treatment that may avert irreversible damage that could occur during the time from symptom onset to diagnosis.

Demographic characterization of Brazilian patients enrolled in the Fabry Registry

Fabry disease (FD) is an X-linked inborn error of metabolism caused by alpha-galactosidase A deficiency. The Fabry Registry is an ongoing observational database that compiles clinical data on patients with FD. We analyzed the Fabry Registry data of patients enrolled in Brazil to characterize the demographic and baseline clinical characteristics of this patient population. As of October 2010, 126 Brazilian patients were enrolled in the Registry (61 males, 65 females). The median age at onset of symptoms in males was 9.8 years, compared to 11.4 years in females. Males were diagnosed at a median age of 31.9 years and females at 27.1 years. The median time between the onset of first symptoms and diagnosis was 20.3 years in males and 14.3 years in females. Neurologic pain was the presenting symptom most frequently reported by both genders. Renal events were the most common clinical events reported in males, while cardiac events were the most common events in females. The results of these analyses indicate that Brazilian patients were frequently not diagnosed with FD until many years after the onset of symptoms. Many Brazilian Fabry Registry patients report experiencing neurological pain, and many Brazilian women with FD exhibit substantial signs and symptoms. The prevalence of neurological pain as a presenting symptom among Brazilian Registry patients is consistent with previous reports from the overall Registry population. FD is treatable, and earlier diagnosis will allow for prompt initiation of appropriate treatment that may avert irreversible damage that could occur during the time from symptom onset to diagnosis.

Neonatal gene transfer using lentiviral vector for murine Pompe disease: long-term expression and glycogen reduction.

Pompe disease results from the deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to accumulated glycogen in the heart and the skeletal muscles, which causes cardiomyopathy and muscle weakness. In this study, we tested the feasibility of gene therapy for Pompe disease using a lentivirus vector (LV). Newborn GAA knockout mice were treated with intravenous injection of LV encoding human GAA (hGAA) through the facial superficial temporal vein. The transgene expression in the tissues was analyzed up to 24 weeks after treatment. Our results showed that the recombinant LV was efficient not only in increasing the GAA activity in tissues but also in decreasing their glycogen content. The examination of histological sections showed clearence of the glycogen storage in skeletal and cardiac muscles 16 and 24 weeks after a single vector injection. Levels of expressed hGAA could be detected in serum of treated animals until 24 weeks. No significant immune reaction to transgene was detected in most treated animals. Therefore, we show that LV-mediated delivery system was effective in correcting the biochemical abnormalities and that this gene transfer system might be suitable for further studies on delivering GAA to Pompe disease mouse models.