Prevalence of thrombophilia and thrombotic events in patients with fabry disease in a Reference Center for Lysosomal Disorders in Southern Brazil

Introduction: Venous thromboembolism (VTE) is a multifactorial genetic disorder that occurs in approximately one in a thousand adults per year. Because there is no laboratory test or clinical marker useful for predicting which patients with Fabry disease may develop thrombotic events, this study aimed to determine whether there is a hereditary predisposition to hypercoagulation in these patients. Methods: The prevalence of p.R506Q mutation in the factor V gene and of c.G20210A mutation in Factor II (prothrombin) gene was evaluated in 39 patients with Fabry disease from Southern Brazil and correlated with clinical findings. The DNA analysis was performed by real-time polymerase chain reaction on genomic DNA using TaqMan probes. Results: In this group of patients, the frequency of mutation in the prothrombin gene was 1.28%, whereas no patient showed mutation in the factor V gene; additionally, there was no correlation between these mutations and the incidence of thrombotic events. Conclusion: Hereditary thrombophilia due to mutations in factor V and prothrombin genes does not seem to be related to thrombotic events in Fabry patients in our cohort, although studies in larger cohorts and the inclusion of additional factors may be required to determine if a correlation exists

Prevalence of thrombophilia and thrombotic events in patients with fabry disease in a Reference Center for Lysosomal Disorders in Southern Brazil

Introduction: Venous thromboembolism (VTE) is a multifactorial genetic disorder that occurs in approximately one in a thousand adults per year. Because there is no laboratory test or clinical marker useful for predicting which patients with Fabry disease may develop thrombotic events, this study aimed to determine whether there is a hereditary predisposition to hypercoagulation in these patients. Methods: The prevalence of p.R506Q mutation in the factor V gene and of c.G20210A mutation in Factor II (prothrombin) gene was evaluated in 39 patients with Fabry disease fromSouthern Brazil and correlated with clinical findings. The DNA analysis was performed by real-time polymerase chain reaction on genomic DNA using TaqMan probes. Results: In this group of patients, the frequency of mutation in the prothrombin gene was 1.28%, whereas no patient showed mutation in the factor V gene; additionally, there was no correlation between these mutations and the incidence of thrombotic events. Conclusion: Hereditary thrombophilia due to mutations in factor V and prothrombin genes does not seem to be related to thrombotic events in Fabry patients in our cohort, although studies in larger cohorts and the inclusion of additional factors may be required to determine if a correlation exists.     Introdução: O tromboembolismo venoso (TEV) é uma desordem genética multifatorial que ocorre em aproximadamente um em cada mil adultos por ano. Pelo fato de não existir nenhum teste de laboratório ou marcador clínico útil para predizer quais pacientes com a doença de Fabry podem desenvolver eventos trombóticos, este estudo foi realizado com o objetivo de determinar se existe uma predisposição hereditária para hipercoagulação nesses pacientes. Métodos: A prevalência da mutação p.R506Q no gene do fator V e da mutação c.G20210A no gene do fator II (protrombina) foi avaliada em 39 pacientes com doença de Fabry do Sul do Brasil e associada com achados clínicos. A análise do DNA genômico foi realizada por reação em cadeia da polimerase (polymerase-chain reaction, PCR) em tempo real utilizando sondas TaqMan. Resultados: Neste grupo de pacientes, a frequência da mutação no gene da protrombina foi de 1,28%, enquanto que nenhum paciente apresentou a mutação no gene do fator V, não havendo correlação entre essas mutações e a incidência de eventos trombóticos. Conclusão: A trombofilia hereditária devido às mutações nos genes fator V e protrombina parece não estar relacionada a eventos trombóticos em pacientes com Fabry em nossa coorte, embora estudos em coortes maiores e a inclusão de fatores adicionais possam ser necessários para determinar se existe uma correlação

Rare disease landscape in Brazil : report of a successful experience in inborn errors of metabolism

Brazil is a country of continental dimensions, with many social inequalities. The latter are reflected on its health system, which comprises a large public component called SUS, a small paid health insurance component and a third very small private component, in which patients pay personally for medical services. Seventy five percent of the population depends on SUS, which thus far does not provide adequate coverage for genetic medical procedures. In 2014, SUS introduced the “Policy for the Integral Attention to Subjects with Rare Diseases”, establishing guidelines for offering diagnosis and treatment. The policy defines the two main axes, genetic and non-genetic rare diseases. In this fashion, public genetic services in SUS will be installed and funded not by themselves, but as part of the more general policy of rare diseases. Unfortunately, up to now this policy is still depending on financial allowances to be effectively launched. In this article, our intention was to describe activities developed in the area of inborn errors of metabolism by a Brazilian reference center. In spite of the lack of support of SUS, thousands of Brazilian families affected by rare genetic metabolic disorders, and many health professionals from all regions of Brazil, already have benefited from the services, training programs and research projects provided by this comprehensive center

Elevated holo-transcobalamin in Gaucher disease type II : a case report

Gaucher disease (GD), one of the most common lysosomal disorders, is caused by deficiency of β-glucocerebrosidase. Based on the presence and severity of neurological complications, GD is classified into types I, II (the most severe form), and III. Abnormalities in systemic markers of vitamin B12 (B12) metabolism have been reported in GD type I patients, suggesting a higher prevalence of B12 deficiency in these patients. A 2-month-old male with GD type II was admitted to the hospital presenting jaundice, hepatosplenomegaly, and ichthyosis. At admission, cholestasis and ascites, abnormal liver function enzymes, prolonged prothrombin time, and high levels of B12 were confirmed. Analysis of biomarkers of B12 status revealed elevated B12 and holo-transcobalamin (holo-TC) levels. The B12 profile found in our patient is the opposite to what is described for GD type I patients. Holo-TC may increase in inflammatory states or due to liver diseases. In GD, the accumulation of glucocerebroside may be a trigger that initiates a systemic inflammatory reaction, characterized by macrophage activation. We suggest higher levels of holo-TC could be associated with a more severe (neuronopathic) GD, and be a biomarker of GD type II

Precision medicine for lysosomal disorders

Precision medicine (PM) is an emerging approach for disease treatment and preventionthat accounts for the individual variability in the genes, environment, and lifestyle of each person.Lysosomal diseases (LDs) are a group of genetic metabolic disorders that include approximately70 monogenic conditions caused by a defect in lysosomal function. LDs may result from primarylysosomal enzyme deficiencies or impairments in membrane-associated proteins, lysosomal enzymeactivators, or modifiers that affect lysosomal function. LDs are heterogeneous disorders, and thephenotype of the affected individual depends on the type of substrate and where it accumulates,which may be impacted by the type of genetic change and residual enzymatic activity. LDs areindividually rare, with a combined incidence of approximately 1:4000 individuals. Specific therapiesare already available for several LDs, and many more are in development. Early identification mayenable disease course prediction and a specific intervention, which is very important for clinicaloutcome. Driven by advances in omics technology, PM aims to provide the most appropriatemanagement for each patient based on the disease susceptibility or treatment response predictionsfor specific subgroups. In this review, we focused on the emerging diagnostic technologies that mayhelp to optimize the management of each LD patient and the therapeutic options available, as well asin clinical developments that enable customized approaches to be selected for each subject, accordingto the principles of PM