RESUMO
INTRODUCTION: Numerous professional groups and sections for the medical specialities have been organized since 1953 in the West-Transdanubian region of Hungary, but such association of neurologists had not occured. ESTABLISHING THE WEST-PANNONIC NEUROLOGICAL FORUM: The lack of regional collaboration among neurologists was related to several factors, among which the most important factor was the lack of a regional medical university, which could coordinate the professional activities. This severe gap necessitated in 1998 the organization of a professional group, that has become a driver for case-consulting conferences and different postgraduate trainings for the physicians specialized in neurology, neurosurgery and neurorehabilitation in counties of Gyor-Moson-Sopron, Vas, Veszpr6m and Zala. THE FUNCTIONING OF THE FORUM: Meetings are organized twice a year for physicians and paramedical staff (nurses, hospital attendants, physiotherapists) on Thursdays afternoons in different towns of the region, in two sections. The lectures are followed by a buffet, after which everyone can get home before too late. Ocasionally guest-lecturers are invited to present scientific topics from Hungarian universities or abroad. However, the main form of the presentations is defined as case discussion. CONCLUSIONS: The numbers of platform and other presentations in the physicians's section have exceeded half a thousand, while in the paramedical section reached the three- hundreds. At the 38. meeting of the Forum in January of this year, the number of participants was more than two-hundreds, reflecting that both physicians and their coworkers are greatly interested in this form of interactions.
Assuntos
Pessoal Técnico de Saúde , Congressos como Assunto , Reabilitação Neurológica , Neurologia , Neurocirurgia , Médicos , Humanos , Hungria , Encaminhamento e ConsultaRESUMO
We carried out molecular studies of 15 unrelated Hungarian families diagnosed with Fabry disease (FD). Genetic analysis of the alpha-galactosidase A gene was performed in 22 hemizygous males and 34 females. One of the female patients with severe disease phenotype showed homozygosity for the recurrent c.644A>G mutation due to parental consanguinity. The c.644A>G mutation that has previously been found mostly in patients with the cardiac variant of FD, was associated with renal but not cardiac involvement in this female and in two other family members. In nine families, eight novel sequence variants such as small deletions (c.363delT, c.477delT, c.746delAC) and single nucleotide changes (c.107T>C, c.493G>C, c.796G>T, c.866T>G, c.871G>A) were found in addition to six previously described private mutations. This report contributes to the identification of novel disease-causing mutations in FD, and increases our knowledge on demographics and molecular characteristics of this rare lysosomal storage disorder. This is the first comprehensive overview of molecular genetic features of Hungarian patients with FD.
Assuntos
Doença de Fabry/enzimologia , Variação Genética , alfa-Galactosidase/genética , Adolescente , Adulto , Sequência de Bases , Doença de Fabry/genética , Família , Feminino , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Polimorfismo de Fragmento de Restrição , alfa-Galactosidase/metabolismoRESUMO
Fabry disease is a rare, progressive lysosomal storage disorder caused by mutation in the GAL gene and an impaired function of the alpha-galactosidase A enzyme. The enzymatic defect results in the progressive accumulation of glycosphingolipids in endothelial cells, smooth muscle cells, leucocytes and fibroblasts leading to organ damage in the skin, eye, nervous system, kidney and heart. Major clinical manifestations include acroparesthesis, angiokeratoma, corneal opacities, vascular diseases of the heart, kidney, and the central nervous system. Enzyme replacement therapy has recently become available for the treatment of Fabry patients. In this review the authors describe clinical features of Fabry disease in 31 Hungarian patients. At the time of this analysis the database consisted of 31 cases (15 males, 16 females) of whom 5 have died (4 males, 1 female). The most common disease-specific manifestation was angiokeratoma in males, and eye symptoms in females. 25% of female subjects were symptom free. Genotyping was performed in all cases and disease-causing mutations were found in all families. Three new mutations were identified. Twelve patients (8 males and 4 females) are currently receiving enzyme replacement therapy.
Assuntos
Doença de Fabry/diagnóstico , Doença de Fabry/genética , Adolescente , Adulto , Idoso , Angioceratoma/etiologia , Isquemia Encefálica/etiologia , Criança , Pré-Escolar , Doença de Fabry/complicações , Doença de Fabry/patologia , Doença de Fabry/fisiopatologia , Doença de Fabry/terapia , Feminino , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Proteinúria/etiologiaRESUMO
Fabry's disease is an X-linked lysosomal storage disorder. alpha-Galactosidase deficiency leads to accumulation of globotriaosylceramide mainly in endothelial and smooth muscle cells. Cerebrovascular symptoms with predominant affection of the vertebrobasilar circulation are one of the major sources of morbidity in Fabry's disease. We present a Hungarian family with Fabry's disease caused by a new mutation in the alpha-galactosidase A gene (GLA), and describe a variant expression of the disease. Megadolichobasilar anomaly was diagnosed in two male patients in the family who died of thrombosis. In another female patient who had suffered from disturbance of the vertebrobasilar circulation, a strongly dilated basilar artery without thrombosis was found at autopsy. Another three family members had basilar strokes and large and elongated basilar arteries on MRI. Genetic analysis disclosed a c.47T-->C missense mutation resulting in L16P in the amino acid sequence of the alpha-galactosidase protein. This report suggests that megadolichobasilar anomaly is potentially life-threatening, and that L16P is a disease-causing mutation in patients with Fabry's disease. Early enzyme replacement therapy may prevent the development of these irreversible cerebrovascular complications.