[Fabry disease--diagnostic guideline]. / Fabry-betegség. Diagnosztikai útmutató.

Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive, first symptoms usually present in childhood. Consequencies of the diseases are disability and premature death. The disease in females could be as severe as in males although women may also be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline was established by a Hungarian multi-disciplinary working group, consisting of physicians who are involved in health care of Fabry patients. Previous clinical studies, published materials, and recently established international treatment guidelines were reviewed by the group.

[Management of Fabry disease]. / Fabry-betegség - terápiás útmutató

Fabry disease is a rare, X-linked lysosomal storage disorder that leads to accumulation of globotriaosylceramide in different tissues of the body. The disease is progressive and the first symptoms usually present in childhood. Consequences of the disease are disability and premature death. The disease in females could be as severe as in males although women may be asymptomatic. The possibility of enzyme replacement therapy has made it necessary to elaborate a comprehensive guideline for the diagnosis and treatment follow-up. The guideline has been summarized by a Hungarian multi-disciplinary working group consisting of physicians who are involved in diagnosis and care of Fabry patients. Previous clinical studies, published articles, and recently established international treatment guidelines were reviewed by the group.

Truncation of retinoschisin protein associated with a novel splice site mutation in the RS1 gene.

PURPOSE: To present the ocular findings of a Hungarian family with X-linked juvenile retinoschisis (XLRS) and to reveal a novel putative splice mutation leading to serious truncation of retinoschisin (RS1) protein. Our genetic results were compared to a mouse model of XLRS. METHODS: Complete ophthalmic examinations were performed on five members (two male patients, two female carriers, and one healthy fraternal male twin) of the family. The examinations included optical coherence tomography (OCT) and full-field and multifocal electroretinography (mfERG). OCT and ERG results were compared to the normative database of our laboratory. All exons and the flanking intronic regions of the RS1 gene were amplified by polymerase chain reaction and directly sequenced in all family members and in 50 male controls. RESULTS: Typical microcystic foveal changes were found on fundoscopy and OCT in two male patients. Large foveal and smaller perifoveal cysts were detected by OCT in the inner nuclear layer and another deeper retinal cleavage in the photoreceptor layer. The standard combined b-wave amplitudes and b/a amplitude ratios of full-field ERGs of the male patients were decreased compared with controls, but the typical "negative-type" ERG was not observed. The amplitudes of mfERGs were reduced in all rings but mainly in the central part of the examined retina. Implicit times were delayed across almost the whole testing field. Female carriers and the healthy fraternal twin brother were without any symptoms and had normal clinical examination results, but the implicit times of female carriers were delayed in all rings. DNA sequence analyses revealed a novel putative splice mutation (c.78+1G>C) in the splice donor site of intron 2 in RS1 of two male patients and two female carriers. Mutations were absent in the 50 control samples. CONCLUSIONS: Male patients exhibited typical bilateral foveal retinoschisis in two retinal layers and characteristic ERG changes. The inheritance of the novel putative splice mutation (c.78+1G>C) followed the classic inheritance of an X-linked recessive disease in two male patients and two female obligate carriers. There are two possible ways the c.78+1G>C splice site mutation may lead to frameshift and introduce a premature termination codon at the beginning of exon 3: after activation of the next cryptic splice site by a 10 bp insertion or after exon skipping by a 26 bp deletion. The splice site mutation in the second intron of RS1 identified in these XLRS patients is practically identical to the N-ethyl-N-nitrosourea (ENU) induced splice site mutation in the mouse model of XLRS described by the Tennessee Mouse Genome Consortium. The genetic findings of the mutant mouse model confirm and support our human results.

Telemedical diabetic retinopathy screening in Hungary: a pilot programme.

Our aim was to introduce the Hungarian pilot telemedical screening program for diabetic retinopathy (DRP) and also to evaluate the efficacy of non-mydriatic fundus photographs. A total of 502 eyes of 251 diabetic patients were photographed with a non-mydriatic digital fundus camera in a tertiary diabetology care center. These three 45°-field images were transmitted to the reading center via Internet, where they were graded by two independent ophthalmologists. After non-mydriatic photography (NM method), 28 patients were also examined in mydriasis by an ophthalmologist (O method) and were also photographed in mydriasis (M method). For the comparison of the three methods the kappa statistic was used. With non-mydriatic imaging of 502 eyes no retinopathy was found in 74.5%, DRP was detected in 15.5%, while 10.1% of the photos were ungradable. The rates of DRP severity levels were: 13.55% mild/moderate non-proliferative, 0.59% severe and 1.39% proliferative DRP. Comparing the results of the gradable non-mydriatic photos by the two independent graders, perfect intergrader agreement was found (k = 1.00). The measure of intermethod agreement between NM and M method was also perfect, with a kappa value of 1.00 (grader A and grader B). Based on the results of the O method, there were no misdiagnosed cases nor with the NM-, neither with the M method. Non-mydriatic cameras could be ideal tools of an extended countrywide retinopathy screening program which may serve to reduce the high prevalence of diabetes-related blindness in Hungary.