Gábor Mogyorósy

Phenotypic manifestations of the OCTN2 V295X mutation: sudden infant death and carnitine-responsive cardiomyopathy in Roma families.

In two non‐consanguineous Hungarian Roma (Gypsy) children who presented with cardiomyopathy and decreased plasma carnitine levels, we identified homozygous deletion of 17081C of the SLC22A5 gene that results in a frameshift at R282D and leads ultimately to a premature stop codon (V295X) in the OCTN2 carnitine transporter. Carnitine treatment resulted in dramatic improvement of the cardiac symptoms, echocardiographic, and EKG findings in both cases. Family investigations revealed four sudden deaths, two of them corresponded to the classic SIDS phenotype. In postmortem tissue specimens available from three of them we could verify the homozygous mutation. In liver tissue reserved from two patients lipid droplet vacuolization could be observed; the lipid vacuoles were located mainly in the peripherolobular regions of the acini. In the heart tissue signs of generalized hypertrophy and lipid vacuoles were seen predominantly in the subendocardial areas in both cases; some aggregates of smaller lipid vacuoles were separated, apparently by membranes. Review of all OCTN2 deficiency cases reported so far revealed that this is the first presentation of histopathology in classic familial sudden infant death syndrome (SIDS) with an established SLC22A5 mutation. In addition to the two affected homozygous cardiomyopathic children and three homozygous sudden death patients, the genetic analysis in 25 relatives showed 14 carriers. The mutant gene derived from five non‐consanguineous grandparents, each of them having 6–14 brothers and sisters. This alone suggests a wide ancestral spread of the mutation in certain Roma subpopulations.

Measuring health-related quality of life in Hungarian children with heart disease: psychometric properties of the Hungarian version of the Pediatric Quality of Life Inventory 4.0 Generic Core Scales and the Cardiac Module.

ObjectivesThe aim of the study was to investigate the psychometric properties of the Hungarian version of the Pediatric Quality of Life Inventory™ (PedsQL™) Generic Core Scales and Cardiac Module.MethodsThe PedsQL™ 4.0 Generic Core Scales and the PedsQL™ 3.0 Cardiac Module was administered to 254 caregivers of children (aged 2-18 years) and to 195 children (aged 5-18 years) at a pediatric cardiology outpatient unit. A postal survey on a demographically group-matched sample of the general population with 525 caregivers of children (aged 2-18 years) and 373 children (aged 5-18 years) was conducted with the PedsQL™ 4.0 Generic Core Scale. Responses were described, compared over subgroups of subjects, and were used to assess practical utility, distributional coverage, construct validity, internal consistency, and inter-reporter agreement of the instrument.ResultsThe moderate scale-level mean percentage of missing item responses (range 1.8-2.3%) supported the feasibility of the Generic Core Scales for general Hungarian children. Minimal to moderate ceiling effects and no floor effects were found on the Generic Core Scales. We observed stronger ceiling than floor effects in the Cardiac Module. Most of the scales showed satisfactory reliability with Cronbachs α estimates exceeding 0.70. Generally, moderate to good agreement was found between self- and parent proxy-reports in the patient and in the comparison group (intraclass correlation coefficient range 0.52-0.77), but remarkably low agreement in the perceived physical appearance subscale in the age group 5-7 years (0.18) and for the treatment II scale (problems on taking heart medicine) scale of the Cardiac Module in children aged 8-12 years (0.39). Assessing the construct validity of the questionnaires, statistically significant difference was found between the patient group and the comparison group only in the Physical Functioning Scale scores (p = 0.003) of the child self-report component, and in Physical (p = 0.022), Emotional, (p = 0.017), Psychosocial Summary (p = 0.019) scores and in the total HRQoL (health-related quality of life) scale score (p = 0.034) for parent proxy-report.ConclusionThe findings generally support the feasibility, reliability and validity of the Hungarian translation of the PedsQL™ 4.0 Generic Core Scales and the PedsQL™ 3.0 Cardiac Module in Hungarian children with heart disease.

Candida endocarditis in a premature infant

Abstract Endocarditis is an uncommon complication of invasive candidiasis. We present a fatal case of endocarditis caused by Candida albicans in a very low birth weight infant. The 780-g male infant did not have any structural heart disease and a central venous catheter was not placed. Endocarditis developed in spite of parenteral fluconazole treatment. Echocardiography was a valuable tool in making the diagnosis. The infant died on the 40th day of life. The development of Candida endocarditis in a premature infant who was treated with fluconazole had not been previously reported. In the case of systemic candidiasis, premature infants require very careful monitoring for the progression of the disease, even if antifungal therapy is administered.

Hungarian validation of the cardiac module of the Pediatric Quality of Life Inventory

UNLABELLED The authors report the validation process of the cardiac module of the Pediatric Quality of Life Inventory (PedsQL ) into Hungarian. BACKGROUND The PedsQL which is a modular instrument to evaluate health-related quality of life (HRQL ) in children and adolescents of ages 2-18 years, comes up to the current professional requirements at a high level. There is no report on health-related quality of life measure in Hungary which was performed among children with heart disease. OBJECTIVE To adapt and to test a pediatric quality of life questionnaire for measuring HRQL in children with heart disease. METHODS Sequential validation process which follows international guidelines. Pilot-study on 105 children with heart disease. RESULTS According to the results of the pilot-study the psychic domains have a negative influence on general HRQL index in both child and parent-proxy reports in all age groups. On the cardiac module parents of children of all age groups but only children of ages 5-7 years reported marked treatment anxiety. Cognitive and communication problems are mainly important for children of ages 8-18 years. Parent-child concordance is depending on the age of the child, there was expressed difference in the psychosocial domains. We have found no negative effect of heart operation on HRQL by itself but taking medicine may impair it. CONCLUSION Further methodologic research should evaluate the psychometric properties of the newly validated Hungarian version of the PedsQL cardiac module. The detailed report about the validation process can help in the spreading of patient reported outcome measures in Hungary.

Principles of quality of life measurement and its application in childhood

BACKGROUND The evaluative and critical analysis of articles on the quality of life which appear in growing number in the medical literature, and the adaptation of the measures to clinical practice can be realised only through knowledge of the professional standards of the measuring methods. OBJECTIVE To outline the most widely accepted definitions of life- and health-related quality of life, to define the application possibilities as well as the parameters of the measuring methods. To demonstrate the most common problems as well as the possibilities of implementing pediatric measures. To give concrete guidance on evaluating previous measures and designing new ones. METHOD Through a review of literature on methodology, cultural equivalence and paediatric measures, the authors outline the most frequent problems and give examples of some methods corresponding to the current professional standards. CONCLUSION The quality of health care can be improved by using patient-reported outcome measures such as health-related quality of life measures. To assess different patient groups, modular approaches with general and disease-specific modules are advisable. The linguistic and cultural equivalence and the international comparability of the results can be achieved by adhering to professional guidelines and by performing psychometric tests to control the parameters of the methodology. In paediatric measures efforts should be made to conduct the simultaneous questioning of children and their parents as early as possible.

Critical appraisal of articles about clinical audit

OBJECTIVE To summarize the most important criteria used in critical appraisal of publications about clinical audit by the review of the relevant English language literature. METHODS Electronic databases, including Medline, Science Direct, and Ingenta Select, and Internet search were used to find relevant English language publication between 1985 and 2005. Hand search and the reference lists search for publications were also applied. In addition, researchers were also contacted for publications. RESULTS The literature is surprisingly scarce about the critical appraisal of clinical audit publications. As a result hand search was as important as electronic search. The following three screening criteria can be used in order to critically appraise the scientific literature: (a) whether or not valid and relevant criteria and standards were used to evaluate clinical practice, (b) the criteria were used systematically on a representative sample of patients, and (c) the results are important and applicable (generalizable) in our practice. The publication is useful if it helps to improve the quality of our own clinical practice. CONCLUSION Critical appraisal criteria can be used to improve the quality of clinical audit, and disseminate the results of audit, as well as find high quality evidence for designing and implementing quality improvement initiatives.

Pediatric myocarditis: A sentinel of non-cardiac chronic diseases?

INTRODUCTION Although long-term outcome studies in large pediatric myocarditis/cardiomyopathy populations have been reported in literature, none of them focused on comorbidities. METHODS All children and adolescents (age <18 years) treated with myocarditis at the Department of Pediatrics, University of Debrecen, Hungary were followed. Patients suffering from myocarditis during the period 1996-2011 were enrolled. RESULTS Over the 16-year period, a diagnosis of myocarditis was established in nine children. Their median age was 1.11 (0.03-8.71) years. Three of the nine patients died. Left ventricular dilatation and ejection fraction normalized within 1-21 months in the survivors. None of the cases progressed to dilated cardiomyopathy. Regarding non-cardiac comorbidities, myocarditis or recurrent peri-myocarditis preceded the manifestation of celiac disease in two patients, while cystic fibrosis was diagnosed after the improvement of cardiac function in another, and Alström syndrome was diagnosed several years after complete recovery from myocarditis in yet another patient. CONCLUSION These results suggest that manifestations of other chronic pediatric diseases may be more frequent among survivors of pediatric myocarditis. Prolonged follow-up of patients who survive myocarditis is therefore recommended not only to detect possible progression to cardiomyopathy but also to identify non-cardiac comorbidities.

Molecular pathology and clinical manifestations of Fabry disease

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.

Szisztematikus irodalmi áttekintések módszertana és jelentősége. Segítség a diagnosztikus és terápiás döntésekhez

There is no proven effective treatment for many diseases today that proves to be one of the greatest problems of health care. Therefore, different therapeutic decisions are made in connection with the same disease by hospitals. There is a growing need for reviews which summarize the information collected from professional literature with scientific methods. The aim of the authors was to show the limitations of conventional narrative reviews, and to present the method and importance of systematic reviews to Hungarian professionals. Systematic reviews are transparent studies which are based on a predetermined protocol and collate all empirical evidence to answer a specific research question, and consequently provide more reliable results. They use explicit and systematic methods to minimize bias, and provide evidence for clinicians and policy makers to help them make diagnostic and therapeutic decisions which are essential in several fields of the health care system and health policy, too.

Deletion 15q26 syndrome

The association of short stature, microcephaly, congenital cardiac anomaly and intellectual deficit should always raise the suspicion of chromosomal etiology. If G-banded karyotyping fails to detect large chromosomal aberrations, array comparative genomic hybridization (array CGH) should be performed to screen for submicroscopic pathological copy number changes. The authors present a six-year-old girl whose symptoms arose from a 4.1 Mb loss in the 15q26.2-26.3 telomeric region. The syndrome is characterized by a resistance to the insulin-like growth factor 1 - in our case the increased level of the insulin-like growth factor 1 together with the persistent longitudinal growth failure was an important finding and differential diagnostic feature. A brief overview of the literature is provided.