GPI-anchoring disorders and the heart: Is cardiomyopathy an overlooked feature?

Glycosylphosphatidylinositol anchoring disorders (GPI-ADs) are a subgroup of congenital disorders of glycosylation. GPI biosynthesis requires proteins encoded by over 30 genes of which 24 genes are linked to neurodevelopmental disorders. Patients, especially those with PIGA-encephalopathy, have a high risk of premature mortality which sometimes is attributed to cardiomyopathy. We aimed to explore the occurrence of cardiomyopathy among patients with GPI-ADs and to raise awareness about this potentially lethal feature. Unpublished patients with genetically proven GPI-ADs and cardiomyopathy were identified through an international collaboration and recruited through the respective clinicians. We also reviewed the literature for published patients with cardiomyopathy and GPI-AD and contacted the corresponding authors for additional information. We identified four novel and unrelated patients with GPI-AD and cardiomyopathy. Cardiomyopathy was diagnosed before adulthood and was the cause of early demise in two patients. Only one patients underwent cardiac workup after being diagnosed with a GPI-AD. All were diagnosed with PIGA-encephalopathy and three had a disease-causing variant at the same residue. The literature reports five additional children with GPI-AD related cardiomyopathy, three of which died before adulthood. We have shown that patients with GPI-ADs are at risk of developing cardiomyopathy and that regular cardiac workup with echocardiography is necessary.

[CROATIAN POPULATION AND CLINICAL EPIDEMIOLOGICAL STUDIES OF CONGENITAL HEART DISEASE (1995-2011): THE USE OF ABC SCORE AND RACHS-1 CARDIOSURGICAL MODEL FOR THE ASSESSMENT OF QUALITY OF TREATMENT OF CONGENITAL HEART DISEASE]. / HRVATSKE POPULACIJSKE I KLINICKE EPIDEMIOLOSKE STUDIJE PRIROÐENIH SRCANIH GRJESAKA (1995. - 2011.): PRIMJENA POKAZATELJA ABC I KARDIOKIRURSKOG MODELA RACHS-1 ZA PROCJENU KVALITETE ZBRINJAVANJA PRIROÐENIH SRCANIH GRJESAKA.

AIM: 1. To present an epidemiological (population and clinical) study of congenital heart defects (CHD) in Croatia in a 16-year period (1995-2011). 2. To analyze outcomes of surgical procedures for all patients in a five-year period (2002-2007) and to compare the results between Croatian and foreign centers. 3. To present the progress in surgical care of CHD in Croatia while acknowledging the requirement of achieving postsurgical mortality rate of below 5%. 4. To evaluate the projection of positive development of CHD management in Croatia in cooperation with major cardiac surgical centers in the neighboring countries. METHODS: Population study includes all children born from 1995 to 2000 and from 2002 to 2007 included in a database modeled by EUROCAT and BWIS. Outcome analysis was made using two models (ABC and RACHS-1) with early mortality rating and prolonged length of stay. Results: Based on two separate studies, mean value of CHD prevalence in Croatia is 7.6 per thousand. Outcome analysis according to the two mentioned evaluation models for the 2002-2007 period shows that children operated on in Croatia had a lower level of complexity compared to the complexity of those sent to foreign centers, but early mortality was below the assigned margin of 5% and there were also no differences in prolonged length of stay. As much as 63% of surgeries in the period were performed abroad, while the remaining 37% were performed in Croatia (351:202). In the following four-year period (2008-2011) there was a significant increase in the number of surgeries performed in Croatia when compared to those performed abroad (59:4% or 380:264). Independent EACTS analysis points to a positive trend of gradual increase in the number of surgeries and acceptance of higher complexity level of surgeries performed in Croatia, while maintaining the assigned margin (early mortality below 5%). Contribution: Proper selection of patients according to the complexity of cardiac surgical procedure is a prerequisite for both low mortality and fewer postsurgical complications. Professional advance relying on close cooperation with foreign centers is much faster and more acceptable than by "learning curves". CONCLUSION: Pediatric cardiac surgery in the developing countries must rely on the experiences of developed cardiac surgical centers in the neighboring countries due to complexity of congenital heart defects. Pediatric cardiology is inherently a public health problem, but the problem exacerbates with the appearance of a large number of adults with congenital heart defects (GUCH patients).

[Clinical and epidemiological features of the mitral valve prolaps in children]. / Klinicka i epidemioloska obiljezja prolapsa mitralne valvule u djece.

The study deals with the incidence and clinical significance of mitral valve prolapse in the population of outpatient pediatric cardiology patients in the time period from November 1999 to April 2004. The sample included 1187 children of both sexes, 688 of whom had a structural cardiac anomaly (57.9%), and the prolapse was diagnosed in 51 children (4.3%), largely female (f:m = 7.5:1). The average age at establishing diagnosis was 12.4 +/- 2.9 years (range 6-19 years). The children were followed 3.1 +/- 0.9 years (1-4 years of age). In 25 children (49%) associated mitral valve insufficiency was found, mostly of the 1st degree (80%). During follow up, neither the progression of the insufficiency nor any other complication was observed (arrhytmia, tromboembolism) in any of the children. Dolichostenomely was found in 10 children (19.6%), and both the development of insufficiency (p = 0.464, df = 2, chi2 = 1.54) and the difference in constitution (p = 0.766, df = 4, chi2 = 1.83) were irrelevant of sex. Typical subjective symptoms were observed in 37 children (72.5%), 22 of whom were treated with beta-blockers (propranolol) (43.1%). The average age of the patients treated with 3-blockers (13.7 +/- 2.5 yr) was statistically different from the average age of untreated patients (11.5 +/- 2.9 yr), hence the probability of the influence of neurohormonal factors on the development of subjective symptoms in advanced puberty (p = 0.006, t = -2.86). The most common clinical symptom is chest-pain (95% of the group with stronger symptoms). When treated, the symptoms disappear in 82% of the patients. Mitral valve prolapse is the entity of favourable clinical course. The prophylaxis of infective endocarditis should be performed in the group with mitral insufficiency, and the children with stronger symptoms should be treated with beta-blockers.