Successful treatment of fetal hemolytic disease due to glucose phosphate isomerase deficiency (GPI) using repeated intrauterine transfusions : a case report

Hemolytic anemia due to GPI deficiency can be severe and life threatening during fetal life. When parents decline invasive testing, ultrasound monitoring of fetuses at risk is feasible. Intrauterine transfusion can be effective for the treatment of severe fetal anemia due to GPI deficiency

Impact of Fibroscan® on management of chronic viral hepatitis in clinical practice

Background. Liver stiffness measurement (LSM) using Fibroscan® is an increasingly popular non-invasive me¬thod for quantifying liver fibrosis in patients with chronic viral hepatitis. We aimed to explore potential im¬pact of Fibroscan® on clinical management.Material and methods. 133 patients with chronic hepatitis B (HBV, n = 75) or C (HCV, n = 58) underwent Fibroscan® measurement. LSM results were compared with li-ver biopsy results, ultrasound, and APRI-scores, and the impact of LSM on clinical management was evalua¬ted.Results. LSM results indicated fibrosis stage F0-F1 in 84 patients (63%), F2 in 28 (21%), F3 in 8 (6%), and F4 in 13 patients (10%). Nineteen patients had liver biopsies within one year of LSM. In ten patients, LSM and biopsy showed the same fibrosis stage, in 8 there was one stage difference, and in 1 three stages di¬fference. Ultrasound only showed cirrhosis in three patients, who all exhibited advanced cirrhosis at LSM. There was a statistically significant, but weak correlation between LSM results and APRI scores (r = 0.31, p-value < 0.001). LSM results changed clinical management in 39% of patients (55 cases): in 15 patients antivi¬ral treatment was indicated, in 21 patients surveillance for hepatocellular carcinoma was indicated, and 19 successfully treated hepatitis C patients could be discharged from clinical follow-up in absence of severe fibrosis or cirrhosis.Conclusion. LSM appears to be a valuable non-invasive tool to manage patients with chronic viral hepatitis in clinical practice

History of non-fatal cardiovascular disease in a cohort of Dutch and British patients with haemophilia

Objective Cardiovascular disease (CVD) mortality is reported to be lower in haemophilia patients than in the general population, but information on the occurrence of non-fatal CVD is lacking. The aim of our study was to assess CVD history in a cohort of living haemophilia patients. Methods Retrospective data on the occurrence of myocardial infarction, angina pectoris, ischaemic stroke and intracranial bleeding in 709 living Dutch and British haemophilia patients aged 30 similar to yr or older were analysed and compared with the general age-matched male population. Results There was a trend towards a lower cumulative incidence of myocardial infarction (1.7% vs. 4.0%) and ischaemic stroke (0% vs. 1.5%) in patients with severe haemophilia than in the general population, while the occurrence of angina pectoris was similar (3.2 vs. 3.7%). As expected, the cumulative incidence of intracranial bleeding was, on the other hand, significantly increased in haemophilia patients (1.6% vs. 0.4% in the general population). Conclusion Our results suggest a protective effect of severe haemophilia against acute ischaemic CVD

Managing women‐specific bleeding in inherited bleeding disorders: A multidisciplinary approach

Introduction: Multidisciplinary management of women-specific bleeding is important to preserve quality of life, healthy reproduction and social participation of women and girls with bleeding disorders (WBD). Aim: To support appropriate multidisciplinary care for WBD in haemophilia treatment centres. Methods: Two case examples are presented and management issues discussed from different health care perspectives, including the nurse, patient, psychologist, gynaecologist, geneticist, psychosexual therapist and haematologist. Results: Woman with bleeding disorders may experience heavy menstruation from menarche onwards. This has a physical and psychosocial impact requiring a multidisciplinary approach. If a woman with an inherited bleeding disorder desires to become pregnant, preconception counselling is essential, to discuss genetic diagnosis, state of the art treatment options for the bleeding disorder in question and possible choices to prevent having an affected child, as well as maternal bleeding risks during conception, delivery and the post-partum period. Conclusion: Adequate management and good education of WBD requires a patient-centred multidisciplinary approach with experienced specialists in a haemophilia treatment centre

Increased prevalence of hypertension in haemophilia patients

An increased prevalence of hypertension is reported in haemophilia patients, but data from large, unbiased studies are lacking. The aim of our study was to cross-sectionally assess the prevalence of hypertension in a large cohort of 701 haemophilia patients. Blood pressure (BP) measurements performed in 386 Dutch and 315 UK haemophilia patients aged 30 years or older were analysed and compared with the general age-matched male population. Mean values of up to three BP measurements were used when available. Hypertension was defined as BP over 140/90 mmHg and/or the use of antihypertensive medication. A total of 49% of patients had severe haemophilia. Mean age was 49.8 years. The prevalence of hypertension was significantly higher in haemophilia patients (49%, 95% confidence interval [CI] 45-53) than in the general population (40%, 95% CI 37-43). The prevalence of hypertension was higher in patients with severe haemophilia than in those with non-severe disease, but similar across haemophilia types and in Dutch and UK patients. Multiple BP measurements were available for 70%. The prevalence of hypertension was similar in patients with multiple BP measurements and the complete cohort. Hypertension was not significantly associated with renal function, a history of renal bleeding or with infection with hepatitis C or HIV, but it was associated with overweight/obesity and age. In conclusion, the prevalence of hypertension is higher in haemophilia patients than in the general population. The cause of this increased prevalence is unknown. Blood pressure measurements should be part of standard care in haemophilia patients aged 30 years or older

Managing women-specific bleeding in inherited bleeding disorders: A multidisciplinary approach

Introduction: Multidisciplinary management of women-specific bleeding is important to preserve quality of life, healthy reproduction and social participation of women and girls with bleeding disorders (WBD). Aim: To support appropriate multidisciplinary care for WBD in haemophilia treatment centres. Methods: Two case examples are presented and management issues discussed from different health care perspectives, including the nurse, patient, psychologist, gynaecologist, geneticist, psychosexual therapist and haematologist. Results: Woman with bleeding disorders may experience heavy menstruation from menarche onwards. This has a physical and psychosocial impact requiring a multidisciplinary approach. If a woman with an inherited bleeding disorder desires to become pregnant, preconception counselling is essential, to discuss genetic diagnosis, state of the art treatment options for the bleeding disorder in question and possible choices to prevent having an affected child, as well as maternal bleeding risks during conception, delivery and the post-partum period. Conclusion: Adequate management and good education of WBD requires a patient-centred multidisciplinary approach with experienced specialists in a haemophilia treatment centre

Unfavourable cardiovascular disease risk profiles in a cohort of Dutch and British haemophilia patients

<p>Cardiovascular disease (CVD) mortality is reported to be decreased in haemophilia patients, but reports on the prevalence of CVD risk factors are conflicting. A cross-sectional assessment of CVD risk profiles was performed in a large cohort of haemophilia patients. Baseline data on CVD risk factors of 709 Dutch and UK haemophilia patients aged >= 30 years were analysed and compared with the general age-matched male population. CVD risk profiles were assessed using the QRISK (R) 2-2011 and SCORE algorithms. Although QRISK (R) 2 was only validated in the UK, comparison with SCORE indicated similar properties of QRISK (R) 2 in both Dutch and UK patients (correlation 0.86). Mean age was 49.8 years. Hypertension was more common in haemophilia patients than in the general population (49% vs. 40%), while the prevalences of obesity and hypercholesterolaemia were lower (15 vs. 20% and 44 vs. 68%, respectively), and those of diabetes and smoking were similar. The predicted 10-year QRISK (R) 2 risk was significantly higher in haemophilia patients than in the general population (8.9 vs. 6.7%), indicating more unfavourable cardiovascular disease risk profiles. This increased risk became apparent after the age of 40 years. Our results indicate an increased prevalence of hypertension and overall more unfavourable CVD risk profiles in haemophilia patients compared with the general age-matched male population.</p>

DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands

Joubert syndrome (JBS) is a clinically variable and genetically heterogeneous developmental brain disorder with autosomal recessive inheritance. Five genes, AHI1, NPHP1, CEP290, MKS3, and RPGRIP1L, and two additional loci on chromosome 9 and 11 have been identified so far. The relative contributions of AHI1 mutations and NPHP1 deletions have not yet been determined in a population-based JBS patient cohort. We therefore undertook a nationwide survey of JBS in the Netherlands and performed DNA analysis of the AHI1 and NPHP1 genes, as well as a new candidate gene CYCLIN D1. We obtained clinical data and DNA samples of 25 Dutch JBS patients. DNA analysis of AHI1 revealed pathogenic homozygous or compound heterozygous AHI1 mutations in four patients (16%). Based on the birth prevalence of about 1 in 100,000 for JBS in the Netherlands, we estimated a carrier frequency of AHI1 mutations of approximately 1 in 400. In another two patients, the AHI1 mutation Arg830Trp was identified (homozygously and heterozygously), a possible low penetrance allele. No deletions of NPHP1 or CYCLIN D1 mutations were detected in these 25 patients. In the four patients with AHI1 mutations, retinal disease (Leber congenital amaurosis or retinal dystrophy) was present in two, whereas none had renal disease. Pooling our data and data from the literature, retinal disease seems to occur in 75% of AHI1-associated JBS patients. Renal disease is present in 10% at most. We conclude that AHI1 mutations are an important cause of JBS in Dutch patients, and should always be looked for in patients suspected of JBS, especially when retinal dystrophy is present. Patients with AHI1 mutations should be regularly checked for retinal and renal disease up until adolescenc

Putting genome-wide sequencing in neonates into perspective

Purpose: Several studies have reported diagnostic yields up to 57% for rapid exome or genome sequencing (rES/GS) as a single test in neonatal intensive care unit (NICU) patients, but the additional yield of rES/GS compared with other available diagnostic options still remains unquantified in this population. Methods: We retrospectively evaluated all genetic NICU consultations in a 2-year period. Results: In 132 retrospectively evaluated NICU consultations 27 of 32 diagnoses (84.4%) were made using standard genetic workup. Most diagnoses (65.6%) were made within 16 days. Diagnostic ES yield was 5/29 (17.2%). Genetic diagnoses had a direct effect on clinical management in 90.6% (29/32) of patients. Conclusions: Our study shows that exome sequencing has a place in NICU diagnostics, but given the associated costs and the high yield of alternative diagnostic strategies, we recommend to first perform clinical genetic consultation

Correction: Putting genome-wide sequencing in neonates into perspective

The original version of this Article contained an error in the spelling of the author Pleuntje J. van der Sluijs, which was incorrectly given as Eline (P. J.) van der Sluijs. This has now been corrected in both the PDF and HTML versions of the Article