Novel compound heterozygous mutations in AMN cause Imerslund-Gräsbeck syndrome in two half-sisters: a case report.

BACKGROUND: Imerslund-Gräsbeck Syndrome (IGS) is a rare autosomal recessive disease characterized by intestinal vitamin B12 malabsorption. Clinical features include megaloblastic anemia, recurrent infections, failure to thrive, and proteinuria. Recessive mutations in cubilin (CUBN) and in amnionless (AMN) have been shown to cause IGS. To date, there are only about 300 cases described worldwide with only 37 different mutations found in CUBN and 30 different in the AMN gene. CASE PRESENTATION: We collected pedigree structure, clinical data, and DNA samples from 2 Caucasian English half-sisters with IGS. Molecular diagnostics was performed by direct Sanger sequencing of all 62 exons of the CUBN gene and 12 exons of the AMN gene. Because of lack of parental DNA, cloning, and sequencing of multiple plasmid clones was performed to assess the allele of identified mutations. Genetic characterization revealed 2 novel compound heterozygous AMN mutations in both half-sisters with IGS. Trans-configuration of the mutations was confirmed. CONCLUSION: We have identified novel compound heterozygous mutations in AMN in a family from the United Kingdom with clinical features of Imerslund-Gräsbeck Syndrome.

Prognostic value of cardiac tests in potential kidney transplant recipients: a systematic review.

BACKGROUND: Whether abnormal myocardial perfusion scintigraphy (MPS), dobutamine stress echocardiography (DSE) or coronary angiography, performed during preoperative evaluation for potential kidney transplant recipients, predicts future cardiovascular morbidity is unclear. We assessed test performance for predicting all-cause mortality, cardiovascular mortality and major adverse cardiac events (MACE). METHODS: We searched MEDLINE and EMBASE (to February 2014), appraised studies, and calculated risk differences and relative risk ratios (RRR) with 95% confidence intervals (95% CI) using random effects meta-analysis. RESULTS: Fifty-two studies (7401 participants) contributed data to the meta-analysis. Among the different tests, similar numbers of patients experienced MACE after an abnormal test result compared with a normal result (risk difference: MPS 20 per 100 patients tested [95% CI, 0.11-0.29], DSE 24 [95% CI, 0.10-0.38], and coronary angiography 20 [95% CI, 0.08-0.32; P = 0.91]). Although there was some evidence that coronary angiography was better at predicting all-cause mortality than MPS (RRR, 0.69; 95% CI, 0.49-0.96; P = 0.03) and DSE (RRR, 0.72; 95% CI, 0.50-1.02; P = 0.06), noninvasive tests were as good as coronary angiography at predicting cardiovascular mortality (RRR, MPS, 0.89; 95% CI, 0.38-2.10; P = 0.78; DSE, 1.09; 95% CI, 0.12-10.05; P = 0.93), and MACE (RRR: MPS, 1.09; 95% CI, 0.64-1.86; P = 0.74; DSE, 1.56; 95% CI, 0.71-3.45; P = 0.25). CONCLUSIONS: Noninvasive tests are as good as coronary angiography at predicting future adverse cardiovascular events in advanced chronic kidney disease. However, a substantial number of people with negative test results go on to experience adverse cardiac events.

Anti-neutrophil cytoplasmic antibody (ANCA) associated small-vessel vasculitis in a patient with diabetic nephropathy and autoimmune polyendocrinopathy syndrome (APS) Type 2: a case report.

We present a 42-year-old woman with pre-existing autoimmune polyendocrinopathy syndrome (APS) Type 2 and chronic kidney disease due to Type 1 diabetic nephropathy, who developed a rapid deterioration in renal function due to perinuclear anti-neutrophil cytoplasmic antibody (pANCA)-associated vasculitis. Although possibly a chance occurrence, ANCA have been detected more frequently in patients with a history of certain autoimmune diseases. Such an association may simply reflect an underlying tendency to immune system dysfunction in these patients and the finding of positive ANCA serology does not reliably herald the development of ANCA-associated vasculitis. However, our case illustrates that positive ANCA serology in such circumstances is not always a benign phenomenon and should still be interpreted within the clinical context. Moreover, clinicians managing patients with pre-existing autoimmune disease should maintain a low threshold for appropriate assessment should such patients develop evidence suggestive of vasculitis.

Cardiac testing for coronary artery disease in potential kidney transplant recipients: a systematic review of test accuracy studies.

BACKGROUND: Cardiovascular disease is the leading cause of death after kidney transplant. Screening for coronary artery disease is integral to pretransplant evaluation, although the relative performance of different tests is uncertain. STUDY DESIGN: Systematic review of diagnostic test accuracy studies using hierarchical summary receiver operating characteristic analysis. SETTING & POPULATION: Kidney transplant candidates undergoing pretransplant assessment. SELECTION CRITERIA OF STUDIES: Studies evaluating the accuracy of screening tests for detecting coronary artery disease. INDEX TESTS: Any non- or minimally invasive test used to diagnose coronary artery disease. REFERENCE TEST: Coronary angiography. RESULTS: 11 studies (690 participants) evaluated dobutamine stress echocardiography; 7 (317 participants), myocardial perfusion scintigraphy; 2 (129 participants), exercise stress electrocardiography; and 2 (121 participants), other tests. Dobutamine stress echocardiography had pooled sensitivity of 0.80 (95% CI, 0.64-0.90) and specificity of 0.89 (95% CI, 0.79-0.94). Myocardial perfusion scintigraphy had pooled sensitivity of 0.69 (95% CI, 0.48-0.85) and specificity of 0.77 (95% CI, 0.59-0.89). Head-to-head comparison of dobutamine stress echocardiography and myocardial perfusion scintigraphy (2 studies; 116 participants) showed that dobutamine stress echocardiography had higher specificity and at least equivalent or higher sensitivity. Indirect comparison suggested dobutamine stress echocardiography may have improved accuracy over myocardial perfusion scintigraphy (P = 0.07). LIMITATIONS: Power to detect differences in accuracy between tests is limited due to sparse data. Absence of significant coronary artery disease may not necessarily correlate with cardiac event-free survival after transplant. CONCLUSIONS: Dobutamine stress echocardiography may perform better than myocardial perfusion scintigraphy; however, additional studies directly comparing dobutamine stress echocardiography and myocardial perfusion scintigraphy are needed. Further research should focus on assessing the ability of functional tests to predict postoperative outcome.