Minder E.I.,Zentrallabor |
Schneider-Yin X.,Zentrallabor |
Mamet R.,Beilinson Hospital |
Horev L.,Hebrew University of Jerusalem |
And 7 more authors.
Journal of the European Academy of Dermatology and Venereology | Year: 2010
Background Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by the deficiency of ferrochelatase (FECH) in the haem biosynthetic pathway. In the majority of families, EPP is transmitted as a pseudodominant trait. Autosomal recessive form of EPP is found in only about 3% of the families. Objectives In this study, we describe a 6-year-old boy who suffered from both EPP and palmar keratoderma. Methods and Results A novel homoallelic missense mutation (p.Ser318Tyr) was identified in the FECH gene. In addition, a region of homozygosity of approximately 6.8 Mb was observed in chromosome 18 of the patient by both microsatellite and SNP array. The parents of the patient, both of Palestinian (Jordanian) origin, were heterozygous for the S318Y mutation, although no history of consanguinity was known. Microsatellite genotyping identified a partial haplotype from each parent that corresponds to the region of homozygosity in the patient. Assuming S318Y is a founder mutation, the number of generations separating the two parents from their common ancestor from whom they inherited S318Y was estimated as 21.7 (95% CI 3.42-69.7). Conclusion EPP was therefore inherited as an autosomal recessive trait in the family. This study confirms the association between palmar keratoderma and autosomal recessive EPP. © 2010 The Authors.
Risch L.,Labormedizinische zentren Dr. Risch |
Risch L.,University of Liechtenstein |
Risch L.,Innsbruck Medical University |
Lhotta K.,Academic Teaching Hospital |
And 4 more authors.
Clinical Chemistry and Laboratory Medicine | Year: 2014
Background: In chronic kidney diseases of various etiologies, the urinary excretion of uromodulin is usually decreased in parallel with the glomerular filtration rate. This study aimed to investigate whether serum uromodulin is associated with kidney function. Methods: Within the framework of the Seniorlabor study, a subset of subjectively healthy individuals 60 years of age and older were included in the study. Serum uromodulin was measured with ELISA. The relationship between serum uromodulin and different stages of kidney function (i.e., cystatin C-based 2012-CKD-EPI eGFRCysC>90 mL/min/1.73 m2, 60-89 mL/min/1.73 m2, 45-59 mL/min/1.73 m2, and <45 mL/min/1.73 m2) was investigated. Furthermore, the relationship between serum uromodulin and other markers of kidney function (i.e., creatinine, cystatin C, and urea) was assessed. Results: In total, 289 participants (140 males/149 females; mean age 71±7 years) were included in the study. There were significant differences in serum uromodulin among the four groups according to different kidney function stages (p<0.001). Serum uromodulin displayed inverse relationships with creatinine (r=-0.39), cystatin C (r=-0.42), and urea (r=-0.30) and, correspondingly, a positive relationship with eGFRCysC (r=0.38, p<0.001 for all). These associations remained intact when fitting a regression model that incorporated age, gender, body mass index, and current smoking status as covariates. Conclusions: Serum uromodulin behaves in a manner opposite that of the different conventional renal retention markers by displaying lower concentrations with decreasing kidney function. As uromodulin is produced by the cells of the thick ascending limb of the loop of Henle, lower uromodulin serum levels may reflect a reduction in number or function of these cells in chronic kidney disease. © by De Gruyter 2014.
Stanga Z.,University of Bern |
Nock S.,University of Liechtenstein |
Medina-Escobar P.,Labormedizinische zentren Dr. Risch |
Nydegger U.E.,Labormedizinische zentren Dr. Risch |
And 3 more authors.
PLoS ONE | Year: 2013
Background:β2-microglobulin has been increasingly investigated as a diagnostic marker of kidney function and a prognostic marker of adverse outcomes. To date, non-renal determinants of β2-microglobulin levels have not been well described. Non-renal determinants are important for the interpretation and appraisal of the diagnostic and prognostic value of any endogenous kidney function marker.Methods:This cross-sectional analysis was performed within the framework of the www.seniorlabor.ch study, which includes subjectively healthy individuals aged ≥60 years. Factors known or suspected to have a non-renal association with kidney function markers were investigated for a non-renal association with serum β2-microglobulin. As a marker of kidney function, the Berlin Initiative Study equation 2 for the estimation of the estimated glomerular filtration rate (eGFRBIS2) in the elderly was employed.Results:A total of 1302 participants (714 females and 588 males) were enrolled in the study. The use of a multivariate regression model adjusting for age, gender and kidney function (eGFRBIS2) revealed age, male gender, and C-reactive protein level to be positively associated with β2-microglobulin levels. In addition, there was an inverse non-renal relationship between systolic blood pressure, total cholesterol and current smoking status. No association with markers of diabetes mellitus, body stature, nutritional risk, thyroid function or calcium and phosphate levels was observed.Conclusions:Serum β2-microglobulin levels in elderly subjects are related to several non-renal factors. These non-renal factors are not congruent to those known from other markers (i.e. cystatin C and creatinine) and remind of classical cardiovascular risk factors. © 2013 Stanga et al.
Rohrbach J.M.,University of Tübingen |
Harbeck M.,Bayerische Staatssammlung fur Anthropologie und Palaoanatomie |
Holzhauser P.,Fachburo fur Angewandte Geologie |
Tekeva-Rohrbach C.I.,University of Tübingen |
And 2 more authors.
Klinische Monatsblatter fur Augenheilkunde | Year: 2012
During an excavation in Regensburg/Germany the skeleton of an approximately 20-year-old Roman man was found who was buried in the 3rd/4th century after Christ. A "stoneo" was found which fitted into the left orbit precisely. After a thorough investigation of the "stoneo" and with the ophthalmohistorical literature in mind an orbital "implanto" as well as a petrified medical paste ("Kollyriumo") could be ruled out almost with certainty. Possibly the "stoneo" served another medical purpose or was used for protection of the eye. © Georg Thieme Verlag KG Stuttgart · New York.
Risch M.,Zentrallabor |
Meier D.W.,Labormedizinisches Zentrum Dr. Risch |
Sakem B.,Labormedizinisches Zentrum Dr. Risch |
Medina Escobar P.,Labormedizinisches Zentrum Dr. Risch |
And 3 more authors.
BMC Geriatrics | Year: 2015
Background: The vitamin B12 and folate status in nonanaemic healthy older persons needs attention the more so as decrease in levels may be anticipated from reduced haematinic provision and/or impaired intestinal uptake. Methods: A total of 1143 subjectively healthy Swiss midlands participants (637 females and 506 males), ≥60 years of age were included in this study. Levels of vitamin B12, holotranscobalamin (holoTC), methylmalonic acid (MMA), homocysteine (Hcy), serum folate, red blood cell (RBC) folate were measured. Further, Fedosov's wellness score was determined. Associations of age, gender, and cystatin C/creatinine-based estimated kidney function, with the investigated parameters were assessed. Reference intervals were calculated. Further, ROC analysis was done to assess accuracy of the individual parameters in recognizing a deficient vitamin B12 status. Finally, decision limits for sensitive, specific and optimal recognition of vitamin B12 status with individual parameters were derived. Results: Three age groups: 60-69, 70-79 and ≥ 80 had median B12 (pmol/L) levels of 237, 228 and 231 respectively (p = 0.22), holoTC (pmol/L) of 52, 546 and 52 (p = 0.60) but Hcy (μmol/L) 12, 15 and 16 (p < 0.001), MMA (nmol/L) 207, 221 and 244 (p < 0.001). Hcy and MMA (both p < 0.001), but not holoTC (p = 0.12) and vitamin B12 (p = 0.44) were found to be affected by kidney function. In a linear regression model Fedosov's wellness score was independently associated with kidney function (p < 0.001) but not with age. Total serum folate and red blood cell (RBC) folate drift apart with increasing age: whereas the former decreases (p = 0.01) RBC folate remains in the same bandwidth across all age groups (p = 0.12) A common reference interval combining age and gender strata can be obtained for vitamin B12 and holoTC, whereas a more differentiated approach seems warranted for serum folate and RBC folate. Conclusion: Whereas the vitamin B12 and holoTC levels remain steady after 60 years of age, we observed a significant increment in MMA levels accompanied by increments in Hcy; this is better explained by age-related reduced kidney function than by vitamin B12 insufficiency. Total serum folate levels but not RBC folate levels decreased with progressing age. © 2015 Risch et al.
Bishop D.F.,Mount Sinai School of Medicine |
Xiaoye S.-Y.,Zentrallabor |
Clavero S.,Mount Sinai School of Medicine |
Yoo H.-W.,University of Ulsan |
And 2 more authors.
Blood | Year: 2010
Splicing mutations account for approximately 10% of lesions causing genetic diseases, but few branchpoint sequence (BPS) lesions have been reported. In 3 families with autosomal recessive congenital erythropoietic porphyria (CEP) resulting from uroporphyrinogen III synthase (URO-synthase) deficiency, sequencing the promoter, all 10 exons and the intron/exon boundaries did not detect a mutation. Northern analyses of lymphoblast mRNAs from 2 patients and reverse-transcribed polymerase chain reaction (RT-PCR) of lymphoblast mRNAs from all 3 patients revealed multiple longer transcripts involving intron 9 and low levels of wild-type message. Sequencing intron 9 RT-PCR products and genomic DNA in each case revealed homozygosity for a novel BPS mutation (c.661-31T→G) and alternatively spliced transcripts containing 81, 246, 358, and 523 nucleotides from intron 9. RT-PCR revealed aberrant transcripts in both wild-type and CEP lymphoblasts, whereas BPS mutation reduced the wild-type transcript and enzyme activity in CEP lymphoblasts to approximately 10% and 15% of normal, respectively. Although the +81-nucleotide alternative transcript was in-frame, it only contributed approximately 0.2% of the lymphoblast URO-synthase activity. Thus, the BPS mutation markedly reduced the wildtype transcript and enzyme activity, thereby causing the disease. This is the first BPS mutation in the last intron, presumably accounting for the observed 100% intron retention without exon skipping. © 2010 by The American Society of Hematology.
Endler G.,Medical University of Vienna |
Slavka G.,Zentrallabor |
Perkmann T.,Medical University of Vienna |
Haushofer A.,Institute For Laboratoriumsmedizin
Hamostaseologie | Year: 2010
Due to their complex preanalytics coagulation tests show a higher rate of rejected samples due to insufficient quality and a higher intra- and inter-individual test variability. In the last years several guidelines addressed this issue in an effort to standardize preanalytic procedures. However, in daily laboratory work, these guidelines frequently cannot be fully executed, due to technical limitations or sample transport logistics. In this manuscript several important issues in sample collection, handling and transportation will be discussed. Since the stability and variability of routine coagulation tests such as prothrombin time and partial prothrombin time are significantly influenced by a number of variables such as tube type, manufacturer, reagents used and analyzer systems, it is recommended that each laboratory develops its own manuals for sample collection, based on published data and internal evaluations. © Schattauer 2010.
Therapeutische Umschau | Year: 2015
More than half of the so called “laboratory errors” has already happened before the analysis starts in the laboratory and many mistakes are made after the analysis itself. Pre- and post-analytical errors cause 60 to 90% of all unexpected or erroneous values; only 10 to 15% are caused by analytical problems. Internal quality control and external quality assessments are a matter of course today while standardisation still could be improved. The pre- and post-analytical processes however are only scarcely supervised. Good patient preparation, reliable patient identification and correct blood draws still cannot be taken for granted – improved training and education are necessary. There is also room for improvement in the communication of the results and the implementation of the consequences thereof. Errors in all phases of the analytical process contain valuable clues for optimisations. An improved culture of failure management would allow tapping the full potential of these clues. © 2015 Verlag Hans Huber.
PubMed | Zentrallabor
Type: Journal Article | Journal: Wiener medizinische Wochenschrift (1946) | Year: 2012
Autoimmune diseases are a clinically heterogeneous group of disorders that represent a challenge for the general practitioner in daily routine. Except for rheumatoid arthritis, which is one of the most frequent autoimmune diseases with a prevalence of approximately 1 % of the population, systemic autoimmune disorders are rare. Thus outside specialized wards it might be a challenge to diagnose the underlying autoimmune disease considering the often kaleidoscopic clinical manifestations. Together with careful anamnesis and suspicious clinical symptoms determination of specific autoantibodies can support the suspected diagnosis. The Austrian group of the European autoimmune standardization initiative (EASI) firstly published this guide 2009 with the aim to provide a map through the jungle of the biomarkers for autoimmune diseases for the general practitioner.
PubMed | Zentrallabor
Type: | Journal: Journal of inherited metabolic disease | Year: 2011
Erythropoietic protoporphyria (EPP) is a rare hereditary disorder due to a partial deficiency of ferrochelatase (FECH). The genotype of EPP patients features a mutation on one allele of the FECH gene and a common hypomorphic FECH IVS3-48c on the other allele (M/c). The resulting enzyme activity in patients is 35% of that in normal individuals. Ferrochelatase deficiency results in the accumulation of protoporphyrin in the skin, which is responsible for the clinical symptom of cutaneous photosensitivity in patients. In this study, we report the identification of a novel FECH mutation delT23 in an 11-member EPP family of Jewish origin. Two EPP siblings shared an identical genotype of delT23/IVS3-48c (M/c). They were both photosensitive and showed highly increased erythrocyte protoporphyrin. The genotype of the patients mother, who did not present with any EPP clinical symptoms, was delT23/IVS3-48t (M/t). The patients father, an offspring of consanguineous parents, was homozygous IVS3-48 c/c. He exhibited a mild photosensitivity, and an increase of 4-fold in erythrocyte protoporphyrin. His FECH mRNA amount was 71% of that of genotype t/t. It is the first reported case of an individual with c/c genotype who exhibits both biochemical and clinical indications of EPP. These results suggest that IVS3-48c is a functional variant of ferrochelatase. The clinical symptoms and biochemical abnormalities in the patients father could be the result of an interaction between genetic and environmental factors. In addition, the frequency of IVS3-48c in the Ashkenazi Jewish population was estimated at 8%, which is similar to that in the European populations.