The impact of consanguinity on the frequency of inborn errors of metabolism

Inborn errors of metabolism (IEM) are a heterogeneous group of genetic disorders present in all ethnic groups. We investigated the frequency of consanguinity among parents of newborns with IEM diagnosed by neonatal screening.Data were obtained from 15years of expanded newborn screening for selected IEM with autosomal recessive mode of inheritance, a national screening program of newborns covering the period from 2002 until April 2017. Among the 838,675 newborns from Denmark, the Faroe Islands and Greenland, a total of 196 newborns had an IEM of whom 155 from Denmark were included in this study. These results were crosschecked against medical records. Information on consanguinity was extracted from medical records and telephone contact with the families.Among ethnic Danes, two cases of consanguinity were identified in 93 families (2.15%). Among ethnic minorities there were 20 cases of consanguinity among 33 families (60.6%). Consequently, consanguinity was 28.2 times more frequent among descendants of other geographic place of origin than Denmark. The frequency of consanguinity was conspicuously high among children of Pakistani, Afghan, Turkish and Arab origin (71.4%). The overall frequency of IEM was 25.5 times higher among children of Pakistani, Turkish, Afghan and Arab origin compared to ethnic Danish children (5.35:10,000 v 0.21:10,000). The frequency of IEM was 30-fold and 50-fold higher among Pakistanis (6.5:10,000) and Afghans (10.6:10,000), respectively, compared to ethnic Danish children.The data indicate a strong association between consanguinity and IEM. These figures could be useful to health professionals providing antenatal, pediatric, and clinical genetic services. Keywords: Inherited metabolic disease, Consanguinity, Ethnic group, Neonatal screenin

Gender-partitioned patient medians of serum albumin requested by general practitioners for the assessment of analytical stability

AbstractBackground:Recently, the use of separate gender-partitioned patient medians of serum sodium has revealed potential for monitoring analytical stability within the optimum analytical performance specifications for laboratory medicine. The serum albumin concentration depends on whether a patient is sitting or recumbent during phlebotomy. We therefore investigated only examinations requested by general practitioners (GPs) to provide data from sitting patients.Methods:Weekly and monthly patient medians of serum albumin requested by GP for both male and female patients were calculated from the raw data obtained from three analysers in the hospital laboratory on examination of samples from those &gt;18 years. The half-range of medians were applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated (females/males).Results:The medians for male and female patients were closely related despite considerable variation due to the current analytical variation. This relationship was confirmed by the calculated half-range for the monthly ratio between the genders of 0.44%, which surpasses the optimum analytical performance specification for bias of serum albumin (0.72%). The weekly ratio had a half-range of 1.83%, which surpasses the minimum analytical performance specifications of 2.15%.Conclusions:Monthly gender-partitioned patient medians of serum albumin are useful for monitoring of long-term analytical stability, where the gender medians are two independent estimates of changes in (delta) bias: only results requested by GP are of value in this application to ensure that all patients are sitting during phlebotomy.</jats:sec

Separate patient serum sodium medians from males and females provide independent information on analytical bias

AbstractBackground:During monitoring of monthly medians of results from patients undertaken to assess analytical stability in routine laboratory performance, the medians for serum sodium for male and female patients were found to be significantly related.Methods:Daily, weekly and monthly patient medians of serum sodium for both male and female patients were calculated from results obtained on samples from the population &gt;18 years on three analysers in the hospital laboratory. The half-range of medians was applied as an estimate of the maximum bias. Further, the ratios between the two medians were calculated.Results:The medians of both genders demonstrated dispersions over time, but they were closely connected in like patterns, which were confirmed by the half-range of the ratios of medians for males and females that varied from 0.36% for daily, 0.14% for weekly and 0.036% for monthly ratios over all instruments.Conclusions:The tight relationship between the gender medians for serum sodium is only possible when raw laboratory data are used for calculation. The two patient medians can be used to confirm both and are useful as independent estimates of analytical bias during constant calibration periods. In contrast to the gender combined median, the estimate of analytical bias can be confirmed further by calculation of the ratios of medians for males and females.</jats:sec