Newborn screening for methylmalonic acidurias--optimization by statistical parameter combination.

With the introduction of tandem mass spectrometry, newborn screening for disorders of propionate metabolism became widely available. However, there is controversy whether population screening for these disorders should be performed. The most widely used primary metabolite C(3) itself has a poor specificity or lacks 100% sensitivity for milder forms and/or defects of cobalamin metabolism. Strategies to improve specificity have included the calculation of metabolite ratios (e.g. C(3)/C(2)) or second-tier strategies with analysis of methylmalonic acid or 2-methylcitric acid from the primary screening specimen. We report the results of a new statistical approach to identify parameter combinations that allow for 100% sensitivity as well as increased specificity. The promising results of this alternative approach will have to be substantiated on larger data sets.

Implementation of extended neonatal screening and a metabolic unit in the State of Qatar: developing and optimizing strategies in cooperation with the Neonatal Screening Center in Heidelberg.

Qatar is a country in the Gulf area and member of the Gulf Cooperation Council states. The country is populated by original Qatari tribes that amount to about 200,000 people and about 600,000 expatriates mainly from Arabic and Asian countries. Inbreeding over centuries and high rates of consanguinity in the Qatari population and in some groups of expatriates, in addition to large family sizes and rapid population growth, have contributed to a high frequency of autosomal recessive disorders. In December 2003 Hamad Medical Corporation in Doha and the University Children's Hospital of Heidelberg, Germany, started an extended state-wide neonatal screening programme for metabolic and endocrine disorders, with the laboratory situated in Heidelberg, Germany. All aspects of the screening process had to be adapted to the unique situation of the laboratory being 6000 km from the birthplace of the neonates. Within 32 months, samples of 25,214 neonates were screened. In 28 cases an endocrine or metabolic diagnosis was identified (incidence 1:901, in Germany 1:1728). In particular, a variety of monogenic metabolic diseases were prevalent, with 19 patients detected giving an incidence of metabolic diseases of 1:1327 (Germany 1:2517). Each euro spent on the screening programme saved more than 25 euros in health and social costs. The programme revealed a high incidence of treatable inborn metabolic diseases in the population of Qatar. A reliable screening for classical homocystinuria showing a unique incidence of >1:3000 and for sickle cell disease has now been added.