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

Abstract

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.

Expanded Newborn Screening Programme in Saudi Arabia: Are We Ready?

“…3,4 The incidence reported in previous pilot studies in Saudi Arabia for the period 1995-1998 was 1:1381, 1 and for the year 2000, the incidence was 1:690 (personal experience). 2 It is important to implement a good legislative system and education for public, medical professionals and legislators, with the establishment of an integrated infrastructure with policies and guidelines and financial and legislative support prior to establishing nationwide newborn screening (NBS).…”

Neurodevelopmental and Cognitive Outcomes of Classical Homocystinuria: Experience from Qatar

“…The use of sibling controls in this study is not novel, as a number of previous studies have used siblings as controls possibly for the same reasons mentioned above (Koch et al 1984;Eldridge et al 1989;Yap et al 2001). In 2003, Qatar has established an expanded newborn screening (NBS) programme for a number of metabolic and endocrine conditions including CHU (by using methionine) (Lindner et al 2007;Zschocke et al 2009;Gan-Schreier et al 2010). In 2006, NBS for CHU performed by measuring total homocysteine.…”

“…Clinically, CBS-deficient patients may present with ectopia lentis, osteoporosis, and skeletal deformities often associated with Marfanoid features, but most importantly with intellectual disability and life-threatening complications of the vascular system leading to premature death (Mudd 1985;Mudd et al 1985;Yap 2012). Therapy of homocystinuria usually includes administration of high doses of pyridoxine, the cofactor of CBS; however, only less than 50% of affected subjects show a substantial plasma homocysteine reduction (Mudd 1985;Lindner et al 2007;Yap 2012). The homocystinuria patients in Qatar are known to be pyridoxine nonresponsive with more severe phenotype and complications (El-Said et al 2006;Zschocke et al 2009;GanSchreier et al 2010).…”

“…Consequently, an impaired CBS activity leads to hyperhomocysteinaemia and homocystinuria, hypermethioninaemia and hypocysteinaemia (Mudd 1985;Yap 2012). The human CBS gene, mapped to chromosome 21q21-3, encompasses 30 kb of genomic DNA, and a total of 23 exons have been reported (Lindner et al 2007). However, only exons 1-14 and 16 encode the CBS protein.…”

Newborn Screening for Vitamin B6 Non-responsive Classical Homocystinuria: Systematical Evaluation of a Two-Tier Strategy

“…Met and Phe were analyzed as their butyl esters on a triple quadrupole tandem mass spectrometer with [ 2 H 3 ]methionine and [ 2 H 3 ]phenylalanine as internal deuterated standards as previously described (Lindner et al 2007 and the references therein). All other participating laboratories performed amino acid and acylcarnitine profiling using the above-mentioned derivatization step and subsequent ESI-MS/MS measurements (Australia and Austria: Wilcken et al 2003;Taiwan: Huang et al 2006; and the Netherlands: Rizzo et al 2003).…”