No abstract

The article highlights the experience of the NBS Program in Saudi Arabia and providing data on specific regional incidences of all the screened disorders included in the programme; and showed that the incidence of these disorders is one of the highest reported so far world-wide.

This review presents the current experiences with newborn screening in the Middle East and North Africa region. The population in the region is about 400 million, with high birth rate and an estimated 10 million newborns per year. The majority of the population is of the Islamic faith and mostly Arab. The population is characterized by a high consanguinity (25-70%) and a high percentage of first-cousin marriages. Haemoglobin disorders, inherited metabolic disorders, neurogenetic disorders and birth defects are relatively common among the population. There is a rather slow progress in developing and implementing preventive genetic programmes owing to legal, cultural, political and financial issues. Although research spending is rather soft in the region, there are numerous pilot studies that highlighted the high incidence of genetic defects and the need for newborn screening programmes. Currently, there are only four countries that are executing national newborn screening but they vary from one disease to 23 and coverage is not complete. The region needs to take big steps towards developing national strategies for prevention and should learn from experiences of regional and international screening programmes.

We ascertained a patient with the full-blown phenotype of isolated sulfite oxidase deficiency in a consanguineous Arab family. The proband's phenotype included the presence of intractable seizures in the neonatal period, some dysmorphic features, neuroradiologic findings reminiscent of hypoxic ischemic encephalopathy and rapidly progressive brain destruction leading to severe neurodevelopmental impairment. Biochemically, the patient excreted a large amount of S-sulfocysteine with normal amounts of xanthene and hypoxanthine and had normal plasma uric acid, which was consistent with isolated sulfite oxidase deficiency. We report the identification of the first Arab mutation in SUOX, the gene for sulfite oxidase enzyme, in the ascertained family. The newly identified Arab mutation in the SUOX gene (a single nucleotide deletion, del G1244) is predicted to cause a frame shift at amino acid 117 of the translated protein with the generation of a stop codon and total truncation of the molybdo-pterin- and the dimerizing-domain(s) of SUOX protein expressed from the mutant allele. The identification of this new Arab SUOX mutation should facilitate pre-implantation genetic diagnosis and selection of unaffected embryos for future pregnancy in the ascertained family with the mutation and related families with the same mutation.

Molybdenum cofactor and isolated sulphite oxidase deficiencies are two related rare autosomal recessive diseases characterized by severe neurological abnormalities, dislocated lens and mental retardation. Determination of three biochemical markers S-sulphocysteine (SSC), xanthine (XAN) and hypoxanthine (HXAN) in urine is essential for a definitive diagnosis and identification of the exact defect. We developed a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of SSC, XAN and HXAN in urine. The analysis was carried out in the negative-ion selected-reaction monitoring mode. The turnaround time for the assay was 7 min. Linear calibration curves for the three biomarkers were obtained in the range of 12-480 micromol/L. The intra- and inter-day assay variations were <2.5%. Mean recoveries of SSC, XAN and HXAN added to urine at two significantly different concentrations were in the range 94.3-107.3%. At a normal SSC urine excretion value of 3.2 micromol/mmol creatinine, the signal-to-noise ratio was 337:1. This stable isotope dilution LC-MS/MS method is specific, rapid and simple, and provides definitive diagnosis for molybdenum cofactor and isolated sulphite oxidase deficiencies in very small volumes of urine. We have identified seven new cases of isolated sulphite oxidase deficiency from four Saudi families and one Sudanese family.