الفهرس 
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Abstract
SUMMARY
MS is a powerful technology that allows a rapid and sensitive screening over more than 30 genetic disorders of amino acid, fatty acid and organic acid disorders through measurements of amino acids and acylcarnitines in a single dried blood spot.
IEM are a heterogeneous group of inherited disorders that are individually rare but collectively common; and they should be considered in any critically ill neonate.
Early detection of IEM, during the presymptomatic stage, and introduction of a proper treatment reduces morbidity and mortality rates among affected infants.
IEM are single gene disorders with an autosomal recessive inheritance in most of them. Consanguinity increases the incidence of autosomal recessive disorders and consequently IEM.
In the early 1960s, Guthrie developed the first newborn screening program aiming at screening the whole population for PKU; using Guthrie bacterial inhibition assay. Because of the relative insensitivity of Guthrie test it had been gradually replaced by other techniques such as spectrofluorometry and immunoassay.
With the introduction of the new technology of tandem mass spectrometry (MS/MS) by the mid 1990’s, a new screening concept had emerged “one test many disorders” instead of, that previously known, “one test one disorder”
In the United States, more than 4 million newborns are screened annually for a panel of 29 core conditions as recommended by the American College of Medical Genetics (ACMG) in 2006.
National NBS programs had been established in only few countries in the Middle East region including Saudi Arabia and United Arab of Emirates; they are mainly directed to amino acid, organic acid, fatty acid disorders and congenital hypothyroidism.
In Egypt, M.O.H. implemented a neonatal screening program for congenital hypothyroidism, in 2000. There are few available studies aiming at direct estimation and diagnosis of IEM using TMS technology among Egyptians.
Tandem mass spectrometry (MS/MS) coupled to chromatographic techniques such as LC or GC has become reliable, fast andmoney saving analytical technique in clinical and non-clinical aspects. In Newborn screening, LC- MS/MS can be adjusted to operate in several modes; namely, Precursor ion mode, Product ion mode, Neutral loss mode and Multiple Reaction Monitoring mode (MRM).
Amino acid and acylcarnitine profiles may be affected by several factors including the nutritional status of the patient, blood transfusion, and drugs. Consequently, interpretation of results depends on pattern recognition, rather than on individual abnormal values.
During the period from January 2013 to July 2013, 486 critically ill neonates had been enrolled in this study; 238 females and 248 males. The patients were collected from 3 different busy NICU and those referred to GUASH for neonatal screening. Patients’ data were recorded from files prior to blood sampling. Samples were processed using a non-derivatised method before their introduction in the LC-MS/MS.
Positive results were followed by confirmatory investigations. Once the diagnosis of IEM has been established, the proper treatment was given to the patients, who were clinically followed up during their NICU stay and after their discharge.
The results showed that the incidence of IEM among critically ill neonates was 2.3 %. Six different disorders; MSUD, NKH, IVA, Tyr-1, MMA and GA-1, were detected during the study with the highest incidence (45%) for MSUD. Finally, we are in need of implementation of a national new born screening program using TMS technology aiming at actual estimation of incidence, diagnosis and management of IEM in Egypt.