الفهرس 
HISTORY OF NEONATAL SCREENINGOnly 14 pages are availabe for public view
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Abstract
Newborn screening is one of the first and largest population-based disease intervention programs. These programs were initially designed to detect infants with possible inborn errors of metabolism which are genetically determined and typically inherited in an autosomal recessive pattern.
Dr. Robert Guthrie developed the first simple, sensitive, and inexpensive screening test for hyperphenylalanemia in 1962. With this test phenylalanine, in blood dried on filter paper, inhibits bacterial growth. The three main laboratory methods used for population-based screening of newborns for PKU are the Guthrie Bacterial Inhibition Assay (BIA), fluorometric analysis, and tandem mass spectrometry.
Many countries have since expanded their programs to include other non-metabolic disorders, such as hematological disorders and endocrinopathies. If screening is positive or results are unusual, additional testing is performed to confirm the diagnosis. After the diagnosis is confirmed, medical interventions, usually consisting of special diets, vitamins, or pharmacological treatment, are initiated.
Infants and children are then followed over time to confirm effectiveness of treatment. Comprehensive lifelong services are essential to those infants with chronic disease and their families.
Early detection of these disorders before irreversible organ damage occurs may lead to more effective treatment and more favorable outcomes. For example, there is an inverse relationship between the age at the start of treatment and intelligence quotient in infants diagnosed with congenital hypothyroidism.
Early clinical signs of metabolic disorder are nonspecific and difficult to distinguish in infants. Some disorders are asymptomatic in the neonatal period and present later in life. Metabolic disease mimics many other conditions; often the healthcare provider may not immediately indentify as IEM are perceived as rare disorders. In some disorders, such as hyperphenylalaninemia, there are no early symptoms at all.
The newest technology available for newborn screening is tandem mass spectrometry (MS / MS), which allows for the addition of tests to identify more than 20 inborn errors metabolism to previously available screening panels. MS/MS is based on the identification of amino acids and acyl-carnitine. This method is particularly elegant as both amino acids and acyl-carnitine can be extracted from the filter paper blood spot and measured in the same sample in a very short time by altering the scanning modes that have been automatically set by the software.
Galactosemia must be rapidly excluded in infants with early onset cholestasis by measuring enzymes activity, urine analysis for reducing substance is important.
Organic acid disorders potentially identifiable by MS/MS technology include glutaric acidemia type 1 & 2, isovaleric acidemia, methylmalonic acidemia, propionic acidemia, and some disorders of ketogenesis and ketolysis. Multiple CoA-carboxylase deficiency also can be detected.
Tandem mass spectrometry permits earlier collection of specimens, provides immediate and accurate determination of the leucine/alanine ratio, all of which should allow diagnosis and initiation of therapy for maple syrup urine disease and other organic acid and amino acid disorders between 3 and 5 days of age.
The newborn screening test is a colorimetric assay for biotinidase on the dried filter paper blood spot. Confirmation of the diagnosis requires measuring biotinidase activity in serum, whole blood, or red cells
Most programs for newborn screening for homocystinuria are based on the detection of high methionine levels using the Guthrie bacterial inhibition assay.
The detection of fatty acid oxidation disorders, particularly medium-chain acyl-CoA dehydrogenase deficiency, represents a major advantage for MS/MS. After PKU, medium-chain acyl-CoA dehydrogenase deficiency was the most common disorder detected.
Neonatal screening programs for very long chain acyl-coenzyme A dehydrogenase deficiency have been implemented recently in various countries. Using electro-spray ionization tandem mass spectrometry allows detection of affected newborns and start of therapy before onset of neurological complications.
MS/MS is suggested as a first line screening strategy for detecting increased tyrosine concentrations in dried blood spots for screening of tyrosinemia. The second line test, an assay for succinylacetone, is recommended as a confirmatory test for increased tyrosine levels.
Traditional newborn screening for congenital adrenal hyperplasia (CAH) is based on measuring 17-hydroxy progesterone (17-OHP) by different immunoassays. To improve this situation, a new method developed MS/MS to measure 17-OHP, androstendione and cortisol simultaneously in blood spots. Early diagnosis and treatment of CAH prevents the adrenal crisis and early infant death and makes an earlier correct gender assignment possible
Congenital Hypothyroidism is a common endocrine disorder over the world. It is essential to detect this disorder early as it can be successfully treated and disability can be totally prevented. Babies detected by the screening were put on hormone replacement therapy and were followed. The results of treatment were 100% successful with no features of hypothyroidism.
Most programs use a two-fold process with the filter paper spot technique. A T4 measurement is followed by a measurement of TSH in specimens with low T4 values.
.Advances in DNA technology and mutation detection surely will increase the number of disorders for which we can perform primary mutation detection on dried blood spots, as for cystic fibrosis. Cystic fibrosis newborn screening involves measuring immunoreactive trypsinogen (IRT) in dried filter paper blood spot.
Glucose-6-phosphate dehydrogenase deficiency can be diagnosed with a quantitative spectrophotometric analysis or, more commonly, by a rapid fluorescent spot test.
The primary purpose of neonatal screening for hemoglobinopathies identify infants with sickle cell disease, for whom early diagnosis, parental education, prophylactic penicillin, and comprehensive medical care markedly reduce morbidity and mortality. A number of screening programs have started performing hemoglobin electrophoresis from the dried blood spot sample.
A number of screening programs have started performing electrophoresis for dried blood spot sample for the diagnosis of thalassemia.
Screening of hereditary spherocytosis can be done by blood film using gel electrophoresis and also DNA analysis.
The primary purpose of neonatal screening for hemoglobinopathies identify infants with sickle cell disease, for whom early diagnosis, parental education, prophylactic penicillin, and comprehensive medical care markedly reduce morbidity and mortality. A number of screening programs have started performing hemoglobin electrophoresis from the dried blood spot sample.
A number of screening programs have started performing electrophoresis for dried blood spot sample for the diagnosis of thalassemia.
Screening of hereditary spherocytosis can be done by blood film using gel electrophoresis and also DNA analysis.
The diagnosis of HIV infection is made by the detection of specific antibody by an enzyme-linked immunosorbent assay (ELISA) .Viral detection test must be used to identify infected infants born to HIV sero-positive mothers.
A neonatal screening programs for toxoplasmosis based on multiple serological tests which are necessary to confirm the diagnosis by detection of specific lgG, lgM, lgA, and lgE antibodies.
Early intervention for children with hearing loss is needed to maximize speech and language development. The ability to screen large numbers of children quickly and inexpensively relied on two additional technologic breakthroughs; evoked otoacoustic emission testing and automatic auditory brain stem response testing.
No laboratory tests are routinely required in infants of drug-abusing mothers, laboratory tests are required to rule out other causes of particular signs and symptoms, or to follow up and manage some particular complication of drug abuse.
Neonatal screening program for hypothyroidism began in Egypt in 2000 and became as a routine screening program and mandatory for all newborns in the first week of life through heel prick method.
Neonatal screening has shown as incidence of 1 per 3000 in Egypt . A blood DROP is obtained by heel prick on a filter paper and is analyzed for TSH and T4.
Screening for G6PD Mediterranean mutation among Egyptian neonates is not obligatory. Neonatal screening for genetic, metabolic and infectious diseases in Egypt is still underdeveloped and is just as small studies for researches purpose.