1. Genetic Diseases

2. Analytical methods for the identification of genetic disease play an important part in the pediatric clinical chemistry laboratory. The presentation of many genetic diseases are unique to the pediatric population and require physicians and clinical laboratorians who provide services to have specialized knowledge and training. most diseases that present with clinical signs in infants and children are inherited in an autosomal recessive mode. Parents are almost always without any symptoms.

3. Certain other diseases are recessive but are inherited on the X chromosome. Typically, boys inherit a mutated X chromosome from their mothers; because they do not inherit a paternal X chromosome, they show signs of disease with only one mutation. Girls carrying an X chromosome mutation may also demonstrate disease signs due to the fact that one of their X chromosomes becomes inactivated and if the active chromosome carries the mutation they will have the disease.

4. dominantly inherited diseases, which can be inherited as a single mutation through either parental line, frequently tend not to present as unique childhood diseases. Examples include familial hypercholesterolemia, Huntington disease, and factor Leiden thrombophilia, all of which are regarded as diseases of the adult population, although the mutation is inherited at birth. All these examples are diseases of DNA that replicates in the cell nucleus.

5. Mitochondrial DNA Mitochondria, the organelles responsible for generating cellular energy and other important metabolic pathways, also contain DNA(mtDNA), which encodes proteins involved in energy generation. mtDNA has a high rate of spontaneous mutation and results in a large number of energy-wasting diseases, many of which present with high blood lactate levels. Mitochondria are only inherited from the mother, so that mtDNA mutations that are not spontaneous can only come from the maternal lineage.

6. Cystic Fibrosis Cystic fibrosis(CF) is one of the most commonly inherited genetic diseases encountered by pediatric clinical chemistry laboratories. Its rate is 1of 2400 live births. CF results from recessively inherited mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. Patients in the newborn period may present with severe pancreatic insufficiency caused by accumulated thick mucous secretions in the pancreatic ducts, which inhibit the secretion of pancreatic digestive enzymes. These babies have steatorrhea and fail to thrive.

7. Patients with CF do not always develop pancreatic symptoms, however, in most patients, the thick mucus that accumulates in the lungs causes respiratory disease and makes them susceptible to rare infectious diseases such as Pseudomonas. CF is still regarded as untreatable. Diagnostic test involves measurement of chloride content in sweat collected after administration of pilocarpine. Molecular testing is also available, but many different mutations exist.

8. Newborn screening for Whole Population Certain inherited diseases are sufficiently common in the population to be considered candidates for whole population screening. Phenylketonuria was the first genetic metabolic disorder to be screened in every baby. other diseases that are readily treatable were added to the list in following years, including 21-hydroxylase deficiency, sickle cell disease and galactosemia. These diseases respon well to simple therapy, often, dietary. Tandem mass spectrometric analysis allows many different genetic diseases to be screened on a single sample at the same time.

9. Drug Metabolism and Pharmacokinetics There are several important differences in the way that infants and children handle pharmacologic agents compared with adults. Drug metabolism depends on absorption, volume of distribution, metabolism and clearance. syrups provide a more rapid release of a drug and greater availability for GIT absorption than tablets. The pH of gastric secretions differ, at birth, the gastric pH is neutral which can affect the absorption of some drugs including penicillins.

10. The distribution of drug often differs between adults and children, lipid soluble drugs reach a higher level more quickly and the drug is cleared more rapidly. It is appropriate to provide drugs in smaller, more frequent doses to optomize the effect. Hepatic metabolism of many drugs is immature in young infants. This may delay the metabolic conversion to an active drug, good hepatic as well as renal functions are important for clearing drugs.

11. Therapeutic Drug Monitoring The principles of TDM remain the same in adult and pediatric clinical chemistry. It is important to measure the blood levels of various drugs if that information can provide important guidance to the physician with regard to optimal dosing and to avoid both ineffective or toxic doses. Examples of drugs which require monitoring; phenytoin, phenobarbital, theophylline, methotrexate and gentamicin.

12. Toxicological Issues in Pediatric Clinical Chemistry The provision of a toxicologic service can be delivered into two distinct groups in pediatrics The first group involves infants and young children who unknowingly consume pharmacologic and other chemical agents. This usually involves the child finding access to medication belonging to another individual in the household and consuming the medication as if it were candy. The second group involves infants and children who consume overdoses of any drug or chemical agents. In both conditions toxicologic investigations should be carried out.