Genetic disorders (PKU, and Cystic Fibrosis) - PowerPoint Presentation

1. Genetic disorders (PKU, and Cystic Fibrosis) Supervised by: Dr. Nuhad Alduri Prepared by : zahraa basim mohammed

2. PhenylketonuriaPhenylketonuria, an inborn error of metabolism inherited as an autosomal recessive trait (the PAH gene is located on chromosome 12q24), is caused by a deficiency or absence of the enzyme needed to metabolize the essential amino acid phenylalanine. Classic PKU is at one end of a spectrum of conditions known as hyperphenylalaninemia. -In PKU, the hepatic enzyme phenylalanine hydroxylase, which normally controls the conversion of phenylalanine to tyrosine, is deficient. This results in the accumulation of phenylalanine in the bloodstream and urinary excretion of abnormal amounts of its metabolites, the phenyl acids .One of these phenylketones, phenylacetic acid, gives urine the characteristic musty odor associated with the disease.

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4. Tyrosine, the amino acid produced by the metabolism of phenylalanine, is absent in PKU. Tyrosine is needed to form the pigment melanin and the hormones epinephrine and T4 . Decreased melanin production results in similar phenotypes of most individuals with PKU, which is blond hair, blue eyes, and fair skin that is particularly susceptible to eczema andother dermatologic problems. Children with a genetically darker skin color may be red haired or brunette.

5. . The prevalence of PKU ,The reported figures for PKU in the United States is 1 case per 15,000 live births. The disease has a wide variation of incidence by ethnic groups. In Europe, the incidence is 1 in 10,000 births; in Asia and Africa, the prevalence is quite low. Clinical manifestations in untreated PKU include failure to thrive (growth failure); frequent vomiting; irritability; hyperactivity; and unpredictable, erratic behavior. Cognitive impairment, cystic degeneration of the gray and white matter, and disturbances in cortical lamination. Older children commonly display bizarre or schizoid behavior patterns such as fright reactions, screaming episodes, head banging, arm biting, disorientation, failure to respond to strong stimuli, and catatonia-like positions.

6. The objective in diagnosing and treating the disorder is to prevent cognitive impairment. The most commonly used test for screening newborns is the Guthrie blood test . this test detects serum phenylalanine levels greater than 4 mg/dl (normal value, 1.6 mg/dl). -Other methods for testing include quantitative fluorometric assay and tandem mass spectrometry. Only fresh heel blood, not cord blood, can be used for the test. Best results are obtained by collecting the specimen with a pipette from the heel stick and spreading the blood uniformly over the blot paper. Because of the possibility of variant forms of hyperphenylalaninemia, -PKU cofactor variant screen should be performed in all children diagnosed with PKU .

7. Therapeutic Management*Treatment of PKU involves restricting phenylalanine in the diet. Because the genetic enzyme is intracellular, systemic administration of phenylalanine hydroxylase is of no value.Phenylalanine cannot be eliminated because it is an essential amino acid in tissue growth. Therefore, dietary management must meet two criteria: (1) meet the child's nutritional need for optimum growth and (2) maintain phenylalanine levels within a safe range (2 to 6 mg/dl in neonates and children up to 12 years old, and 2 to 10 mg/dl through adolescence)

8. The daily amounts of phenylalanine are individualized for each child and require frequent changes on the basis of appetite, growth and development, and blood phenylalanine and tyrosine levels. Because all natural food proteins contain phenylalanine and will be limited, the diet must be supplemented with a specially prepared phenylalanine-free formula .The phenylalanine-free formula is an amino acid-modified formula essential in the low phenylalanine diet to provide the appropriate protein, vitamins, minerals, and calories for optimal growth and development. Because tyrosine becomes an essential amino acid, the phenylalanine-free formula supplies an adequate amount . When treatment for PKU was first instituted, it was believed that phenylalanine withdrawal during only the first 3 years of age would suffice to avoid cognitive impairment and other deleterious manifestations of PKU.

9. However, most clinicians now agree that to achieve optimal metabolic control and outcome, a restricted phenylalanine diet, including medical foods and low protein products, most likely will be medically required for virtually all individuals with classic PKU for their entire lives Such lifetime reduction of phenylalanine intake is necessary to prevent neuropsychological and cognitive deficits because even mild hyperphenylalaninemia (20 mg/dl) would produce such effects. including cognitive impairment, cardiac defects, and LBW. It is recommended that phenylalanine levels below 6 mg/dl be achieved at least 3 months before conception in women with PKU

10. PrognosisAlthough many individuals with treated PKU manifest no cognitive and behavioral deficits, many comparisons of individuals with PKU with control participants show lower performance on IQ tests, with larger differences in other cognitive domains; however, their performance is still in the average range. Evidence for differences in behavioral adjustment is inconsistent despite anecdotal reports suggesting greater risk for internalizing psychopathology and attention disorders. Recent data suggest that treatment with tetrahydrobiopterin in addition to the phenylalanine-restricted diet may be beneficial to PKU patients .Total bone mineral density is considerably lower in children who are on a low-phenylalanine diet even though calcium, phosphorus, and magnesium intakes are higher than normal.

11. Nursing Care ManagementThe principal nursing considerations involve teaching the family regarding the dietary restrictions Foods with low phenylalanine levels (e.g., vegetables, fruits, juices, and some cereals, breads, and starches) must be measured to provide the prescribed amount of phenylalanine. High-protein foods, such as meat and dairy products, are eliminated from the diet. The sweetener aspartame (NutraSweet) should be avoided because it is composed of two amino acids, aspartic acid and phenylalanine, and if used will decrease the amount of natural phenylalanine that is prescribed for the day. Maintaining the diet during infancy presents few problems. Solid foods such as cereal, fruits, and vegetables are introduced as usual to the infant. Difficulties arise as the child gets older.

12. The child's increasing independence may also inhibit absolute control of what he or she eats. Either factor can result in decreased or increased phenylalanine levels. Parents need a basic understanding of the disorder and practical suggestions regarding food selection and preparation.* Meal planning is based on weighing the food on a gram scale; a less accurate method is the exchange list. As soon as children are old enough, usually by early preschool, they should be involved in the daily calculation, menu planning, and formula preparation. Preparation of the phenylalanine-free formula can present some challenges. The formula tends to be lumpy; mixing the powder with a small amount of water to make a paste and then adding the rest of the required liquid, helps alleviate this problem. Some of the complete formulas are chocolate, vanilla, strawberry, and orange flavored. Incomplete formulas are also available that do not contain the vitamins and minerals and are plain tasting; these can be added to cold foods instead of mixing them as a formula. Family Support + In addition to the problem related to a child with a chronic disorder the parents have the burden of knowing that they are carriers of the defect.

13. Cystic Fibrosis

14. Cystic FibrosisCF is a life-shortening disease, inherited as an autosomal recessive trait. The affected child inherits the defective gene from both parents, with an overall risk of one in four if both parents carry the gene.

15. Pathophysiologyhe primary factor, and the one that is responsible for many of the clinical manifestations of the disease, is mechanical obstruction caused by the increased viscosity of mucous gland secretions Instead of forming a thin, freely flowing secretion, the mucous glands produce a thick mucoprotein that accumulates and dilates them. Small passages in organs (such as the pancreas and bronchioles) become obstructed as secretions precipitate or coagulate to form concretions in glands and ducts. The earliest postnatal manifestation of CF is often meconium ileus in the newborn, in which the small intestine is blocked with thick, puttylike, tenacious, mucilaginous meconium

16. In the pancreas, the thick secretions block the ducts, eventually causing pancreatic fibrosis. This blockage prevents essential pancreatic enzymes from reaching the duodenum, which causes marked impairment in the digestion and absorption of nutrients. -CFRD is reported to be the most common complication associated with CF. -A common gastrointestinal complication associated with CF is prolapse of the rectum. -Pulmonary complications are present in almost all children with CF, but the onset and extent of involvement are variable.

17. -The reproductive systems of both males and females with CF are affected. -Fertility can be inhibited by highly viscous cervical secretions. -Women with CF who become pregnant have an increased incidence of premature labor and delivery and infant low birth weight. -Growth and development are often affected in children with moderate to severe forms of CF.

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19. Clinical Manifestations of Cystic FibrosisMeconium Ileus*-Abdominal distention-Vomiting-Failure to pass stools-Rapid development of dehydration

20. Gastrointestinal Manifestations-Large, bulky, loose, frothy, extremely foul-smelling stools-Voracious appetite (early in disease)-Loss of appetite (later in disease)-Weight loss-Marked tissue wasting -Failure to grow-Distended abdomen-Thin extremities-Sallow skin-Evidence of deficiency of fat-soluble vitamins A, D, E, and K-Anemia

21. Pulmonary Manifestations Initial signs:-Wheezy respirations-Dry, nonproductive coughEventually:-Increased dyspnea-Paroxysmal cough-Evidence of obstructive emphysema and patchy areas of atelectasisProgressive involvement:-Overinflated, barrel-shaped chest-Cyanosis-Clubbing of fingers and toes-Repeated episodes of bronchitis and bronchopneumonia

22. Diagnostic Evaluation... -The diagnosis of CF was based on the presence of one or more characteristic features (chronic sinopulmonary disease, gastrointestinal or nutritional abnormalities , salt loss syndromes, -history of CF in a sibling or a positive newborn screen plus laboratory confirmation of an abnormality in the CFTR gene or protein. -immunoreactive trypsinogen (IRT) indicates persistent hypertrypsinogenemia and does not diagnose CF but identifies infants at risk of CF.-sweat chilorde test collecting the sweat on filter paper, and measuring the sweat electrolytes. Normally, sweat chloride content is less than 40 mEq/L, with a mean of 18 mEq/L. A

23. Therapeutic Management Goals of CF therapy:- 1-prevent or minimize pulmonary complications.2-prevent chronic pseudomonas infection.3-encourage appropriate physical activity. 4-promote a reasonable quality of life for the child and the family.

24. Management of Pulmonary Problems1-prevention and treatment of pulmonary infection.-improving ventilation, -removing mucopurulent -secretions -administering antimicrobial agents 2-Airway clearance therapies (ACTs) -percussion -postural drainage, -positive expiratory pressure (PEP), -active-cycle-of-breathing technique, -autogenic drainage, -oscillatory PEP, -high-frequency chest compressions (HFCCs), -exercis

25. 3-Bronchodilator medication 4-Nebulized hypertonic saline (7%) has been shown to be effective in improving airway hydration and increases mucus clearance.5-IV antibiotics may be administered. 6-Oxygen administration 7-bleeding can be controlled with -bed rest -IV antibiotics -replacement of acute blood loss, -IV conjugated estrogens (Premarin) or vasopressin (Pitressin) -vitamin K or fresh-frozen plasma 8-Treatment of nasal polyps

26. Management of Gastrointestinal Problems The principal treatment for pancreatic insufficiency is:- replacement of pancreatic enzymes, which are administered with meals and snacks to ensure that digestive enzymes are mixed with food in the duodenum. -Children with CF require a well-balanced, high-protein, high-caloric diet (because of their impaired intestinal absorption). -Growth failure despite adequate nutritional support may indicate deterioration of pulmonary status. -manage rectal prolapse occurs in a small number of infants with CF. - Children with CF often experience transient or chronic gastroesophageal reflux.

27. Management of Endocrine Problems *Children with CFRD -require close monitoring of blood glucose -administration of insulin, -diet -exercise management, -quarterly glycosylated hemoglobin (A1C) measurements *Children with CFRD should perform self-blood glucose monitoring (SBGM) three times daily and should be on an insulin regimen. *During acute CF exacerbations, the nondiabetic child should be monitored closely for hyperglycemia

28. Nursing Care Management -Pulmonary assessment is the same as that described for asthma, with special attention to lung sounds, observation of cough, and evidence of decreased activity or fatigue. -Gastrointestinal assessment primarily involves observing the frequency and nature of the stools and abdominal distention. -The nurse should also be alert to evidence of growth failure -The nurse assesses the newborn for feeding and stooling patterns .-The nurse also participates in diagnostic testing, such as the initial newborn screening, DNA analysis, or sweat chloride test.

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