Chapter 55 Newborn Screening for Genetic Disorders
PATHOPHYSIOLOGY
Infants born with inborn errors of metabolism lack an enzyme essential in the body’s biochemical reactions, or have deficient amounts of it. All ingested food is broken down into fats, proteins, carbohydrates, vitamins, and minerals, and is then metabolized by enzymes. An enzyme deficiency, as seen with inborn errors of metabolism, prevents the usual chain of biochemical reactions, referred to as the metabolic pathway, from occurring properly. Instead, abnormal chains of metabolic substances are formed owing to a deficiency in the key, normally present enzyme, which can cause a number of untoward outcomes, as observed with inborn errors of metabolism. Box 55-1 presents numerous genetic disorders that are enzyme deficiencies. Most of these enzyme deficiencies are inherited as autosomal recessive traits; others (rarely) are transmitted as sex-linked or mitochondrial disorders.
Box 55-1 Inborn Errors of Metabolism
• Disorders of carbohydrate metabolism
• Disorders of galactose metabolism
• Disorders of fructose metabolism
• Carbohydrate malabsorption in the intestinal brush border
• Disorders of amino acid metabolism
• Disorders of histidine metabolism
• Amino acid transport disorders
• Branched-chain amino acid and keto acid disorders
• Organic acidemias: disorders of propionate and methylmalonate metabolism
• Disorders of pyruvate dehydrogenase complex
• Disorders of pyruvate carboxylase complex
• Pyruvate kinase and glucose-6-phosphatase deficiencies
• Disorders of lipid metabolism
• Familial hyperlipoproteinemia: familial lipoprotein lipase deficiency
Adapted from Theorell C, Degenhardt M: Assessment and management of metabolic dysfunction. In: Kenner C et al, editors: Comprehensive neonatal nursing: a physiologic perspective, ed 2, Philadelphia, 1998, WB Saunders.
Metabolic disorders in the newborn are not necessarily identified in the hospital, because the clinical manifestations may not become evident until weeks or even months later. Clinical manifestations can be specific or general, depending on the disorder. Metabolic disorders have been categorized into three types: (1) those that are “silent” or slowly manifest symptoms, such as phenylketonuria (PKU), and that if not treated early can result in mental retardation; (2) those such as urea cycle disorders or organic acidemias that manifest as an acute metabolic crisis shortly after birth (a few days), in which the infant demonstrates symptoms of respiratory distress, vomiting, and lethargy leading to coma, and which can be life threatening if not identified and treated; and (3) those that cause progressive neurologic disorders, such as Tay-Sachs disease. It is important that these disorders be detected and treated as soon as possible to prevent or minimize serious outcomes of developmental delays, learning disabilities, attention-deficit/hyperactivity disorder, or mental retardation. Widespread screening exists for the following inborn errors of metabolism: (1) PKU, (2) congenital hypothyroidism, (3) galactosemia, (4) maple syrup urine disease, and (5) congenital adrenal hyperplasia. Note that PKU, congenital hypothyroidism, and galactosemia are the only three newborn screening tests required by all states (Box 55-2).
Box 55-2 Newborn Screening Programs
Newborn screening is a general term for a nationwide program, governed by individual states, that uses a simple blood test called tandem mass spectrometry to screen for three categories of disorders: inborn errors of metabolism (e.g., PKU; galactosemia; maple syrup urine disease [MSUD]); hemoglobinopathies (e.g., sickle cell disease [see Chapter 71]; and hemophilia [see Chapter 32]); and endocrinopathies (e.g., congenital hypothyroidism; congenital adrenal hyperplasia; and cystic fibrosis (see Chapter 17). There are over 100 different tests that newborns could be screened with. A complete listing of the tests that are required by each state can be found at www.genes-r-us.uthscsa.edu/nbsdisorders.pdf. A list of resources is included at the end of this chapter for families who may wish to have optional testing done. This chapter focuses primarily on inborn errors of metabolism since sickle cell disease, hemophilia, and cystic fibrosis are covered elsewhere in this book. Newborn screening guidelines are available from the Health Resources and Services Administration of the U.S. Department of Health and Human Services, under the title “U.S. Newborn Screening System Guidelines II: Follow-Up of Children, Diagnosis, Management, and Evaluation: Statement of the Council of Regional Networks for Genetic Services (CORN)” (available from www.ask.hrsa.gov/detail.cfm?id=MCHN011).
In the future, gene-based therapy may offer promising options to correct the deficiency of the enzyme or substrate. Risk factors associated with inborn errors of metabolism include past family history of unexplained neonatal and/or sibling deaths, consanguinity, multiple spontaneous abortions, psychomotor difficulties in family members, and symptoms in previous children associated with metabolic diseases, such as metabolic acidosis, ataxia, and hypoglycemia.
INCIDENCE
1. Incidence is fewer than 1 in 10,000 births.
2. Of pregnancy losses, 60% are caused by genetic problems.
3. Of infant mortality, 20% to 30% are due to genetic defects, the leading cause of infant mortality.
4. Between 30% and 50% of postneonatal infant deaths are due to congenital anomalies.
5. Genetic defects are the fourth leading cause of diminished life span.
6. In most infants, autosomal recessive conditions will be identified by 1 month of age.
7. Incidence for certain disorders (e.g., sickle cell disease, Tay-Sachs disease, cystic fibrosis) is higher among specific ethnic groups.
CLINICAL MANIFESTATIONS
A number of presenting symptoms are linked with inborn errors of metabolism. Symptoms may be generalized, or manifestations may be specific. Clinical manifestations associated with selected disorders may include one or more of the following:
COMPLICATIONS
Complications will vary depending on when the enzyme deficiency was identified and treated.
LABORATORY AND DIAGNOSTIC TESTS
1. Initial newborn screen—to screen for genetic disorders (see Box 55-3)
2. Listed here are the laboratory tests most commonly used in addition to the initial newborn screen for the diagnosis of inborn errors of metabolism. Selection of tests will depend on the clinical presentation and severity of symptoms (refer to Appendix D for normal ranges).
3. In the event of infant death, the following tests should be performed to rule out undiagnosed inborn errors of metabolism as the cause of death:
MEDICAL MANAGEMENT
The first priority of medical therapy is to treat the infant who has life-threatening symptoms such as acute metabolic encephalopathy, with the goal of stabilizing the infant. Other acute episodes of illness the infant may experience involve metabolic acidosis, electrolyte disturbances, respiratory distress, intractable seizures, and sepsis. These critical problems require aggressive medical treatment such as exchange transfusion, venovenous hemofiltration, peritoneal dialysis, hemodialysis, and assisted ventilation. The goal of this phase of critical care is stabilization of the infant and prevention of complications.
The approaches to long-term treatment to manage enzyme disorders can be described in the following general terms. Dietary substances creating the toxic substrate, such as phenylalanine, are restricted or excluded from the diet. An enzyme replacement can be given for enzyme deficiencies, similar to thyroid replacement for hypothyroidism. An alternative metabolic pathway can be stimulated that circumvents the blocked metabolic pathway. Clinical status can be improved with the administration of high doses of vitamins (e.g., pyridoxine, biotin, vitamin B12). Enzyme therapy that involves replacing the deficient enzyme with a synthetic product is another treatment option. Depending on the diagnosis, a specific management plan for treatment will be instituted. Treatment plans will vary according to the particular syndrome and include nutritional therapy, such as administration of commercially prepared synthetic formulas; dietary supplementation; and, in some instances, invasive treatments such as splenectomy. Depending on the enzyme involved, bone marrow transplantation, liver transplantation, and gene therapy may be used to correct the metabolic disorder. Early detection and treatment are key to preventing or ameliorating the long-term effects of enzyme deficiencies.
NURSING ASSESSMENT
The purpose of the nursing assessment of the child with an inborn error of metabolism varies depending on the circumstances. During the diagnostic period, nursing assessment is focused on stabilization of the infant’s condition, diagnosis of the metabolic disorder, and initiation of the long-term treatment plan. Once the acute phase subsides, nursing assessment is directed to monitoring the child’s growth and development, the response to treatment, long-term effects, and family management of the child’s ongoing and long-term treatment plan. The assessment information listed below addresses the long-term components of care. Assessment parameters for the acute phase can be found in other chapters pertaining to the infant’s presenting symptoms, such as apnea or renal failure.
Ongoing nursing assessment of the child includes obtaining the nursing history and family pedigree (genogram); this includes gathering information on the family history of children with hypoglycemia, acute encephalopathy, metabolic acidosis, and psychomotor difficulties. Information is obtained on the mother’s pregnancy history, such as spontaneous abortions, previous pregnancies, and unexplained neonatal deaths.
1. Assess for dysmorphic features, including evaluation of the following:
2. Assess integumentary system.
3. Assess musculoskeletal system.
4. Assess for neurologic signs and symptoms.
5. Assess for other anomalies (not listed earlier).
6. Assess for signs of infection (fever, increased white blood cell count, septic shock).
7. Assess for skin breakdown from pruritus, malnutrition, edema, and decreased ability to heal.
8. Assess for malnutrition (lethargy, weakness, poor feeding, decreased appetite, vomiting, failure to gain weight, inadequate caloric intake).
9. Assess child’s comfort level (see Appendix I).
10. Assess coping responses and child’s level of activity, and provide therapeutic environment for child.
11. Assess family’s ability to manage child’s long-term care and to access community-based services, and provide supportive measures as indicated (see Appendix G).
12. Assess for developmental delay, achievement of growth and development milestones, and age at which milestones are achieved (see Appendix B).
NURSING DIAGNOSES
• Body temperature, Risk for imbalanced
• Intracranial adaptive capacity, Decreased
• Tissue perfusion, Ineffective
• Respiratory function, Risk for ineffective
• Nutrition: less than body requirements, Imbalanced
• Family processes, Interrupted
• Growth and development, Delayed
NURSING INTERVENTIONS
Care During Acute Phase
1. Monitor clinical status and immediately report any changes.
2. Maintain cardiorespiratory stability.
3. Monitor neurologic status with serial measures.
4. Monitor and maintain appropriate fluid, nutrient, and caloric intake.
5. Assess for signs of infection and implement preventive measures.
Ongoing and Long-Term Care
1. Monitor for adequate caloric intake and growth over time.
2. Promote growth and development by integrating play and positive stimulation into care routine (see Appendix B).
3. Facilitate integration of infant into his or her family.
4. Refer family to genetic specialists, because genetic counseling is advisable in view of genetic factor(s) associated with inborn errors of metabolism. If parents are planning for additional children, they may benefit from information about heritable nature of this child’s condition.
Discharge Planning and Home Care
1. Evaluate readiness for discharge. Factors to assess include the following:
2. Provide discharge instruction for parents covering the following:
3. Provide follow-up to monitor ongoing cardiorespiratory, neurologic, nutritional, developmental, and other specialized needs.
4. Refer as needed for counseling and other support resources.
American Academy of Pediatrics, Committee on Bioethics. Ethical issues with genetic testing in pediatrics. [AAP Policy (serial online)] http://aappolicy.aappublications.org/cgi/reprint/pediatrics;107/6/1451.pdf. Accessed May 7, 2006
Banta-Wright SA, Steiner RD. Tandem mass spectrometry in newborn screening: A primer for neonatal and perinatal nurses. J Perinat Neonatal Nurs. 2004;18(1):41.
Bryant KG, et al. A primer on newborn screening. Adv Neonatal Care. 2004;4(5):306.
Department of Health and Human Services, Centers for Disease Control and Prevention. Quality assurance and proficiency testing for newborn screening. (website) www.cdc.gov/nceh/dls/newborn_screening.htm Accessed May 8, 2006
Health Resources and Services Administration of the U.S. Department of Health and Human Services. U.S. Newborn screening system guidelines II: Follow-up of children, diagnosis, management, and evaluation: Statement of the Council of Regional Networks for Genetic Services (CORN). (website) www.ask.hrsa.gov/detail.cfm?id=MCHN011 Accessed May 9, 2006
National Newborn Screening and Genetics Resources Center. National newborn screening status report. (website) http://genes-r-us.uthscsa.edu/nbsdisorders.pdf Accessed May 8, 2006
Theorell C, Degenhardt M. Assessment and management of the metabolic system. Kenner C, et al. Comprehensive neonatal nursing: a physiologic perspective, ed 3, Philadelphia: WB Saunders, 2003.
