Tyrosinemia Type 1: an Overview of Nursing Care

Home , Porphobilinogen, Tyrosinemia

Continuing Nursing Education Objectives and instructions for completing the evaluation and statements of disclosure can be found on page 67.

Tyrosinemia Type 1: An Overview of Nursing Care

Elizabeth Barnby

umarylacetoacetate hydrolase (FAH) deficiency or tyrosinemia Tyrosinemia type 1 (TT1) is an inherited metabolic disease that can be fatal when type 1 (TT1) is an inherited not detected early by newborn screening. In the past, children with TT1 had a poor metabolic disease that can prognosis due to organ failure and neurologic crisis during infancy. Recent Fcause neurologic crisis and respiratory improvements in newborn screening have changed the prognosis of affected chil- distress. An inborn error of metabo- dren. Measurement of succinylacetone by tandem mass spectrometry provides lism, TT1 is a rare disease with a early identification and the opportunity to manage TT1 as a chronic disease. worldwide incidence of approximate- Treatment includes genetic counseling, dietary management, pharmacotherapy, ly one to two cases per 100,000 births, metabolic crisis prevention, and whole organ transplant. Nursing care is critical to although in some populations, the successful management when it is based on a clear understanding of the patho- incidence is much higher (Scott, physiology. This overview of nursing care will provide specific recommendations to 2006). It is a life-threatening disorder reduce complications and enhance the quality of life for children with TT1. that is usually fatal before two years of age if not treated effectively. Larochelle et al. (1967) described TT1 in infants TT1 (McHugh et al., 2011; Schunemann The deficiency is caused by a mutation presenting with a painful neurologic et al., 2008). When TT1 is identified on chromosome 15q23-25 (Nyhan, disorder that was associated with by enhanced newborn screening Barshop, & Ozand, 2005; Paradis, ascites, liver failure, failure to thrive, methods, the disease is treatable 1996). The disease is an autosomal coagulopathy, rickets, renal disease, (Turgeon et al., 2008). If not identified recessive disorder that is expressed and a cabbage-like odor. Since first on newborn screening, children with when a child receives the trait or described in the Canadian popula- the disease can present critically ill in mutation from both parents. In the tion, much has been learned about metabolic acidosis. Children with carrier state, the mutation is harmless the disease. In the Saguenay Lac-St. inborn errors of metabolism are iden- but can be passed on to offspring. Jean region of Quebec, Canada, the tified post-mortem when newborn An interruption in the tyrosine incidence is approximately one case screening fails to identify the disease catabolic pathway causes a metabolic per 1846 births (De Braekeleer & in the neonate (Bennett & Rinaldo, gridlock in the human body with Larochelle, 1990; Paradis, 1996). 2001; CDC, 2003; Chace et al., 2001). toxic substances accumulating in tis- There is reliable evidence that inborn Early identification and diagnosis are sues throughout the body. Treatment errors of metabolism contribute to life-saving for these metabolically can prevent the accumulation of these incidence of sudden infant death syn- unstable patients. The pediatric nurse toxic substances. The combination of drome (SIDS), although actual num- needs to understand the pathophysi- improvements in newborn screening bers are difficult to quantify (Bennett ology of the disease and nursing inter- and pharmacotherapy has improved & Rinaldo, 2001; Centers for Disease ventions that will improve patient outcomes (Nobili et al., 2010). Control and Prevention [CDC], 2003; outcomes to successfully intervene. The FAH enzyme at the terminal Hunt & Hauck, 2006). An overview of the pathophysiology end of the tyrosine catabolic pathway Mandatory newborn screening and nursing care will enhance out- is crucial to the breakdown of tyro- saves lives, and diagnostic accuracy comes when applied at the bedside. sine. When it is absent, toxic metabo- improves outcomes for children with lites higher up the pathway accumu- Pathophysiology late and cause disease (Scott, King, & Trahms, 2008). Occasionally, a sponta- Elizabeth Barnby, DNP, ACNP-BC, RN, is a TT1 is characterized by the child’s neous mutation can occur that pro- Clinical Assistant Professor and Under - inability to break down tyrosine. duces pockets of normal enzyme activ- graduate Program Director, University of Tyrosine is an essential amino acid ity, and this produces variable pheno- Alabama Huntsville, Huntsville, AL. contained in protein that the body typic expression (Nakamura, Tanaka, Acknowledgment: This work would not have needs to perform cellular functions. Mitsubuchi, & Endo, 2007). Because been possible without the wise guidance of Normally, the enzyme fumarylace- phenotypic expression varies, two Dr. Karen Frith. toacetate hydrolase (FAH) catalyzes children with the exact same chromo- Statements of Disclosure: Please see page tyrosine, but children with TT1 have a somal mutation can have varying 67 for statements of disclosure. deficiency of this essential enzyme. degrees of disease severity.

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FAH deficiency leads to an accu- Treatment ness. Succinylacetone inhibits conver- mulation of fumarylacetoacetate, sion of Delta-aminolevulinic acid to maleylacetoacetate, succinylacetoace- Children with TT1 must main- porphobilinogen in the heme synthe- tone, and succinylacetone. Maley - tain strict metabolic control of their sis pathway. Delta-aminolevulinic lacetoacetate causes renal tubular dys- disease. Parents play a key role in acid is neurotoxic. The symptoms are function in a Fanconi-like syndrome metabolic control by maintaining similar to the symptoms of porphyria. of renal failure and vitamin D-resist- dietary restriction of protein con- Lead is also an inhibitor of the con- ant rickets (Jacobs, van Beurden, sumption and avoidance of protein version of Delta-aminolevulinic acid. Klomp, Berger, & van den Berg, 2006). catabolism (Ashorn, Pitkanen, Salo, & Inhibition of the pathway causes neu- Fumarylacetoacetate and maleylace- Heikinheimo, 2006). Typical treat- ropathy, neurologic crisis, paralysis, toacetate cause hepatocyte injury that ment requires intensive developmen- and respiratory distress (Mitchell et can result in end stage liver disease, tally appropriate patient and family al., 1990). Mental retardation and bleeding, and hepatocellular carcino- education. An age-appropriate guide seizure disorders have also been ma (Orejuela, Jorquera, Bergeron, is useful to address these educational reported in children with errors in the Finegold, & Tanguay, 2008). Succiny- needs (see Table 1). metabolism of tyrosine (Palmer, 2006; lacetone is an inhibitor of the heme Avoiding protein catabolism is Rocha et al., 2000). With careful med- synthesis pathway, causing neurotox- difficult in the presence of an acute ical management and nursing care, icity that is similar to lead poisoning viral illness. When unable to eat, the this complication is preventable. The or aminolevulinic acid dehydratase body naturally breaks down protein ability to prevent neurologic deficits (ALAD) deficiency porphyria (Wyllie stores to maintain homeostasis. The offers financial and ethical incentive & Hyams, 2006). The neurotoxicity breakdown of protein causes the level to maintain high quality newborn can cause muscle paralysis and respi- of amino acid tyrosine to rise and screening for the disease (Bailey, ratory arrest (Krous, 2010; Turgeon et results in a metabolic crisis (Claudius, Skinner, & Warren, 2005). al., 2008). Fluharty, & Boles, 2005). Neurologic crisis is preventable if During fasting, the body pro- the family is educated and health care Diagnosis duces ketones. Urine ketones can be providers respond appropriately to used as a metabolic indicator of pro- the metabolic crisis. The most impor- Newborn screening for TT1 is tein catabolism. Ketones are a break- tant way to prevent neurologic crisis performed by tandem mass spectrom- down product of fatty acid metabo- is prompt administration of IV glu- etry. Tandem mass spectrometry is an lism. Ketones in the urine should be cose solutions, usually 10% or higher accurate way to measure newborn managed as an emergency. When depending on severity of symptoms blood spot specimens for the presence ketotic, it is essential for the child to and serum glucose measurement. of disease markers. Each state man- consume glucose to prevent protein Arterial blood gas measurement with dates a different newborn screening catabolism (Claudius et al., 2005). If calculation of anion gap can indicate panel for their population of new- the child is unable, intravenous ther- severity of metabolic acidosis. A writ- borns (Howell, 2009). Most states are apy can prevent complications associ- ten plan is advised for the family to now using the improved newborn ated with increased tyrosine levels. An have with them in the event of an screening test for TT1 that measures antiemetic may be ordered if nausea emergency. The written emergency succinylacetone (Morrissey, Sunny, and vomiting are present. Anti - plan can advise providers of treat- Fahim, Lubowski, & Caggana, 2011). emetics can also be prescribed as ment plans and how to contact med- Measurement of tyrosine is neither needed to prevent future episodes of ical genetics experts for consultation. specific nor sensitive for the identifi- ketosis and adverse outcomes The American College of Emergency cation of TT1 (Allard, Grenier, Korson, (Fedorowicz, Jagannath, & Carter, Physicians (ACEP) and the American & Zytkovicz, 2004). Succinylacetone 2011). Academy of Pediatrics (AAP) provide measurement by tandem mass spec- Without the steady consumption an online template that is useful in trometry is accurate and reliable for of fat and carbohydrates, muscle pro- developing this document (AAP, diagnosing TT1 in the newborn tein is metabolized and tyrosine levels 2010), which can be accessed online (Turgeon et al., 2008). Early identifica- rise. As tyrosine levels increase, toxic at http://www.aap.org/advocacy/blank tion of this life-threatening disease metabolites build up. One toxic form.pdf (ACEP, 2008). provides an opportunity to intervene metabolite is succinylacetone, which prior to symptom onset. causes ALAD porphyria in a complex Diet and Pharmacotherapy The clinical presentation is com- biochemical process that interferes plicated. Symptoms can be severe or with heme metabolism. This bio- TT1 is a treatable disease. An ex- chronic depending on phenotypic chemical interaction results in neuro- perienced team that includes a dieti- expression of the disease (Nakamura logic crisis (Anderson et al., 2005). cian, medical geneticist, advanced et al., 2007). Some children present practice nurse, psychologist, school with failure to thrive and poor growth, Neurologic Crisis nurse liaison, and other practitioners but others have an acute onset of will need to collaborate as an interdis- metabolic acidosis, hepa tomegaly, Neurologic crisis can present as a ciplinary team to enhance outcomes ascites, coagulopathy, and neurologic syndrome of severe pain, paralysis, (Paradis, 1996). The treatment in- crisis (Croffie, Gupta, Chong, & and respiratory arrest. Neurologic cludes a low-protein diet with med- Fitzgerald, 2010). Metabolic crisis is effects of FAH deficiency in TT1 ical food or formula, as well as the precipitated by hypoglycemia. include severe abdominal pain, ex- medication nitisinone (Orfadin®). The tremity pain, nausea, vomiting, weak- orphan drug nitisinone is used to ness, and altered level of conscious- treat TT1. Nitisinone shifts the meta-

62 PEDIATRIC NURSING/March-April 2014/Vol. 40/No. 2 Table 1. Age-Appropriate Care and Educational Needs of Children with TT1 and Families

Developmentally Appropriate Disease Management Timeline for Nursing Education of Caregivers and Patient Age of Patient *This is merely a guide that should be adjusted according to parent-child shared management preferences. 0 to 6 months • Caregivers learn to prepare prescribed formula using chemistry scale. • Caregivers learn to complete 24-hour diet history for review with dietician and medical geneticist. • Caregivers learn disease management and pathophysiology of protein metabolism in patient with TT1. • Caregivers learn of financial resources to purchase medical food (varies by state and insurance). • Caregivers learn importance of not showing signs of aversion to medical food since feeding is easily influenced by social situations. • Medical food is life-sustaining and must be a positive social experience to promote future healthy dietary habits. • Caregivers learn to schedule appointments with dietician every three months. • Caregivers learn to notify health care providers of episodes of ketosis (inability to consume calories can result in protein overdose when protein catabolism occurs). • Caregivers verbalize how protein catabolism can cause toxic metabolites to increase and become life- threatening. • Caregivers are given written emergency action plan to carry at all times to advise emergency providers of genetic provider contacts and emergency care of a child with TT1. • Caregivers learn to schedule yearly eye examinations to rule out tyrosine accumulation in corneas. • Caregivers administer Orfadin® as prescribed (Orfadin® must be refrigerated). 6 months • Caregivers introduce low-protein foods. • Caregivers learn to use books to look up protein content of all foods and enter on diet history record. • Caregivers learn to meet exact protein requirements (varies by weight and medical food prescription). • Caregivers learn to facilitate consumption of exact protein requirement. • Caregivers given low-protein cookbook, and introduced to online sources of low-protein foods and parent support groups. • Caregivers learn safe blood levels of tyrosine. • Caregivers learn to prevent ketosis. • Caregivers learn to measure ketones in urine and act appropriately to reverse ketosis with glucose solution or medical intervention as needed. 6 to 7 months • Caregivers introduce cup for low-protein formula as prescribed. 8 to 9 months • Caregivers introduce finger food within specific protein restriction. 10 to 15 months • Caregivers consider weaning to cup; continue medical food as prescribed by cup. • Caregivers learn to prepare low-protein meals. • Siblings may assist with low-protein diet preparation if interested. 2 to 3 years • Patient learns to distinguish acceptable foods. • Patient begins to learn to swallow capsule as tolerated. 4 to 5 years • Patient learns to count foods. • Patient begins to learn to weigh medical food and other low-protein foods on chemistry scales. • Begins to measure grams of medical food and assist with mixing of medical food. 5 to 6 years • Patient assists caregivers with formula preparation. • Caregivers teach child how to interact with other school-age children and satisfy their curiosity about specific dietary restrictions in a positive way. • Caregivers teach educators to monitor diet at school and prevent socially inappropriate behaviors that inhibit healthy diet habits. 7 to 10 years • Patient begins to list foods on 14-hour diet recall. • Patient learns to pack school lunch with parental assistance. • Patient chooses appropriate afterschool snacks. • Patient learns to look up protein grams and read labels of foods. • Patient learns to request restaurant menus with protein content when available. 10 to 12 years • Patient begins to prepare and consume medical food independently with parental monitoring. • Patient learns to prepare simple entrees with parental supervision. • Patient learns safe blood levels of tyrosine (below 500). • Patient learns to plot height and weight during clinic visits. • Patient learns why height and weight is important for overall health and development. • Patient attends yearly metabolic camp if available through referral in genetics clinic. (Children with TT1 usually can attend metabolic camp with children that have PKU since disease management is similar.)

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PEDIATRIC NURSING/March-April 2014/Vol. 40/No. 2 63 Tyrosinemia Type 1: An Overview of Nursing Care

Table 1. (continued) Age-Appropriate Care and Educational Needs of Children with TT1 and Families

Developmentally Appropriate Disease Management Timeline for Nursing Education of Caregivers and Patient Age of Patient *This is merely a guide that should be adjusted according to parent-child shared management preferences. 13 to 14 years • Patient learns menu planning. • Patient expands on preparation of meals with parental supervision. • Patient keeps calendar for blood draws. • Patient assumes responsibility for food records. • Patient assists with grocery shopping for appropriate low-protein foods. • Patient attends low protein cooking classes with peers with similar low-protein diet needs. • Patient learns to shop for low-protein foods online and in person if available. • Patient learns to interact with health care providers with autonomy. 15 to 17 years • Patient assumes responsibility for remembering recent lab results. • Patient schedules clinic appointments. • Patient schedules yearly eye exams to rule out tyrosine accumulation in corneas. 18 years • Patient transition to adult clinic care. • Patient manages diet and follow-up care. • Patient learns to access assistance when needed.

**If liver transplant is performed, diet therapy is no longer necessary. Sources: Kieckhefer & Trahms, 2000; Kieckhefer et al., 2009; Lewis-Gary, 2001.

bolic pathway for the catabolism of of a certified dietician who specializes itor signs of tubular injury with result- tyrosine (El-Karaksy et al., 2010). The in the management of children with ing Fanconi syndrome is prudent. recommended 1 to 2 mg/kg/day is inborn errors of metabolism. How- There is increased risk of renal carci- divided into two daily doses and ever, these foods are not always cov- noma related to toxic metabolites. should be titrated until succinylace- ered by health insurance plans (see Nitisinone can decrease progression tone is undetected in the urine (Al- Table 2). Chemistry scales for weigh- of renal disease (Santra, Preece, Dhalimy, Overturf, Finegold, & ing medical food and low-protein Hulton, & McKiernan, 2008). Mea - Grompe, 2002; D’Eufemia, Celli, Tetti, cookbooks are also available from surement of cystatin C is a better indi- & Finocchiaro, 2011; McKiernan, these companies. cator of renal function in the pedi- 2006). It must be taken at least one Corneal opacities have been atric population (Westhuyzen, 2006). hour before or two hours after a meal known to develop in some children Growth delays and vitamin D-resist- to promote complete absorption taking nitisinone for TT1. It is highly ant rickets related to renal disease are because food effect is unknown. It is recommended that plasma tyrosine common and usually improve with available in 2, 5, and 10 mg capsules. levels be measured frequently, and slit nitisinone therapy (Parri et al., 2006). For children unable to swallow cap- lamp ophthalmology examinations sules, the capsules can be opened and performed yearly (Ahmad, Teckman, Liver Transplant the contents suspended in a small & Lueder, 2002). Corneal opacities amount of water, formula, or apple have been associated with high plas- Decreased hepatocellular apopto- sauce immediately before use ma tyrosine levels; however, it is sis in the presence of toxic metabolites (“Nitisinone: New Drug...,” 2002). unclear if other factors may also con- in the liver increase the risk for hepato- One side effect of nitisinone tribute to this problem (Lock, Gaskin, cellular carcinoma (HCC) in children observed during clinical trials was Ellis, Provan, & Smith, 2006). To pre- with TT1. Consultation with a pedi- photophobia (eye irritation) related to vent this complication, tyrosine levels atric hepatologist and yearly ultra- elevated tyrosine levels. It is essential should be kept below 500 µM. sounds, CT scans with contrast, or that the child remain on a low pro- Yearly electrocardiograms to moni - gadolinium-enhanced MRI can detect tein diet while taking nitisinone to tor for interventricular septal hyper- hepatic nodules early (Lauenstein et prevent this complication (Kamboj, trophy and signs of cardiomyopathy al., 2007). Alpha-fetoprotein (AFP) lev- 2008; “Nitisinone: New Drug...,” 2002; are advised. This is a rare complica- els should be followed as well. Smith, 2008). Specific dietary recom- tion seen in some children with TT1. Elevations of AFP may indicate HCC. mendations are based on phenylala- If signs of cardiomyopathy are detect- Early referral for liver transplant before nine and tyrosine levels. The goal is to ed, referral to a pediatric cardiologist nodules are greater than 2 cm can be maintain serum phenylalanine above is advised. Children treated early with life-saving (Koelink et al., 2006). 20 to 30 µmole/L and serum tyrosine nitisinone are less likely to develop Unfortunately, even with early between 200 to 500 µM to prevent cardiomyopathy (Arora, Stumper, nitisinone treatment, some children corneal opacities and cognitive delays Wright, Kelly, & McKiernan, 2006). develop HCC and require liver trans- (Scott et al., 2008). Medical food and Tyrosine is also metabolized plant. After liver transplant, the new supplemental low-protein foods can within the kidneys. Consultation liver allograft provides FAH enzyme be ordered online with the assistance with a pediatric nephrologist to mon- to metabolize dietary tyrosine. Post-

64 PEDIATRIC NURSING/March-April 2014/Vol. 40/No. 2 Table 2. Medical Food and Formula Resource List

Company Name Contact Tyrosinemia Formula Low-Protein Foods Cambrooke Foods® 508.782.2300 Breads [email protected] Pasta http://Cambrookefoods.com Baking ingredient Ready Meals Cheese Rice Snacks Soups and seasonings

Mead Johnson™ 1.847.832.2420 Formula Per prescription and http://www.meadjohnson.com dietician management 1.812.429.5000

Abbott Nutrition 1.800.227.5767 Formula Per prescription and http://Abbottnutrition.com dietician management

Nutricia Advanced 1.800.365.7354 Baking mix Medical Nutrition Myspecialdiet.com Cereal LoProfin 1.877.636.2283 Crackers Pasta Cake mix Chips Rice Applied Nutrition http://medicalfood.com Snacks 1.800.605.0410 Candy 1.973.734.0023 Chips Baking mixes Cereal Dietary Specialties http://www.dietspec.com Egg replacer Breads Bagels Peanut butter spread Entrees Pizza Med Diet Lab 1.800.med.diet Soups 1.736.550.2020 Sauces http://www.med-diet.com Mixes Puddings Gels Bread

transplant, the low-protein diet is may slow nephropathy and decrease care and outpatient care settings. At unnecessary. The liver transplant the risk of renal carcinoma from different stages of disease progression, team and pediatric hepatologists exposure to FAA and succinylacetone treatment decisions will need to be manage maintenance of immunosup- in the kidneys. The kidneys also made that enhance both the quantity pression. Liver transplant is consid- metabolize tyrosine and may require and quality of life for the child and ered life-saving, but it is not a cure for transplant if end stage renal disease caregivers. The nurse assumes the role TT1. The risk of rejection, infection, develops (Jacobs et al., 2006). of patient advocate and educator to and malignancy after liver transplant assure that the family participates in is significant (Arnon et al., 2011; Nursing Care care planning and understands the Heffron et al., 2010). chronic nature of this lifelong condi- Liver transplant decreases the The care of the child and family tion. Anticipatory guidance on im- tyrosine load, but it does not abolish with TT1 requires an interdisciplinary, munizations, developmental mile- renal exposure to the fumarylacetoac- collaborative team approach. Follow- stones, and future therapy will etate (FAA). Low-dose nitisinone can ing the tenets of family-centered care, enhance the quality of life (Vinson, be used after liver transplant if suc- the family is considered an essential 2002). Prior to transplant, the pri- cinylacetone is found in the urine. It part of the team and should be mary treatment is prevention of is thought that low-dose nitisinone included in care planning in the acute metabolic deterioration and neuro-

PEDIATRIC NURSING/March-April 2014/Vol. 40/No. 2 65 Tyrosinemia Type 1: An Overview of Nursing Care

logic crisis with diet therapy and Acute exacerbations should be tivity to their struggle, education on nitisinone. These therapies should be managed in an acute care facility with technical care, and effective coping implemented in a developmentally close attention to glucose levels and strategies that lighten their burden. appropriate way (see Table 2) (Miller monitoring for metabolic acidosis Caring is truly the first step in assisting & MacDonald, 2006; Taylor, 1996). caused by a build up of toxic metabo- families dealing with the demands of lites during fasting. Parents should be managing a complicated disease such Growth and Development taught when to bring the patient to as TT1. Assessment of dietary intake by the hospital, when to consult the evaluation of a 24-hour food diary genetics team, and when to give while on a low-protein diet is an Pedialyte® or glucose solutions to References important nursing intervention. A avoid this type of metabolic crisis America Academy of Pediatrics (AAP). three-day dietary history can also pro- (2010). Policy statement – Emergency (Claudius et al., 2005). information forms and emergency pre- vide critical information about the Infection prevention is important. paredness for children with special dietary challenges families face. A Vaccine-preventable diseases can be health care needs. Pediatrics, 125(4), healthy diet within food restrictions avoided by routine vaccination to 829-837. will enhance normal growth and include yearly flu vaccines. After trans- American College of Emergency Physicians development. Growth measurements plant, no live virus vaccines can be (ACEP). (2008). Emergency information at routine visits should include height form for children with special needs. administered (Mack et al., 1996). Retrieved from http://www.acep. and weight measurements. Growth Teaching families simple infection con- org/content.aspx?id=26276 should be monitored by comparison trol, such as hand washing, can be help- Ahmad, S., Teckman, J.H., & Lueder, G.T. to children of comparable age and gen- ful when developmentally appropriate. (2002). Corneal opacities associated der with normalized values on stan- with NTBC treatment. American Journal dardized growth charts (Miller & Psychosocial Support of Ophthalmology, 134(2), 266-268. MacDonald, 2006). The complexity of disease manage- Al-Dhalimy, M., Overturf, K., Finegold, M., & Grompe, M. (2002). Long-term therapy Children and families managing ment and variety of complications with NTBC and tyrosine-restricted diet the strict diet will need detailed experienced by patients and their fam- in a murine model of hereditary instructions and feedback on progress ilies make psychosocial supportive care tyrosinemia type I. Molecular Genetics to be successful. An individualized and patient education essential. The and Metabolism, 75(1), 38-45. nutritional assessment by the metabol- psychosocial support of the family is a Allard, P., Grenier, A., Korson, M.S., & ic team will provide the dietary pre- critically important role for the nurse. Zytkovicz, T.H. (2004). Newborn screening for hepatorenal tyrosinemia by tan- scription, and nurses should educate The nurse’s role can minimize the dem mass spectrometry: Analysis of families about specific measures that impact of associated complications and succinylacetone extracted from dried improve compliance. Careful attention delay disease progression. Support of blood spots. Clinical Biochemistry, to delivery of medical food in a social- the family and child can facilitate 37(11), 1010-1015. ly and developmentally appropriate developmental achievement and allow Anderson, K., Bloomer, J., Bonkovsky, H., manner can make all the difference the patient to live a happy and produc- Kushner, J., Pierach, C., Pimstone, N., & Desnick, R. (2005). Recommenda- when compliance is an issue. The nurs- tive life. Green (2009). describes what it tions for the diagnosis and treatment of ing goal is for the child to eventually is like to manage a chronic disease that the acute porphyrias. Annals of Internal self-manage the disease (Kieckhefer & results in whole organ transplant. In an Medicine, 142(2), 439-450. Trahms, 2000; Kieckhefer, Trahms, ethnographic design, Green (2009) iso- Arnon, R., Annunziato, R., Miloh, T., Churchill, & Simpson, 2009). Co-man- lated four key themes identified by par- Wasserstein, M., Sogawa, H., Wilson, agement with family member supervi- ents of pediatric heart transplant recip- M., ... Kerkar, N. (2011). Liver transplantation for hereditary tyrosinemia type I: sion can be developed as early as two ients: coping with life, and constantly Analysis of the UNOS database. years of age and continue until the responsible, worried, and blessed. Pediatric Transplantation, 15(4), 400- patient is able to self-manage his or her Parents of these children are under 405. disease in adulthood. A table to outline immense psychological pressure, but Arora, N., Stumper, O., Wright, J., Kelly, D., & the care and educational needs of the often feel blessed by the gift of a second McKiernan, P. (2006). Cardiomyopathy family at each developmental stage chance at life for their child. in tyrosinaemia type I is common but usually benign. Journal of Inherited can be a useful tool when planning Coffey (2006) identified seven Metabolic Disease, 29(1), 54-57. individualized care (see Table 1). themes that describe how parents feel Ashorn, M., Pitkanen, S., Salo, M.K., & about parenting a child with a chronic Heikinheimo, M. (2006). Current strate- Patient and Family Education disease. This metasynthesis reveals the gies for the treatment of hereditary Early recognition and manage- complex emotions and hardship these tyrosinemia type I. Paediatric Drugs, ment of complications to minimize the families deal with on a daily basis. The 8(1), 47-54. Bailey, D.B., Jr., Skinner, D., & Warren, S.F. negative impact through appropriate seven themes revealed by this meta- (2005). Newborn screening for develop- care strategies will improve long-term synthesis described parental feelings mental disabilities: Reframing presump- outcomes. Minor viral illnesses can about survival as a family, the constant tive benefit. American Journal of Public become serious if calories are not con- worry and struggles, the burden of dis- Health, 95(11), 1889-1893. sumed. The catabolism of protein ease and an attempt to take charge, Bennett, M.J., & Rinaldo, P. (2001). The meta- stores can induce a metabolic crisis. It is critical periods during the illness, and bolic autopsy comes of age (Edi torial). Clinical Chemistry, 47(7), 1145-1146. important for families of children with bridges to the outside describing the Centers for Disease Control and Prevention TT1 to be advised of this danger. They isolation felt by some parents. (CDC). (2003). Contribution of selected should be instructed in how to test the Although parents often feel isolated metabolic diseases to early childhood urine for ketones. Ketones in the urine and anxious, the nurse’s role can pro- deaths – Virginia 1996-2001. Morbidity can alert families to the danger. vide critical emotional support, sensi- and Mortality Weekly Report, 52(29),

66 PEDIATRIC NURSING/March-April 2014/Vol. 40/No. 2 Instructions For Continuing Nursing Education

Contact Hours 677-679. Retrieved from http://www. Kieckhefer, G.M., & Trahms, C.M. (2000). cdc.gov/mmwr/preview/mmwrhtml/mm Supporting development of children with Tyrosinemia Type 1: 5229a1.htm chronic conditions: From compliance An Overview of Nursing Care Chace, D.H., DiPerna, J.C., Mitchell, B.L., toward shared management. Pediatric Sgroi, B., Hofman, L.F., & Naylor, E.W. Nursing, 26(4), 354-363. Deadline for Submission: (2001). Electroscopy tandem mass spec- Kieckhefer, G.M., Trahms, C.M., Churchill, April 30, 2016 trometry for analysis of acycarnitines in S.S., & Simpson, J.N. (2009). Measur ing dried postmortem blood specimens col- parent-child shared management of PED 1403 lected ay autopsy from infants with unex- chronic illness. Pediatric Nursing, 35(2), plained cause of death. Clinical 101-108. To Obtain CNE Contact Hours Chemistry, 47(7), 1166-1182. Koelink, C.J., van Hasselt, P., van der Ploeg, 1. For those wishing to obtain CNE contact Claudius, I., Fluharty, C., & Boles, R. (2005). A., van den Heuvel-Eibrink, M.M., hours, you must read the article and com- The emergency department approach to Wijburg, F.A., Bijleveld, C.M., & van plete the evaluation through Pediatric newborn and childhood metabolic crisis. Spronsen, F.J. (2006). Tyrosinemia type I Nursing’s Web site. Complete your eval- Emergency Medicine Clinics of North treated by NTBC: How does AFP predict America, 23(3), 843-883. liver cancer? Molecular Genetics and uation online and your CNE certificate Coffey, J.S. (2006). Parenting a child with Metabolism, 89(4), 310-315. will be mailed to you. Simply go to chronic illness: A metasynthesis. Pediatric Krous, H.F. (2010). Sudden unexpected death www.pediatricnursing.net/ce Nursing, 32(1), 51-59. in infancy and the dilemma of defining 2. Evaluations must be completed online Croffie, J., Gupta, S., Chong, S., & Fitzgerald, the sudden infant death syndrome. by the above deadline. Upon completion J. (2010). Tyrosinemia type 1 should be Current Pediatric Reviews, 6(1), 5-12. of the evaluation, a certificate for 1.3 suspected in infants with severe coagu- Larochelle, J., Mortezai, A., Belanger, M., contact hour(s) will be mailed. lopathy even in the absence of other Tremblay, M., Claveau, J.C., & Aubin, G. signs of liver failure. Pediatrics, 103(3), (1967). Experience with 37 infants with Fees – Subscriber: Free Regular: $20 675-768. tyrosinemia. Canadian Medical Asso - D’Eufemia, P., Celli, M., Tetti, M., & Finocchiaro, ciation Journal, 97(18), 1051-1054. R. (2011). Tyrosinemia type I: Long-term Lauenstein, T.C., Salman, K., Morreira, R., Goal outcome in a patient treated with doses of Heffron, T., Spivey, J.R., Martinez, E., ... The purpose of this learning activity is to NTBC lower than recommended. Martin, D.R. (2007). Gadolinium- enable the reader to discuss tyrosine mia European Journal of Pediatrics, 170(6), enhanced MRI for tumor surveillance type 1 (TT1), its pathophysiology, diag nosis, 819-819. before liver transplantation: Center- De Braekeleer, M., & Larochelle, J. (1990). based experience. American Journal of treatment, and implications for nursing. Genetic epidemiology of hereditary tyro- Roentgenology, 189(3), 663-670. sinemia in Quebec and in Saguenay-Lac- Lewis-Gary, M.D. (2001). Updates & kidbits. Objectives St-Jean. American Journal of Human Transitioning to adult health care facili- 1. Define tyrosinemia type 1 (TT1). Genetics, 47(2), 302-307. ties for young adults with a chronic con- El-Karaksy, H., Rashed, M., El-Sayed, R., El- dition. Pediatric Nursing, 27(5), 521-524. 2. Discuss the pathophysiology of TT1. Raziky, M., El-Koofy, N., El-Hawary, M., & Lock, E.A., Gaskin, P., Ellis, M., Provan, W.M., 3. Explain treatment options for TT1. Al-Dirbashi, O. (2010). Clinical practice. & Smith, L.L. (2006). Tyrosinemia pro- NTBC therapy for tyrosinemia type 1: duced by 2-(2-nitro-4-trifluoromethylben- 4. Discuss nursing implications when How much is enough? European Journal zoyl)-cyclohexane-1,3-dione (NTBC) in treating patients with TT1. of Pediatrics, 169(6), 689-693. doi:10. experimental animals and its relation- 1007/s00431-009-1090-1 ship to corneal injury. Toxicology and Fedorowicz, Z., Jagannath, V.A., & Carter, B. Applied Pharmacology, 215(1), 9-16. Statement of Disclosure: The author(s) report - (2011). Antiemetics for reducing vomiting Mack, D.R., Chartrand, S.A., Ruby, E.I., ed no actual or potential conflict of interest in related to acute gastroenteritis in children Antonson, D.L., Shaw, B.W., Jr., & relation to this continuing nursing education act - and adolescents. Cochrane Data base of Heffron, T.G. (1996). Influenza vaccina- ivity. Systematic Reviews, 7(9). doi:10.1002/ tion following liver transplantation in chil- The Pediatric Nursing Editorial Board members 14651858.CD005506.pub5 dren. Liver Transplantation and Surgery, reported no actual or potential conflict of inter- Green, N., Baily, M. A., Murray, T. H., Moyer, V., 2(6), 431-437. est in relation to this continuing nursing educa- Teutsch, S. M., & Botkin, J. R. (2009). McHugh, D.M.S., Cameron, C.A., Abdenur, tion activity. Every child is priceless: Deba ting effec- J.E., Abdulrahman, M., Adair, O., Al tive newborn screening policy. Hastings Nuaimi, S.A., ... Zakowicz, W.M. (2011). Center Report, 39(1), 6-8. Clinical validation of cutoff target ranges in This independent study activity is provided Heffron, T.G., Pillen, T., Smallwood, G., Henry, newborn screening of metabolic disorders by Anthony J. Jannetti, Inc. (AJJ). S., Sekar, S., Solis, D., … Romero, R. by tandem mass spectrometry: A world- (2010). Liver retransplantation in children: wide collaborative project. Genetics in Anthony J. Jannetti, Inc. is accredited as a The Atlanta experience. Pediatric Medicine, 13(3), 230-254. provider of continuing nursing education by the Transplantation, 14(3), 417-425. McKiernan, P.J. (2006). Nitisinone in the treat- American Nurses Credentialing Center's Com- Howell, R.R. (2009). Every child is priceless: ment of hereditary Trosinemia type 1. mission on Accreditation. Debating effective newborn screening Drugs, 66(6), 743-750. Anthony J. Jannetti, Inc. is a provider policy. The Hastings Center Report, Miller, D., & MacDonald, D. (2006). Manage - approved by the California Board of Registered 39(1), 4-6. ment of pediatric patients with chronic kid- Nursing, Provider Number, CEP 5387. Hunt, C.E., & Hauck, F.R. (2006). Sudden infant ney disease. Pediatric Nursing, 32(2), Licenses in the state of California must death syndrome. Canadian Medical 128-135. retain this certificate for four years after the CNE Association Journal, 174(13), 1861-1869. Mitchell, G., Larochelle, J., Lambert, M., activity is completed. Jacobs, S.M., van Beurden, D.H., Klomp, Michaud, J., Grenier, A., Ogier, H., ... This article was reviewed and formatted for L.W., Berger, R., & van den Berg, I.E. Larbisseau, A. (1990). Neurologic crises in contact hour credit by Rosemarie Marmion, (2006). Kidneys of mice with hereditary hereditary tyrosinemia. The New England MSN, RN-BC, NE-BC, Anthony J. Jannetti, Inc., tyrosinemia type I are extremely sensi- Journal of Medicine, 322(7), 432-437. Education Director; and Judy A. Rollins, PhD, tive to cytotoxicity. Pediatric Research, Morrissey, M.A., Sunny, S., Fahim, A., RN, Pediatric Nursing Editor. 59(3), 365-370. Lubowski, C., & Caggana, M. (2011). Kamboj, M. (2008). Clinical approach to the Newborn screening for Tyr-I: Two years’ diagnoses of inborn errors of metabo- experience of the New York State pro- lism. Pediatric Clinics of North America, gram. Molecular Genetics and Meta- 55(5), 1113-1127. bolism, 103(2), 191-192.

PEDIATRIC NURSING/March-April 2014/Vol. 40/No. 2 67 Tyrosinemia Type 1: An Overview of Nursing Care

Nakamura, K., Tanaka, Y., Mitsubuchi, H., & zebras? A case report. Dimensions of Schunemann, J., Oxman, A., Brozek, J., Endo, F. (2007). Animal models of Critical Care Nursing, 25(3), 103-109. Glasziou, P., Jaeschke, R., Vist, G., ... tyrosinemia. The Journal of Nutrition, Paradis, K. (1996). Tyrosinemia: The Quebec Guyatt, G.H. (2008). GRADE: Grading 137(6, Suppl. 1), 1556S-1560S. experience. Clinical and Investigative quality of evidence and strength of rec- “Nitisinone: New drug. Type 1 tyrosinemia. An Medicine, 19(5), 311-316. ommendations for diagnostic tests and effective drug.” (2007). Prescrire Inter- Parri, N., Indolfi, G., Poggi, G., Donati, M.A., strategies. British Medical Journal, 336, national, 16(88), 56-58. Gasperini, S., Procopio, E., & Resti, M. 1106-1110. Nobili, V., Jenkner, A., Francalanci, P., (2006). Liver disease and hypophos- Scott, C.R. (2006). The genetic tyrosinemias. Castellano, A., Holme, E., Callea, F., & phatemic rickets: Suspect tyrosinemia American Journal of Medical Genetics Dionisi-Vici, C. (2010). Tyrosinemia type TYPE-1. Digestive and Liver Disease, Part C (Seminars in Medical Genetics), 1: Metastatic hepatoblastoma with a 38(10), A112-A113. 142C(2), 121-126. favorable outcome. Pediatrics, 126(1), Rocha, M.E., Bandy, B., Costa, C.A., de Scott, C.R., King, L.S., & Trahms, C. (2008). e235-e238. Barros, M.P., Pinto, A.M., & Bechara, Tyrosinemia type 1. Gene Reviews. Nyhan, W.L., Barshop, B.A., & Ozand, P.T. E.J. (2000). Iron mobilization by succiny- Retrieved from http://www.ncbi.nlm.nih. (2005). Atlas of metabolic diseases. lacetone methyl ester in rats. A model gov/books/NBK1515/ New York, NY: Oxford University Press. study for hereditary tyrosinemia and por- Smith, M. (2008). Care of the infant with inher- Orejuela, D., Jorquera, R., Bergeron, A., phyrias characterized by 5-aminolevulin- ent metabolic disease. Paediatric Finegold, M.J., & Tanguay, R.M. (2008). ic acid overload. Free Radical Research, Nursing, 20(4), 38-44. Hepatic stress in hereditary tyrosinemia 32(4), 343-353. Taylor, J.H. (1996). End stage renal disease in type 1 (HT1) activates the AKT survival Santra, S., Preece, M., Hulton, S.A., & children: Diagnosis, management, and pathway in the fah-/- knockout mice McKiernan, P. (2008). Renal tubular func- interventions. Pediatric Nursing, 22(6), model. Journal of Hepatology, 48(2), tion in children with tyrosinaemia type I 481-490. 308-317. treated with nitisinone. Journal of Palmer, K.M. (2006). Abdominal pain due to Inherited Metabolic Disease, 31(3), 399- continued on page 90 acute intermittent porphyria: When is the 402. sound of hoof-beats not horses, but Pediatric Nursing Guidelines for Authors

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68 PEDIATRIC NURSING/March-April 2014/Vol. 40/No. 2 Tyrosinemia Type 1 Additional Readings Eggenhofer, E., Doenecke, A., Renner, P., continued from page 68 Slowik, P., Piso, P., Geissler, E.K., ... Popp, F.C. (2010). High volume naked Turgeon, C., Magera, M.J., Allard, P., Tortorelli, DNA tail-vein injection restores liver func- S., Gavrilov, D., Oglesbee, D., ... Matern, tion in Fah-knock out mice. Journal of D. (2008). Combined newborn screening Gastroenterology and Hepatology, 25(5), for succinylacetone, amino acids, and 1002-1008. acylcarnitines in dried blood spots. Heffron, C. (2005). A perfect fit: Blending the Clinical Chemistry, 54(4), 657-664. roles of teacher and nurse. Association of Vinson, J.A. (2002). Practice applications of Women’s Health, Obstetric, and Neonatal research. Children with asthma: Initial Nurses Lifelines, 9(3), 272, 271. development of the Child Resilience Paulk, N.K., Wursthorn, K., Wang, Z., Finegold, Model. Pediatric Nursing, 28(2), 149-158. M.J., Kay, M.A., & Grompe, M. (2010). Westhuyzen, J. (2006). Cystatin C: A promis- Adeno-associated virus gene repair cor- ing marker and predictor of impaired rects a mouse model of hereditary renal function. Annals of Clinical and tyrosinemia in vivo. Hepatology, 51(4), Laboratory Science, 36(4), 387-394. 1200-1208. Wyllie, R., & Hyams, J.S. (2006). Pediatric gas- Rasko, J.E.J. (2010). A gene therapy renais- trointestinal and liver disease patho - sance? Journal of Gastroenterology and physiology/diagnosis/management. Hepatology, 25(5), 848-850. Philadelphia: Saunders Elsevier.

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