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GALT Defi ciency Abstract alactosemia is an autosomal recessive Galactosemia is an inborn error of that results from a genetic condition caused by a defect in deficiency in one of three , uridine diphosphate galactose 4’epimerase, the Leloir pathway resulting in defi - , or galactose-1-phosphate uridyltransferase (GALT). This article G ciency of one of three enzymes, uridine focuses on classical, clinical variant, and biochemical variant (Duarte) galac- diphosphate galactose 4’epimerase (GALE), tosemias caused by GALT deficiency. A brief overview of galactosemia galactokinase (GALK), or galactose-1-phosphate and is presented, followed by detailed information about (Gal-1-P) uridyltransferase (GALT). Although each of the conditions. Confirmatory testing, acute and long-term manage- the mechanism for galactosemia is not fully ment, and outcome for these galactosemia types are discussed as well as the understood, changes in the GALT gene reduce importance of genetic counseling and testing for the infant and family to refine GALT enzyme that prevents conversion of Gal- reproductive risk. 1-P to -1-phosphate. As such, Gal-1-P Key words Classic; Galactosemia; Galactose-1-phosphate uridyltransferase defi - ciency disease; Galactose-1-phosphate uridylyltransferase; GALT defi ciency. Sharon Anderson, DNP, NNP-BC, APNG

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Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. accumulates in cells and galactose is converted to galacti- tol or oxidized to galactonate. Accumulation of these Galactosemia is an inborn error of galactose substances in blood and tissue triggers symptoms ( Varela-Lema et al., 2016). The biochemical and clinical metabolism caused by a genetic change that variability between GALT defi ciency types depends on residual enzyme activity. results in defi ciency of one of three enzymes, Because classic GALE and GALK defi ciency galactose- uridine diphosphate galactose 4’epimerase mias are rare, this review provides nurses, practitioners, and midwives with information about three more fre- (GALE), galactokinase (GALK), or galactose- quently encountered GALT defi ciency . 1-phosphate uridyltransferase (GALT). Newborn screening, diagnostic process, presenting symp- toms, initial and ongoing management, and associated outcomes are covered. Importance and rationale for ge- netic testing as part of the diagnostic process is discussed Homozygosity or compound heterozygosity for CG mu- and nursing implications are summarized. tations will cause severe disease. Overall incidence of CG varies based on race and ethnicity. It is highest among Newborn Screening for Galactosemia Caucasians ranging from approximately 1 in 16,000 to 1 Newborn screening for galactosemia may identify all in 44,000 infants in the United Kingdom and Ireland galactosemia types; however, the primary target is (Coss et al., 2013). Across the United States and world- GALT defi ciency galactosemia identifi ed by a combina- wide, prevalence ranges between 1 in 30,000 and 1 in tion of total galactose, GALT enzyme and for select pro- 60,000 infants (Fridovich-Keil & Walter, 2008). The grams, mutation screening. A signifi cantly reduced most prevalent CG mutation is Q188R, accounting for GALT enzyme and elevated total galactose level suggest 60% to 70% of alleles, followed by K285N that accounts classical (CG) and sometimes, classical variant galacto- for 25% to 40% of alleles among individuals from south- semia (VG), whereas more subtle changes suggest Du- ern Germany, Austria, and Croatia (Mayo Clinic, n.d.). arte galactosemia (DG) (Table 1). Some states offer a common galactosemia gene panel refl ex test to refi ne the Presenting Symptoms diagnosis. Since implementation of newborn screening, fewer infants Even with screening, an infant with galactosemia may with CG present with overwhelming illness and life- be missed. Blood transfusion or infants receiving a low threatening symptoms (Berry, 2012). However, deaths galactose-containing formula at screening may elicit a false- have been reported as early as 8 days of age (Berry, 2014) negative result. Careful review of the test result, patient and those who survive and continue to ingest galactose- history, and feeding at the time of testing ensures accurate containing formulas and foods will suffer severe brain interpretation. Most importantly, even when newborn damage (Otaduy et al., 2006). Subtle symptoms include screening results are normal, infants who present with lethargy, hypotonia, poor feeding, , diarrhea, and symptoms suggestive of galactosemia should be tested. prolonged jaundice. may or may not be present. With ongoing galactose exposure, hepatocellular damage, Classical Galactosemia bleeding diathesis, cerebral edema, Escherichia coli The GALT gene has more than 300 mutations (ARUP (E. coli) sepsis, and hyperchloremic acidosis with amino- Laboratories, n.d.). It is located on chromosome 9p13. aciduria may develop. If left untreated, encephalopathy, shock, and death may occur (Berry, 2014; Broomfi eld, Table 1. Newborn Screening Total Galactose and Brain, & Gruenwald, 2011; Varela-Lema et al., 2016). GALT Enzyme Levels in GALT Defi ciency Galactosemia Diagnostic Testing Galactosemia Total GALT Enzyme Confi rmatory testing for CG includes GALT enzyme and/ Type Galactose (activity level) or mutation analysis (Welling et al., 2017). Galactose- Classical ↑↑↑ ↓↓↓ (<1%) 1-phosphate, RBC, free galactose, and urine Clinical variant ↑↑ ↓↓–↓↓↓ (1%–10%) may be part of the diagnostic evaluation and ongoing sur- veillance (Table 2). Although a biochemical diagnosis can Biochemical Normal to ↑↓ (15%–33%) variant (Duarte) be made based on enzyme activity and biochemical me- tabolites, if GALT enzyme is <50% and genetic testing has These values refl ect levels for newborns fed breast or cow's not been performed, it should be offered. The common milk-based formula who have not received blood transfusion. mutation panel has a detection frequency of almost 88% Soy-based formula feedings will result in lower total galactose levels than those receiving galactose feedings. The enzyme (Berry, 2014) but if mutations are not identifi ed, gene se- level, however, will not be affected by dietary galactose intake. quencing and deletion/duplication testing are available. Total galactose and GALT levels may be low in infants who have received a blood transfusion because it may refl ect the Initial Treatment galactosemia status of the donor, rather than the newborn. Whether symptomatic or asymptomatic, treatment for GALT = galactose-1-phosphate uridyltransferase CG is immediate and begins by removing exogenous

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Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Table 2. Diagnostic and Surveillance Testing for Classical and Clinical Variant Galactosemias Test Normal Galactosemia Galactose-1-phosphate ≥24.5 nmol/h/mg Hgb Classical: <1% activity uridyltransferase Clinical variant: 1%–10% activity Galactose-1-phosphate, <1 mg/dL >10 mg/dL (as high as 120 mg/dL) RBC On treatment: <5 mg/dL Plasma-free galactose 5–20 mmol/L >10 mg/dL (as high as 90–360 mg/dL) Urine galactitol Values vary based on age: Elevations vary (age-specifi c normals) Infants: <109 mmol/mol creatinine On treatment: <78 mmol/mol creatinine Adults: <13 mmol/mol creatinine sources of dietary galactose to prevent galactose expo- are replaced with galactose-free/low-galactose substitu- sure and accumulation. After discontinuing breast and tions. There are food lists, on-line and published cow's milk-based formula, symptomatic newborns may resources, and parent and peer support groups to help require intravenous hydration, phototherapy, and/or ex- parents, care providers, and eventually patients monitor change transfusion. Vitamin K and fresh frozen plasma galactose intake. are used to treat bleeding concerns resulting from hepatic When over-the-counter or prescription medications are injury. Other treatments may include bicarbonate for aci- required, galactose content must be checked. Generally, dosis and antibiotics for disease-associated E. coli sepsis liquid medications do not contain galactose but tablet (Berry, 2012). Once stabilized, feedings of galactose-free medications often do. When an alternate galactose-free formula can be provided (Table 3). drug is available, it should be substituted. If not, the ben- efi ts and limitations of a short-term course of galactose- Lifelong Management containing medication must be weighed. During early infancy, diet is formula-based and easy to man- With strict dietary control, Gal-1-P, RBC should re- age. To minimize exposure to small amounts of galactose in main <5 mg/dL and urine galactitol <78 mmol/mol cre- premixed formulas, powdered formula is recommended. atinine (Berry, 2014). After diagnosis, ongoing metabolic Breastfeeding mothers require guidance and support to genetic visits are recommended every 3 months for the wean breast milk production. Infants receiving services fi rst year, every 6 months for 1 year, and then annually. through the Special Supplemental Nutrition Program Visits include diet analysis, nutritional counseling with a for Women, Infants, and Children (WIC) may require metabolic dietitian, and assessment of metabolic control, documentation to change formula and over time, supply growth, and coordination of care based on disease- condition-appropriate nutritious foods in lieu of milk and associated risks and complications. cheese. As the diet advances, treatment rests with dietary ga- Complications restriction guided by a metabolic dietitian. Milk, Although the exact mechanism remains unclear, there milk products, and casein- and whey-containing foods are long-term complications associated with pre- and postnatal exogenous and endogenous galactose expo- Table 3. Acceptable Formulas for Use in GALT sure and even, strict galactose restriction. Intellectual Defi ciency Galactosemia impairment, verbal dyspraxia, and neurological impair- ment may be linked to cerebral white matter changes. Soy-Based Formulas* Other complications include cataracts, , Similac® Soy Isomil® growth delay, and hypergonadotropic hypogonadism in Enfamil™ ProSobee™ females. Gerber® Good Start® Soy Intellectual impairment. Mean IQ is reduced in chil- dren with CG (70–90) especially among those with the Hypoallergenic/Elemental Formulas Q188R mutation (Broomfi eld et al., 2011). It has been Enfamil™ Pregestimil™ hypothesized intellectual abilities decline over time, but Similac® Alimentum® this has not been supported in the literature. Develop- Enfamil™ Nutramigen™ mental assessments are recommended at age 1 and then Nutricia Neocate® every 1 to 3 years (Berry, 2014). Early intervention and GALT = galactose-1-phosphate uridyltransferase individualized education plans are important in meeting *Generic soy formulas are comparable. Because they may vary, developmental, intellectual, and learning needs. it is recommended providers check with the manufacturer. Speech and language defi cits. Speech diffi culties are Notes. 1) Enfamil™ Lactose Free formula contains cow's milk common and include delayed vocabulary, articulation as the protein source and is not galactose-free. 2) It is recom- problems and, less frequently, verbal dyspraxia. Speech mended infants with classical and clinical variant galactose- and language screening performed alone or in combina- mia receive powdered (not concentrate or premixed) formula. tion with cognitive screening should take place at 7 to 12

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Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Treatment for classical and clinical variant galactosemia rests with lifelong dietary galactose restriction, whereas treatment for is more controversial. Africa Studio / shutterstock months and ages 2, 3, and 5 years (Welling et al., 2017). should be consulted to address atypical When indicated, speech is intensive and, unfortu- growth concerns. nately, a large percentage of individuals are refractory Hypergonadotropic hypogonadism. Primary ovarian (Berry, 2014). insuffi ciency (POI) and premature menopause are symp- Neurological problems. Speech and coordination dis- toms of hypergonadotropic hypogonadism experienced orders frequently cooccur. Despite strict dietary galactose by women with CG. Although believed to be a result of restriction, over time, 10% to 20% develop extrapyrami- chronic Gal-1-P and galactitol exposure, the mechanism dal symptoms including severe, progressive , fi ne- remains unknown. Estradiol, follicle stimulating, and motor tremors, , and dystonia (Rubio-Agusti luteinizing hormone levels should be assessed at age 1 et al., 2013; Waisbren et al., 2012; Welling et al., 2017). and 2 years and puberty. Typically, females present with Clinical screening should begin at 2 to 3 years (Welling pubertal delay and primary or secondary et al.) and consultation and physical and oc- progressing to POI. As they approach puberty, girls cupational may be warranted. should be carefully monitored by a pediatric endocri- Cataracts. Accumulation of galactitol is thought to be nologist and estrogen and progestin support provided as the cause for cataracts (Broomfi eld et al., 2011). Cata- needed (Broomfi eld et al., 2011; Mayatepek et al., 2010). racts were originally reported in up to 30% of patients The risk for POI does not directly correlate with strict with CG but more recent evidence suggests the rate is dietary galactose restriction, which suggests ovarian tox- closer to 14% (Broomfi eld et al.). Most cataracts resolve icity may occur early in life. Although approximately with dietary galactose restriction and newborns should 80% of women develop ovarian dysfunction, spontane- receive follow-up until resolved (Welling ous pregnancy can occur (Broomfi eld et al.). Birth et al., 2017). After baseline, slit lamp examination is rec- control should be offered to women not wishing to con- ommended at ages 1, 5, and during adolescence (Berry, ceive and reproductive options should be discussed with 2014) and for all patients who do not comply with women with POI. dietary galactose restriction (Welling et al.). Osteopenia and osteoporosis. Strict restriction of milk Patient Outcome and milk products places individuals at increased risk for The rationale for screening newborns for galactosemia is osteopenia and premature osteoporosis. Calcium, phos- to identify at-risk newborns and minimize galactose toxic- phorus, and 25-hydroxyvitamin D levels are recommend- ity and associated morbidity and mortality. There is no ed annually. Optimized dietary calcium intake and question, galactose restriction for newborns with CG is vitamin D3 and calcium supplementation, laboratory life-saving. Several researchers, however, have examined testing, and regular exercise are recommended (Welling presymptomatic treatment and failed to demonstrate bet- et al., 2017). Bone mineral density scanning is recom- ter long-term outcome for those treated earlier rather than mended annually beginning at school age (Berry, 2014; later. Antenatal maternal dietary galactose restriction does Mayatepek, Hoffmann, & Meissner, 2010) and every not improve patient outcome and in some cases, resulted 5 years after puberty is complete (Welling et al.). in poorer outcomes (Hughes et al., 2009). Although not Growth delay. Growth is generally delayed in child- yet well studied, several researchers hypothesize strict hood and early adolescence and those with higher residu- dietary galactose restriction may contribute to long-term al enzyme levels have improved adult height (Berry, systemic problems and a more liberal intake of galactose 2014). Although some women may fall short of calculat- may improve outcomes (Coman et al., 2010; Hughes ed midparental height (Panis, Gerver, & Rubio-Gozalbo, et al.). The long-term effect of this remains unknown and 2007), most will reach normal height-for-age. Careful therefore, treatment for CG remains lifelong dietary galac- monitoring of growth is recommended through puberty. tose restriction, surveillance, and anticipatory guidance.

January/February 2018 MCN 47

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Table 4. Risk to Have a Child with Galactosemia Based on Parent Carrier Status: Exemplars Classical/Classical Variant Galactosemia Carrier (NG) Parents Parent 1 Unless one of the parents has classical or classical variant galactosemia, each parent is NGan obligate carrier for galactosemia. As such, the recurrence risk to have a child with clas- sical galactosemia (GG) with each pregnancy is 1 in 4 (25%). There is a 50% risk with each NNNNGpregnancy to have a child who is a carrier for galactosemia (NG) and 25% chance to have a child with two normal alleles (NN). Parent 2 GNGGG Classical/Classical Variant Galactosemia Carrier (NG) and Biochemical Variant (Duarte) Galactosemia Carrier (ND) Parents Parent 1 This diagram shows the risk for two parents, one a carrier for the classical galactosemia gene (Parent 1) and the other, the Duarte variant (Parent 2). In this case, the recurrence NG risk to have a child with Duarte galactosemia (DG) with each pregnancy is 1 in 4 (25%). NNNNGThere is a 25% risk with each pregnancy to have a child who is a carrier for classical ga- lactosemia (NG), 25% risk to have a child who is a carrier for the Duarte variant (ND), and

Parent 2 DNDDG 25% chance to have a child with two normal alleles (NN). Classical/Classical Variant Galactosemia Carrier (NG) and Biochemical Variant (Duarte) Galactosemia (DG) Parents Parent 1 In the unlikely event, one parent (Parent 1) has Duarte galactosemia (DG), the recurrence risk to have a child with classical galactosemia (GG) will depend on the carrier status of DG the other parent. In this diagram, if Parent 2 is a carrier for classical galactosemia, there is NNDNGa 25% risk with each pregnancy to have a child with Duarte galactosemia (DG) but there is also a 25% risk to have a child with classical galactosemia (GG).

Parent 2 GDGGG

N = normal allele; D = Duarte allele; G = classical galactosemia allele; GG = classical/variant galactosemia; DG = Duarte galacto- semia, NG = carrier for classical/variant galactosemia; ND = carrier for Duarte gene Note. Newborns homozygous for the Duarte gene (DD) may also be identifi ed through newborn screening. Typically, these infants have approximately 50% GALT enzyme activity and do not require treatment or follow-up.

Clinical Variant Galactosemia CG and VG, GALT enzyme levels are higher, ranging be- Clinical VG caused by homozygosity of S135L occurs tween 15% and 33% (Berry, 2014). Although Gal-1-P, primarily among African Americans and native Africans RBC, and urine galactitol galactose metabolites are elevat- in South Africa. Newborns with VG present with barely ed during infancy, most normalize by age 2. There is con- detectable or absent (0%–10%) GALT activity. Different troversy about the short- and long-term signifi cance and from CG, individuals with VG have higher enzyme levels treatment of this milder galactosemia type. Most patients in the brain and intestines. are lost-to-follow-up and thus, there are sparse long-term A portion of infants with VG will have Gal-1-P, RBC data to support any one approach to care. As a result, levels similar to newborns with CG and thus, manifest there are varying opinions regarding whether DG is a “real early clinical symptoms such as growth failure, disease” (Berry) and what, if any, treatment is required. disease, and cataracts (Berry, 2014). For the majority, he- patic enzyme levels as high as 10% make hypergalactose- Treatment Controversy mia less severe than with CG. As such, timely treatment Several studies have compared infants and children with minimizes risk for E. coli sepsis and chronic, long-term DG treated with strict galactose restriction to those who complications such as intellectual disability, speech prob- were not with mixed results. One frequently cited study lems, and POI (Berry). Treatment recommendations are by Ficicioglu et al. (2008) compared a cohort of children similar to CG and based on the severity of enzyme defi - with DG ages 1 to 6 years (n = 28). One group received ciency. Overall, the prognosis for VG is good. strict dietary restriction with periodic assessment of ga- lactose metabolites (n = 17) the fi rst year of life, whereas the other received no restriction (n = 11). No signifi cant Biochemical Variant (Duarte) differences in clinical or long-term outcomes between the Galactosemia two groups were revealed. Similarly, Powell et al. (2009) A milder variant of galactosemia, DG, results when an in- examined a patient cohort of 59 children with DG and dividual is compound heterozygous for a classical (e.g., found no increased rates of intellectual disability, cere- Q188R) and Duarte (N314D) change in the GALT gene. bral palsy, autism spectrum disorder, hearing or vision Duarte galactosemia affects approximately 1 in every impairment. There were, however, higher rates of special 4,000 newborns and is far more common than either CG education (primarily speech and language disorders) and VG combined (Ficicioglu et al., 2008). In contrast to among children with DG.

48 volume 43 | number 1 January/February 2018

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. The risk for potential long-term ovarian dysfunction follow-up for the fi rst 1 to 2 years of life. To balance these was studied by Sanders et al. (2009). Anti-müllerian and divergent approaches, some have opted to alternate breast follicle-stimulating hormones were obtained in girls with with soy-based formula feedings for mothers who want DG and compared with controls. Values were indistin- to breastfeed. Although there is no one standard approach guishable between the groups. This suggests females with to DG at this time, a group of international experts re- DG are not at risk for POI and as such, endocrine evalu- cently published treatment guidelines recommending ation is not recommended (Welling et al., 2017). these patients not be treated (Welling et al., 2017).

Treatment Genetic Counseling The lack of consensus regarding treatment makes it diffi - Regardless of the type and severity, genetic counseling cult to recommend any one approach. Clinical manage- should be provided to families of a newborn diagnosed ment may range from strict dietary galactose restriction with galactosemia. Because it is an autosomal recessive with ongoing biochemical and developmental surveil- condition, at a minimum, both parents are obligate lance to no dietary restriction or testing with annual carriers for galactosemia and the recurrence risk for Table 5. Nursing Implications and Considerations During Diagnostic Process Perform baseline infant assessment to determine if emergency care is needed. If symptomatic refer to the emergency department. Provide parents with general education about newborn screening. Provide parents with specifi c education about newborn screening for galactosemia (Table 6). Discontinue galactose-containing feedings and provide information about galactose-free, powdered formula options. Explain to parents the infant is being treated as long as he/she is receiving galactose-free formula. Provide breastfeeding mothers with information regarding how to express and safely store breast milk during diagnostic process. Refer to metabolic genetic center for confi rmatory testing. Classical Galactosemia Ensure maintenance of galactose-restricted diet and ongoing follow-up with a metabolic center, dietitian, and biochemi- cal monitoring. Minimize exposure to medications that contain galactose. Assist mother who is expressing breast milk to wean. Monitor for potential disease complications, facilitate surveillance, and make timely referrals when needed including: Development/Cognition. Speech. Coordination disorders. Vision (cataracts). Osteopenia/Osteoporosis (calcium and vitamin D3 intake). Growth (height). Puberty. Premature ovarian insuffi ciency (pregnancy/fertility). Other considerations: Assist with WIC paperwork based on dietary restriction. Refer diet questions (especially when solid foods are introduced) to the metabolic dietitian who will teach the par- ents what foods to avoid and how to read labels. Assist with day care/school dietary considerations. Facilitate referral to Early Intervention Program. Ensure assessment and ongoing involvement with Child Study Team and Individualized Education and 504 Plans. Variant Galactosemia Assess maintenance of galactose-restricted diet and ongoing monitoring by a metabolic center and dietitian. Assist mother who is expressing breast milk to wean. Monitor for potential disease complications, facilitate surveillance, and make timely referrals when needed. If enzyme activity is extremely low, follow recommendations outlined under classical galactosemia. Duarte Galactosemia Collaborate with metabolic team and follow/reinforce established treatment plan because there may be different care approaches depending on the patient, provider, and parents.

January/February 2018 MCN 49

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Table 6. Newborn Screening and Galactosemia Provider and Parent Information, Resources, and Support Provider Web site ACMG Newborn Screening ACT Sheets and https://www.ncbi.nlm.nih.gov/books/NBK55827/ Confi rmatory Algorithms Provider and Parent Baby’s First Test: https://www.babysfi rsttest.org/newborn-screening/conditions/ Classical Galactosemia classic-galactosemia#about Genetic Home Reference: https://ghr.nlm.nih.gov/condition/galactosemia#diagnosis Galactosemia National Organization for Rare Disorders: https://rarediseases.org/rare-diseases/galactosemia/ Galactosemia Genetic and Rare Diseases Information Center: https://rarediseases.info.nih.gov/diseases/2424/galactosemia Galactosemia Genetic and Rare Diseases Information Center: https://rarediseases.info.nih.gov/diseases/12908/duarte- Duarte Galactosemia galactosemia Parent Galactosaemia Support Group www.galactosaemia.org/ Galactosemia Foundation www.galactosemia.org/

ACMG = American College of Medical and Genomics parents to have another child with galactosemia is at restriction, lifelong galactose restriction and long-term least 25%. Inheritance patterns and options for paren- follow-up remain standard of care for CG and VG, tal genetic testing to refi ne recurrence risks for future whereas restriction for DG remains controversial. Ge- pregnancies should be discussed (Table 4). Identifying netic counseling to review genetic testing options to pro- GALT mutations for the patient and carrier screening vide prognosis, guide treatment, and refi ne recurrence for parents and other family members should be of- risk for future pregnancies should be offered. fered. Preimplantation genetic diagnosis and prenatal diagnosis by chorionic villus sampling or amniocentesis Sharon Anderson is an Assistant Professor, Rutgers School should be discussed with interested parents, especially of Nursing, Newark, and Advanced Practice Nurse, Pedi- those at risk to have a child with CG. In the absence of atric Genetics, Rutgers Robert Wood Johnson Medical prenatal diagnosis, conservative treatment includes soy School, New Brunswick, NJ. The author can be reached formula feedings until newborn screening and diagnos- via e-mail at [email protected] tic testing can be performed. Mothers committed to breastfeeding should be provided with instructions The author declares no confl icts of interest. regarding how to safely express and store breast milk until test results are available. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Nursing Implications Care for a newborn with a suspected or confi rmed diag- DOI:10.1097/NMC.0000000000000388 nosis of GALT defi ciency galactosemia can be complex. Nurses at all practice levels must have a basic understand- References ing of newborn screening and galactosemia to provide ARUP Laboratories. (n.d.). The University of Utah Department of , GALT Database. Retrieved from www.arup.utah.edu/ information and support to families. Based on the specifi c database/GALT/GALT_display.php diagnosis, nursing considerations vary. An overview Berry, G. T. (2012). Galactosemia: When is it a newborn screening emergency? Molecular Genetics and Metabolism, 106(1), 7-11. of diagnosis-specifi c nursing implications is provided in doi:10.1016/j.ymgme.2012.03.007 Table 5. Berry, G. T. (2014). Classical galactosemia and clinical variant galacto- semia. In R. A. Pagon et al. (Eds.), Gene reviews. Seattle, WA: Uni- versity of Washington. Retrieved from https://www.ncbi.nlm.nih. Conclusion gov/books/NBK1518/ Newborn screening for galactosemia is complex and, de- Broomfi eld, A. A., Brain, C., & Gruenwald, S. (2011). Galactosaemia an spite decades of experience with screening, treatments update. Paediatrics and Child Health, 21(2), 65-70. doi:http://dx.doi. org/10.1016/j.paed.2010.10.003 and research, patient outcomes vary depending on galac- Coman, D. J., Murray, D. W., Byrne, J. C., Rudd, P. M., Bagaglia, P. M., tosemia type and there remains variability regarding pa- Doran, P. D., & Treacy, E. P. (2010). Galactosemia, a single gene disorder with epigenetic consequences. Pediatric Research, 67(3), tient management and monitoring. This emphasizes the 286-292. doi:10.1203/PDR.0b013e3181cbd542 importance of ongoing study to establish evidence-based Coss, K. P., Doran, P. P., Owoeye, C., Codd, M. B., Hamid, N., Mayne, practice guidelines and role nurses play during care of P. D., …, Treacy, E. P. (2013). Classical galactosaemia in Ireland: Incidence, complications and outcomes of treatment. Journal of these patients and families across the lifespan. Despite Inherited Metabolic Disease, 36(1), 21-27. doi:10.1007/s10545-012- evidence that questions the benefi ts of strict dietary 9507-9

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Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. Ficicioglu, C., Thomas, N., Yager, C., Gallagher, P. R., Hussa, C., Mattie, Powell, K. K., Van Naarden, B. K., Singh, R. H., Shapira, S. K., Olney, R. S., A., …, Forbes, B. J. (2008). Duarte (DG) galactosemia: A pilot study & Yeargin-Allsopp, M. (2009). Long-term speech and language devel- of biochemical and neurodevelopmental assessment in children opmental issues among children with Duarte galactosemia. Genetics detected by newborn screening. Molecular Genetics and Metabo- in , 11(12), 874-879. doi:10.1097/GIM.0b013e3181c0c38d lism, 95(4), 206-212. doi:10.1016/j.ymge.2008.09.005 Rubio-Agusti, I., Carecchio, M., Bhatia, K. P., Kojovic, M., Parees, I., Fridovich-Keil, J. L., & Walter, J. H. (2008). Galactosemia. In D. Valle Chandrashekar, H. S., …, Murphy, E. (2013). Movement disorders in et al. (Eds.), The online metabolic and molecular bases of adult patients with classical galactosemia. Movement Disorders, inherited disease-OMMBID, Part 7. New York, NY: McGraw-Hill 28(6), 804-810. doi:10.1002/mds.25348 [Chapter 72]. Sanders, R. D., Spencer, J. B., Epstein, M. P., Pollak, S. V., Vardhana, P. Hughes, J., Ryan, S., Lambert, D., Geoghegan, O., Clark, A., Rogers, Y., A., Lustbader, J. W., & Fridovich-Keil, J. L. (2009). Biomarkers of …, Treacy, E. P. (2009). Outcomes of siblings with classical galacto- ovarian function in girls and women with classic galactosemia. Fer- semia. The Journal of , 154(5), 721-726. doi:10.1016/j. tility and Sterility, 92(1), 344-351. doi:10.1016/j.fertnstert.2008.04.060 jpeds.2008.11.052 Varela-Lema, L., Paz-Valinas, L., Atienza-Merino, G., Zubizarreta-Alberdi, Mayatepek, E., Hoffmann, B., & Meissner, T. (2010). Inborn errors of R., Villares, R. V., & López-García, M. (2016). Appropriateness of . Best Practice & Research. Clinical Gas- newborn screening for classic galactosaemia: A systematic review. troenterology, 24(5), 607-618. doi:10.1016/j.bpg.2010.07.012 Journal of Inherited Metabolic Disease, 39(5), 633-649. doi:10.1007/ Mayo Clinic, Mayo Medical Laboratories. (n.d.). Galactosemia gene s10545-016-9936-y analysis (14-Mutation Panel). Retrieved from www.mayomedical Waisbren, S. E., Potter, N. L., Gordon, C. M., Green, R. C., Greenstein, laboratories.com/test-catalog/Overview/55071 P., Gubbels, C. S., …, Berry, G. T. (2012). The adult galactosemic Otaduy, M. C., Leite, C. C., Lacerda, M. T., Costa, M. O., Arita, F., Prado, phenotype. Journal of Inherited Metabolic Disease, 35(2), 279-286. E., & Rosemberg, S. (2006). Proton MR spectroscopy and imaging doi:10.1007/s10545-011-9372-y of a galactosemic patient before and after dietary treatment. Amer- Welling, L., Bernstein, L. E., Berry, G. T., Burlina, A. B., Eyskens, F., …, ican Journal of Neuroradiology, 27(1), 204-207. Bosch, A. M. (2017). International clinical guideline for the manage- Panis, B., Gerver, W. J., & Rubio-Gozalbo, M. E. (2007). Growth in treat- ment of classical galactosemia: Diagnosis, treatment, and follow- ed classical galactosemia patients. European Journal of Pediatrics, up. Journal of Inherited Metabolic Disease, 40(2), 171-176. 166(5), 443-446. doi:10.1007/s00431-006-0255-4 doi:10.1007/s10545-016-9990-5

For additional continuing nursing education activities related to maternal child nursing, go to nursingcenter.com/ce.

Instructions for Taking the CE Test Online GALT Defi ciency Galactosemia

• Read the article. The test for this CE activity can be taken Provider Accreditation: online at www.nursingcenter.com/ce/MCN. Tests can no LPD will award 1.5 contact hours for this continuing nursing longer be mailed or faxed. education activity. • You will need to create a free login to your personal LPD is accredited as a provider of continuing nursing CE Planner account before taking online tests. Your education by the American Nurses Credentialing Center’s planner will keep track of all your Lippincott Professional Commission on Accreditation. Development (LPD) online CE activities for you. This activity is also provider approved by the California • There is only one correct answer for each question. A Board of Registered Nursing, Provider Number CEP passing score for this test is 14 correct answers. If you 11749 for 1.5 contact hours. LPD is also an approved pass, you can print your certifi cate of earned contact provider of continuing nursing education by the District of hours and the answer key. If you fail, you have the Columbia, Georgia, and Florida CE Broker #50-1223. option of taking the test again at no additional cost. Payment: • For questions, contact LPD: 1-800-787-8985. Registration Deadline: February 29, 2020 • The registration fee for this test is $17.95. Disclosure Statement: The author and planners have disclosed no potential confl icts of interest, fi nancial or otherwise.

January/February 2018 MCN 51

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