Abstract
It has been 50 years since the first newborn screening (NBS) test for galactosemia was conducted in Oregon, and almost 10 years since the last US state added galactosemia to their NBS panel. During that time an estimated >2,500 babies with classic galactosemia have been identified by NBS. Most of these infants were spared the trauma of acute disease by early diagnosis and intervention, and many are alive today because of NBS. Newborn screening for galactosemia is a success story, but not yet a story with a completely happy ending. NBS, follow-up testing, and intervention for galactosemia continue to present challenges that highlight gaps in our knowledge. Here we compare galactosemia screening and follow-up data from 39 NBS programs gathered from the states directly or from public sources. On some matters the programs agreed: for example, those providing relevant data all identify classic galactosemia in close to 1/50,000 newborns and recommend immediate and lifelong dietary restriction of galactose for those infants. On other matters the programs disagree. For example, Duarte galactosemia (DG) detection rates vary dramatically among states, largely reflecting differences in screening approach. For infants diagnosed with DG, >80% of the programs surveyed recommend complete or partial dietary galactose restriction for the first year of life, or give mixed recommendations; <20% recommend no intervention. This disparity presents an ongoing dilemma for families and healthcare providers that could and should be resolved.
Competing interests: None declared
An erratum to this chapter is available at 10.1007/8904_2014_369
Errata to this chapter can be found at http://dx.doi.org/10.1007/978-3-662-43751-3_37010.1007/8904_2014_369
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References
Alano A, Almashanu S, Maceratesi P, Reichardt J, Panny S, Cowan TM (1997) UDP-galactose-4-epimerase deficiency among African-Americans: evidence for multiple alleles. J Investig Med 45:191A
Berry G (2012) Galactosemia: when is it a newborn screening emergency? Mol Genet Metab 106:7–11
Beutler E, Baluda M (1966) A simple spot screening test for galactosemia. J Lab Clin Med 68:137–141
Carney A, Sanders R, Garza K et al (2009) Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase. Hum Mol Genet 18:1624–1632
Coffee B, Hjelm L, DeLorenzo A, Courtney E, Yu C, Muralidharan K (2006) Characterization of an unusual deletion of the galactose-1-phosphate uridyl transferase (GALT) gene. Genet Med 8:635–640
Dobrowolski S, Banas R, Suzow J, Berkley M, Naylor E (2003) Analysis of common mutations in the galactose-1-phosphate uridyl transferase gene: new assays to increase the sensitivity and specificity of newborn screening for galactosemia. J Mol Diagn 5:42–47
Elsas LJ, Lai K, Saunders CJ, Langley SD (2001) Functional analysis of the human galactose-1-phosphate uridyltransferase promoter in Duarte and LA variant galactosemia. Mol Genet Metab 72:297–305
Fernhoff PM (2010) Duarte galactosemia: how sweet is it? Clin Chem 56:1045–1046
Ficicioglu C, Thomas N, Yager C et al (2008) Duarte (DG) galactosemia: a pilot study of biochemical and neurodevelopmental assessment in children detected by newborn screening. Mol Genet Metab 95:206–212
Freer D, Ficicioglu C, Finegold D (2010) Newborn screening for galactosemia: a review of 5 years of data and audit of a revised reporting approach. Clin Chem 56:437–444
Fridovich-Keil JL, Walter JH (2008) Galactosemia. In: Valle D, Beaudet A, Vogelstein B, Kinzler K, Antonarakis S, Ballabio A (eds) The online metabolic & molecular bases of inherited disease. McGraw Hill, http://www.ommbid.com/
Fridovich-Keil JL, Bean L, He M, Schroer R (2011) Epimerase deficiency galactosemia. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Stephens K (eds) GeneReviews™ [Internet]. University of Washington, Seattle, 1993–2013, http://www.ncbi.nlm.nih.gov/books/NBK51671/
Gethins M (2012) Breast cancer in men. J Natl Cancer Inst 104:436–438
Greber S, Guldberg P, Scheibenreiter S, Strobl W (1995) Mutations in classical and Duarte2 galactosemia. Pediatr Res 38:434 (abstract)
Gurian E, Kinnamon D, Henry J, SEW (2006) Expanded newborn screening for biochemical disorders: the effect of a false-positive result. Pediatrics 117:1915–1921
Hennermann J, Schadewaldt P, Vetter B, Shin Y, Mönch E, Klein J (2011) Features and outcome of galactokinase deficiency in children diagnosed by newborn screening. J Inherit Metab Dis 34:399–407
Janzen N, Illsinger S, Meyer U et al (2011) Early cataract formation due to galactokinase deficiency: impact of newborn screening. Arch Med Res 42:608–612
Kalaydjieva L, Perez-Lezaun A, Angelicheva D et al (1999) A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies). Am J Hum Genet 65:1299–1307
Leslie ND, Immerman EB, Flach JE, Florez M, Fridovich-Keil JL, Elsas LJ (1992) The human galactose-1-phosphate uridyl transferase gene. Genomics 14:474–480
Levy H, Sepe S, Walton D et al (1978) Galactose-1-phosphate uridly transferase deficiency due to Duarte/galactosemia combined variation: clinical and biochemical studies. J Pediatr 93:390
Mellman WJ, Tedesco TA, Feigl P (1968) Estimation of the gene frequency of the Duarte variant of galactose-1-phosphate uridyl transferase. Ann Hum Genet 32:1–8
Mohamad H, Apffelstaedt J (2008) Counseling for male BRCA mutation carriers – a review. Breast 17:441–450
Ohlsson A, Guthenberg C, von Döbeln U (2012) Galactosemia screening with low false-positive recall rate: the Swedish experience. JIMD Rep 2:113–117
Ono H, Mawatari H, Mizoguchi N, Eguchi T, Sakura N, Hamakawa M (1999) Transient galactosemia detected by neonatal mass screening. Pediatr Int 41:281–284
Ono H, Mawatari H, Mizoguchi N, Eguchi T, Sakura N, Hamakawa M (2000) Delay of liver maturation as a cause of transient neonatal galactosemia. Pediatr Int 42:61–63
Openo K, Schulz J, Vargas C et al (2006) Epimerase-deficiency galactosemia is not a binary condition. Am J Hum Genet 78:89–102
Podskarbi T, Kohlmetz T, Gathof BS et al (1996) Molecular characterization of Duarte-1 and Duarte-2 variants of galactose-1-phosphate uridyltransferase. J Inher Metab Dis 19:638–644
Powell KK, Van Naarden BK, Singh RH, Shapira SK, Olney RS, Yeargin-Allsopp M (2009) Long-term speech and language developmental issues among children with Duarte galactosemia. Genet Med 11:874–879
Raffel LJ, Cowan TM, Blitzer MG (1993) Transient neonatal galactosemia identified by newborn screening. J Inher Metab Disorders 16:894–895
Riehman K, Crews C, Fridovich-Keil JL (2001) Relationship between genotype, activity, and galactose sensitivity in yeast expressing patient alleles of human galactose-1-phosphate uridylyltransferase. J Biol Chem 276:10634–10640
Sangiuolo F, Magnani M, Stambolian D, Novelli G (2004) Biochemical characterization of two GALK1 mutations in patients with galactokinase deficiency. Hum Mutat 23:396–396
Suzuki M, West C, Beutler E (2001) Large-scale molecular screening for galactosemia alleles in a pan-ethnic population. Hum Genet 109:210–215
Tighe O, Flanagan JM, Kernan F et al (2004) Frequency distribution of the Los Angeles and Duarte galactose-1-phosphate uridyltransferase variant alleles in the Irish population. Mol Genet Metab 82:345–347
Trbusek M, Francova H, Kozak L (2001) Galactosemia: deletion in the 5′ upstream region of the GALT gene reduces promoter efficiency. Hum Genet 109:117–120
Tyfield LA (2000) Galactosaemia and allelic variation at the galactose-1-phosphate uridyltransferase gene: a complex relationship between genotype and phenotype. Eur J Pediatr 159(Suppl 3):S204–S207
van Calcar S, Bernstein L (2011) Nutrition management of classical and Duarte galactosemia: results from an international survey (Abstract). J Inherit Metab Dis 102:262 (Abstract P489)
Walter JH, Roberts REP, Besley GTN et al (1999) Generalised uridine diphosphate galactose-4-epimerase deficiency. Arch Dis Child 80:374–376
Wilcken B (2013) Newborn screening: gaps in the evidence. Science 342:197–198
Acknowledgments
This project would have been impossible without the help of many, many people who donated their time and shared information about their program’s newborn screening and follow-up testing experiences for galactosemia. We especially thank: Alicia Roberts and Danita Rollin (Alabama); Thalia Wood (Alaska); Hao Tang (California); Dan Wright and Erica Wright (Colorado); Patricia Scott and Louis Bartoshesky (Delaware); Lois Taylor, Bonifacio Dy, Charlie Williams, Penny Edwards, Lindsay Raub, and Helen McCune (Florida); Arthur Hagar, Angela Wittenauer, Luke Fiedorowicz, Kelli Rayford, and Johanna Pringle (Georgia); Tracey Kreipe (Illinois); Bryan Hainline (Indiana); Judy Miller (Iowa); Jamey Kendall and Julie Wellner (Kansas); Terry Crockett (Louisiana), Elizabeth Plummer and Eleanor Mulcahy (Maine); Carol Greene (Maryland); Karen Andruszewski, Harry Hawkins, Peggy Rush, and William Young (Michigan); Philis Hoggatt, Robert Wise, and Suzie Boyer (Mississippi); Jami Kiesling and Darla Aiken (Missouri); Sib Clack and Samuel Yang (Montana); Julie Luedtke and William Rizzo (Nebraska); Debbie Rodriguez and Joan Pellegrino (New York); Surekha Pendyal and Lara Percenti (North Carolina); Rosemary Hage (Ohio); David Koeller (Oregon, Alaska, Hawaii, Idaho, Nevada, and New Mexico); Kathy Tomashitis (South Carolina); Chris McKeever (Tennessee); Stephanie Sanborn, Caroline Homer, and Lindsay Toole (Texas); Kim Hart (Utah); Cindy Ingham and Leah Burke (Vermont); Kristel Fijolek (West Virginia); and Gary Hoffman (Wisconsin). We are also especially indebted to Dr. Brad Therrell of the National Newborn Screening Information System (http://nnsis.uthscsa.edu) for his encouragement and support of this project, and to the University of Texas Health Sciences Center for providing initial funding for this work (Award# 0000017221, PI: Fridovich-Keil).
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Communicated by: Bridget Wilcken
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All the authors of this chapter declare that there are no conflicts of interest.
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“All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5).”
No data from specific individuals are included in this study and so no one signed an informed consent form to participate.
Please note that this study was approved by both the Emory University Institutional Review Board (IRB# 00024933, PI: Fridovich-Keil) and the Georgia Department of Public Health Institutional Review Board (GA PDH IRB# 130306, PI: Fridovich-Keil). Data accessed from the Emory Genetics Lab MEDGIS database were ascertained through a HIPAA waiver granted by the Emory IRB (under IRB# 00024933).
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Contributions of Each Author
Brook Pyhtila conducted most of the data gathering, performed some of the data analysis, and participated in writing and editing the manuscript.
Kelly Shaw performed some of the data gathering, performed some of the data analysis, and participated in editing the manuscript.
Samantha Neumann performed some of the data gathering and participated in editing the manuscript.
Judith Fridovich-Keil originated the project, oversaw the data gathering and analysis, wrote and edited most of the manuscript, and coordinated the contributions of the other authors.
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Newborn screening for galactosemia in the USA is a success story, but significant challenges remain.
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Pyhtila, B.M., Shaw, K.A., Neumann, S.E., Fridovich-Keil, J.L. (2014). Newborn Screening for Galactosemia in the United States: Looking Back, Looking Around, and Looking Ahead. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports, Volume 15. JIMD Reports, vol 15. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_302
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DOI: https://doi.org/10.1007/8904_2014_302
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