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False-Positive Newborn Screen Using the Beutler Spot Assay for Galactosemia in Glucose-6-Phosphate Dehydrogenase Deficiency

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JIMD Reports, Volume 36

Part of the book series: JIMD Reports ((JIMD,volume 36))

Abstract

Classical galactosemia is detected through newborn screening by measuring galactose-1-phosphate uridylyltransferase (GALT) in the USA primarily via the Beutler spot assay. We report on an 18-month-old patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency that was originally diagnosed with classical galactosemia. The patient presented with elevated liver function enzymes and bilirubinemia and was immediately treated with soy-based formula. Confirmatory tests revealed deficiency of the GALT enzyme, however, full-sequencing of GALT was normal, suggestive of a different ideology. The Beutler spot assay uses three other enzymatic steps in addition to GALT. A deficiency in either of these enzymes can result in suspected decreased GALT activity when using the Beutler assay. Congenital Disorders of Glycosylation screening for phosphoglucomutase-1 deficiency was negative. Quantitative analysis of G6PD enzyme in red blood cells showed a severe deficiency and a deletion in G6PD. Soy-formula, the standard treatment for galactosemia, has been reported to trigger hemolysis in G6PD deficient patients. G6PD and phosphoglucomutase-1 deficiencies should be considered when confirmatory tests are negative for pathogenic variants in GALT and galactose-1-phosphate level is normal.

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Abbreviations

6PGD:

6-Phosphogluconate dehydrogenase

ALT:

Alanine transaminase

AST:

Aspartate aminotransferase

CBC:

Complete blood count

CDG:

Congenital disorders of glycosylation

dl:

Deciliter

G6PD:

Glucose-6-phosphate dehydrogenase

Gal-1-P:

Galacose-1-phosphate

GALT:

Galactose-1-phosphate uridylyltransferase

Hb:

Hemoglobin

hr:

Hour

IU:

International unit

μmol:

Micromole

mg:

Milligram

ml:

Milliliter

NADP+ :

Nicotinamide adenine dinucleotide phosphate

NADPH:

Nicotinamide adenine dinucleotide phosphate

NBS:

Newborn screening

PGM1:

Phosphoglucomutase-1

U/g:

Units per gram

UDP-glucose:

Uridine diphosphate glucose

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Author information

Authors and Affiliations

  1. Hayward Genetics Center, Tulane University School of Medicine, 1430 Tulane Ave., Mailbox #8631, New Orleans, LA, 70112, USA

    Grace Stuhrman, Stefanie J. Perez Juanazo, Kea Crivelly, Jennifer Smith, Hans Andersson & Eva Morava

Authors
  1. Grace Stuhrman
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  2. Stefanie J. Perez Juanazo
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  3. Kea Crivelly
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  4. Jennifer Smith
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  5. Hans Andersson
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  6. Eva Morava
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Corresponding author

Correspondence to Grace Stuhrman .

Editor information

Editors and Affiliations

  1. Tulane University Medical School, New Orleans, Louisiana, USA

    Eva Morava

  2. Division of Metabolism and Children’s Research Centre, University Children’s Hospital Zurich, Zurich, Switzerland

    Matthias Baumgartner

  3. Division of Child and Adolescent Neurology, Mayo Clinic, Rochester, Minnesota, USA

    Marc Patterson

  4. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom

    Shamima Rahman

  5. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  6. Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Daniela Karall

Appendices

Synopsis

Decreased GALT enzyme by Beutler spot assay can mask PGM1 or G6PD deficiencies and warrants further metabolic analysis in the absence of pathogenic variants in GALT. Soy-based formula intake can trigger hemolysis in G6PD deficiency.

Compliance with Ethics Guidelines

Conflict of Interest

Grace Stuhrman, Stefanie J. Perez Juanazo, Kea Crivelly, Jennifer Smith, Dr. Hans Andersson and Dr. Eva Morava declare that they have no conflicts of interest.

Informed Consent/Animal Rights

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). This article does not contain any studies with animal subjects performed by the any of the authors.

Details of the Contributions of Individual Authors

Grace Stuhrman drafted the initial manuscript and revised the manuscript.

Stefanie J. Perez Juanazo contributed to drafting the initial manuscript and conducted biochemical assays.

Jennifer Smith conducted biochemical assays.

Kea Crivelly, Eva Morava-Kozicz, and Hans Andersson critically reviewed and revised the manuscript.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Stuhrman, G., Perez Juanazo, S.J., Crivelly, K., Smith, J., Andersson, H., Morava, E. (2017). False-Positive Newborn Screen Using the Beutler Spot Assay for Galactosemia in Glucose-6-Phosphate Dehydrogenase Deficiency. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 36. JIMD Reports, vol 36. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_34

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  • DOI: https://doi.org/10.1007/8904_2016_34

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-56137-9

  • Online ISBN: 978-3-662-56138-6

  • eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

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