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

  • Grace Stuhrman
  • Stefanie J. Perez Juanazo
  • Kea Crivelly
  • Jennifer Smith
  • Hans Andersson
  • Eva Morava
Case Report
Part of the JIMD Reports book series (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.

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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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Grace Stuhrman
    • 1
  • Stefanie J. Perez Juanazo
    • 1
  • Kea Crivelly
    • 1
  • Jennifer Smith
    • 1
  • Hans Andersson
    • 1
  • Eva Morava
    • 1
  1. 1.Hayward Genetics CenterTulane University School of MedicineNew OrleansUSA

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