What are the indications for glucose-6-phosphate dehydrogenase (G6PD) deficiency screening, and what are the guidelines for laboratory testing from the British Society for Haematology?

Updated: Jun 25, 2020
  • Author: Lawrence C Wolfe, MD; Chief Editor: George T Griffing, MD  more...
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Answer

A semi-quantitative test is usually indicated in patients with a suggestive family history or in geographical areas with a high prevalence of the disorder. Positive screening results should be confirmed by quantitative tests. Diagnosis of G6PD may be difficult in females, who may be hemizygous or have skewed X chromosome inactivation or G6PD gene mosaicism.

G6PD activity is higher in premature infants than in term infants. This should be considered when testing for G6PD deficiency in infants.

Guidelines

Guidelines on the laboratory diagnosis of G6PD deficiency, published in January 2020 by the British Society for Haematology, include the following [38] :

  • Screening tests should not be relied on for the diagnosis of female patients; G6PD activity should be measured directly by quantitative spectrophotometric assay
  • An abnormal or borderline screening test means that a quantitative assay must be performed
  • To be certain that a G6PD-deficiency diagnosis is not missed, re‐assay after a hemolytic episode of unknown cause
  • Because the G6PD reaction is temperature‐dependent, an accurate cuvette temperature is essential
  • Controls should be run with every sample batch; it is preferable to use a normal and deficient sample obtained through a commercial company than to employ an in‐house control
  • White cells, which contain a significant amount of G6PD, ideally should be removed before assay; especially consider removal of white cells with a cellulose/”real” cotton wool column prior to assay if the count is above the lab’s reference interval upper limit
  • If performed only infrequently, carry out assays in duplicate; the duplicates’ results, on normal samples, should be within 0.5 IU/g of hemoglobin of each other
  • Employ in-house testing to establish a laboratory reference range
  • Assay absorbance should be checked to see that it increases in a linear fashion (which may take a minute or two to achieve), and, for non-kit methods, the absorbance should be measured over 10 minutes at 20-second intervals
  • Measurement of the hemoglobin concentration of the hemolysate is equal in importance to measurement of the enzyme activity, since both measurements have a comparable impact on the final result; this applies similarly to well-mixed whole blood where a kit indicates such use
  • Interpret the final G6PD activity in light of the reticulocyte count measured on the same sample
  • Participation in an accredited external quality assessment scheme is important for laboratories undertaking these screening tests and assays

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