Determination of optimal cutoff value to accurately identify glucose-6-phosphate dehydrogenase-deficient heterozygous female neonates

Miao, Jing-Kun; Chen, Qi-Xiong; Bao, Liming; Huang, Yi; Zhang, Juan; Wan, Ke-Xing; Jing, Y. P.; Wang, Shiyi; Zou, Lin; Li, Tingyu

doi:10.1016/j.cca.2013.05.004

Cited by 11 publications

(14 citation statements)

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“…Distributions of G6PD activities in neonates reported in literature show separation into 2 groups (deficient and nondeficient) for males but no clear separation for females (13,15,19). However, in studies of broader age-groups (9,20) or more diverse populations (14), the separation between groups is less defined even for males.…”

Section: Discussionmentioning

confidence: 94%

“…Enzymatic activity screening tests generally have a high diagnostic sensitivity and specificity for detecting severely deficient hemizygous males and homozygous females but a lower sensitivity for detecting G6PD 3 mutation heterozygous females who have a range of G6PD activities because of random X-inactivation. Higher activity cutoffs may allow identification of more heterozygous female neonates (13).…”

mentioning

confidence: 99%

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Genotype–Phenotype Correlations of Glucose-6-Phosphate–Deficient Variants Throughout an Activity Distribution

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Grenache

2018

The Journal of Applied Laboratory Medicine

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Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked disorder that may manifest as neonatal jaundice or acute hemolytic anemia. Quantitative assessment of G6PD activity in erythrocytes is required to definitively diagnose a deficiency. Most males and homozygous females have low enzyme activities, whereas heterozygous females may have a range of activities. We sought to examine G6PD genotype-phenotype associations to identify an activity cutoff above which G6PD deficiency is unlikely. Methods: Ninety-five residual samples were randomly selected to represent the various regions of a G6PD activity distribution. DNA was isolated from the leukocyte fraction and sequenced using the Sanger method. ROC curves were used to establish cutoffs. Results: Thirteen variant alleles were identified, including 1 not previously reported. In the very deficient activity range, we found males and homozygous females of both class II and III variants. In the deficient category, we found predominantly class III males and heterozygous females. The presumed deficient category contained class III and IV variants and nonvariants. An activity cutoff of <7.85 U/g hemoglobin (Hb) was 100% sensitive and 94% specific for identifying a G6PD-deficient male, and a cutoff of <8.95 U/g Hb was 90% sensitive and 82% specific for a deficient female. Conclusions: The observed activity groupings were not because of a particular variant class. Cutoffs to identify the presence of a deficiency variant for males and females may be useful when trying to decide whether to recommend genetic analysis. IMPACT STATEMENT Although most glucose-6-phosphate dehydrogenase (G6PD)-deficient males and homozygous females have low G6PD activities, heterozygous females and some males have activities that may or may not suggest deficiency. After sequencing of the exon region of samples within each area of an activity distribution, we prepared ROC curves to identify activity cutoffs above which a deficiency is unlikely. A cutoff with 100% sensitivity and 94% specificity was identified for males, whereas a cutoff with 90% sensitivity and 82% specificity was identified for females.

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

Genotype–Phenotype Correlations of Glucose-6-Phosphate–Deficient Variants Throughout an Activity Distribution

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Grenache

2018

The Journal of Applied Laboratory Medicine

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“…Various methods may improve heterozygote detection. 20,22 For example, we improved qualitative screening sensitivity by assessing decolorization at 30 minutes, which detected most heterozygotes, including six of eight with normal activity. However, this also identified two normal subjects.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, because no firm correlation exists between G6PD level and clinical phenotype, some suggest that all heterozygous females be defined as G6PD deficient. [20][21][22] Although definitive, genetic testing is complex. G6PD contains 13 exons encoding a 515-amino acid protein; most *Address correspondence to Julia Z. Xu, Department of Medicine, Duke University Medical Center, 2301 Erwin Road, Box 3182, Durham, NC 27710.…”

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confidence: 99%

G6PD Deficiency in an HIV Clinic Setting in the Dominican Republic

Francis

Nadal

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. Because human immunodeficiency virus (HIV)-infected patients receive prophylaxis with oxidative drugs, those with glucose-6-phosphate dehydrogenase (G6PD) deficiency may experience hemolysis. However, G6PD deficiency has not been studied in the Dominican Republic, where many individuals have African ancestry. Our objective was to determine the prevalence of G6PD deficiency in Dominican HIV-infected patients and to attempt to develop a cost-effective algorithm for identifying such individuals. To this end, histories, chart reviews, and G6PD testing were performed for 238 consecutive HIV-infected adult clinic patients. The overall prevalence of G6PD deficiency (8.8%) was similar in males (9.3%) and females (8.5%), and higher in Haitians (18%) than Dominicans (6.4%; P = 0.01). By logistic regression, three clinical variables predicted G6PD status: maternal country of birth (P = 0.01) and a history of hemolysis (P = 0.01) or severe anemia (P = 0.03). Using these criteria, an algorithm was developed, in which a patient subset was identified that would benefit most from G6PD screening, yielding a sensitivity of 94.7% and a specificity of 97.2%, increasing the pretest probability (8.8-15.1%), and halving the number of patients needing testing. This algorithm may provide a cost-effective strategy for improving care in resource-limited settings.

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“…Esta característica es relevante puesto que como señalan otros autores tiene influencia en el valor de corte del tamiz, mismo que debe categorizarse por sexo. 22,35 En México se han efectuado contribuciones significativas al conocimiento de la deficiencia de G6PD, en particular en sus aspectos funcionales, bioquímicos y epidemiológicos. 2,36,37 La Cuadro 3.…”

Section: Discussionunclassified

Valores de glucosa-6-fosfato deshidrogenasa y su repercusión en el número de sospechas de tamiz neonatal

et al. 2018

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INTRODUCCIÓN: La deficiencia de glucosa-6-fosfato deshidrogenasa (dG6PD) es la enzimopatía hereditaria más frecuente en el mundo. La mayoría de los casos son asintomáticos y algunos llegan a padecer anemia hemolítica aguda, ictericia neonatal o anemia hemolítica crónica no esferocítica. En países de Asia y el Mediterráneo y con alta incidencia de malaria, se practica el tamiz neonatal para la dG6PD, pero no existe un consenso universal para su implementación. OBJETIVO: Describir los valores de la actividad de G6PD en papel filtro en recién nacidos, analizar la prevalencia y la repercusión en el número de localizaciones a efectuar en el programa de tamiz neonatal nacional.MATERIAL Y MÉTODOS: Estudio retrospectivo de los resultados del programa de tamiz neonatal de la Secretaría de Salud de México. Se analizó la actividad de la glucosa- 6-fosfato deshidrogenasa dependiendo del tiempo de tránsito (tiempo trascurrido desde la obtención de la muestra de sangre del talón del recién nacido hasta su llegada al laboratorio). Se analizó la prevalencia según la actividad enzimática residual.RESULTADOS: De 1,076,918 recién nacidos tamizados, 343,272 tuvieron tiempo de tránsito adecuado (≤ 6 días). La actividad enzimática desciende significativamente después de ese tiempo. La prevalencia nacional al nacimiento fue de 4.26%, con porcentajes máximos en Veracruz, Nuevo León y Tabasco (21,20 y 15%, respectivamente). CONCLUSIÓN: 4.26% de los recién nacidos en México tienen dG6PD; es decir, un caso por cada 23 tamizados, lo que implica un elevado número de sujetos para localizar y evaluar en los programas de tamiz neonatal y en las instituciones que llevan a cabo el seguimiento clínico.PALABRAS CLAVE: Glucosa 6-fosfato deshidrogenasa, deficiencia de glucosa 6-fosfato deshidrogenasa, tamiz neonatal, prevalencia.

show abstract

Determination of optimal cutoff value to accurately identify glucose-6-phosphate dehydrogenase-deficient heterozygous female neonates

Cited by 11 publications

References 28 publications

Genotype–Phenotype Correlations of Glucose-6-Phosphate–Deficient Variants Throughout an Activity Distribution

Genotype–Phenotype Correlations of Glucose-6-Phosphate–Deficient Variants Throughout an Activity Distribution

G6PD Deficiency in an HIV Clinic Setting in the Dominican Republic

Valores de glucosa-6-fosfato deshidrogenasa y su repercusión en el número de sospechas de tamiz neonatal

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