Glucose-6-phosphate dehydrogenase deficiency in female octogenarians, nanogenarians, and centenarians.
BACKGROUND
Age-related skewing of X-chromosome inactivation leading to glucose-6-phosphate dehydrogenase (G6PD) deficiency in elderly women in a population with prevalent G6PD gene mutations was investigated.


METHODS
G6PD activity was measured biochemically. G6PD mutations were detected by polymerase chain reaction (PCR) and allele-specific extension, and analyzed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and Sequenom MassARRAY. X-chromosome inactivation was quantified by semiquantitative PCR for the HUMARA gene, before and after HpaII digestion.


RESULTS
In 173 women (median age: 90 years; range, 80-107 years), 18 heterozygotes for G6PD mutations were identified. Three heterozygotes were G6PD deficient, owing to skewed X-chromosome inactivation affecting the wild-type allele. Fifteen heterozygotes, with skewing apparently affecting the mutant alleles, had normal but significantly lower G6PD levels. At 1.73%, G6PD deficiency was significantly more frequent than expected from population screening at birth.


CONCLUSIONS
Due to skewed X-chromosome inactivation, elderly women in populations with prevalent G6PD mutations are at risk of G6PD deficiency.
Au
Wing-Yan
WY
Department of Medicine, Professorial Block, Queen Mary Hospital, Pokfulam Road, Hong Kong.
Lam
Veronica
V
Pang
Annie
A
Lee
Wing-Man
WM
Chan
Jess L C
JL
Song
You-Qiang
YQ
Ma
Edmond S
ES
Kwong
Yok-Lam
YL
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D009154:Mutation; D010641:Phenotype; D049951:X Chromosome Inactivation
D005954:Glucosephosphate Dehydrogenase