Genetic spectrum and clinical early natural history of glucose-6-phosphate dehydrogenase deficiency in Mexican children detected through newborn screening.

backgroundGlucose-6-phosphate dehydrogenase deficiency (G6PDd) newborn screening is still a matter of debate due to its highly heterogeneous birth prevalence and clinical expression, as well as, the lack of enough knowledge on its natural history. Herein, we describe the early natural clinical course and the underlying GDPD genotypes in infants with G6PDd detected by newborn screening and later studied in a single follow-up center. G6PDd newborns were categorized into three groups: group 1: hospitalized with or without neonatal jaundice (NNJ); group 2: non-hospitalized with NNJ; and group 3: asymptomatic. Frequencies of homozygous UGT1A1*28 (rs34983651) genotypes among G6PDd patients with or without NNJ were also explored.

resultsA total of 81 newborns (80 males, one female) were included. Most individuals (46.9%) had NNJ without other symptoms, followed by asymptomatic (42.0%) and hospitalized (11.1%) patients, although the hospitalization of only 3 of these patients was related to G6PDd, including NNJ or acute hemolytic anemia (AHA). Nine different G6PDd genotypes were found; the G6PD A

conclusionWide variability in residual enzymatic activity was noted in G6PDd individuals with the same G6PD genotype. This feature, along with a documented heterogeneous mutational spectrum, makes it difficult to categorize G6PD variants according to current WHO classification and precludes the prediction of complications such as AHA, which can occur even with > 10% of residual enzymatic activity and/or be associated with the common and mild G6PD A