Development of a Questionnaire Method of Screening for Citrin Deficiency in Schoolchildren

Citrin deficiency is a congenital metabolic disorder of autosomal recessive inheritance that is caused by mutations in the SLC25A13 gene. The prevalence of homozygotes of these mutations is 1/17,000, with a corresponding prevalence of 0.015 for heterozygotes 5 in Japan. It is difficult to detect citrin deficiency before the onset of adult onset type II citrullinemia (CTLN2) during the asymptomatic period. To detect citrin deficiency during the asymptomatic period, we distributed a parent-administered questionnaire, which focused on specific food preferences of disliking sweets and preferring high protein and high fat foods, to 62,895 children in elementary and junior high school. We obtained 16,468 responses, and 84 children had these specific food preferences. After excluding children whose parents did not want a telephone contact and those without available contact details, we asked the parents of 32 children if they would allow their child to undergo a genetic test of the SLC25A13 gene. DNA extracted from the collected saliva of these 13 children was examined for 6 prevalent mutations in the SLC25A13 gene. Although two of these 13 children were heterozygous carriers, one child with c.851_854delGTAT and one with c.1177+1G>A, no homozygous carrier was detected. We plan to expand the number of study subjects to improve the questionnaire screening for citrin deficiency in an ongoing genome cohort study.