SLC25A13 c.1610_1612delinsAT mutation in an Indian patient and literature review of 79 cases of citrin deficiency for genotype-phenotype associations

Abstract

Here, we report SLC25A13 c.1610_1612delinsAT mutation from India in a 13-year old boy who presented with recurrent episodes of delirium and hyperammonemia. This is the second case with this mutation; the first case was of Pakistani origin. The boy responded to diet modification, sodium benzoate and arginine supplementation. Furthermore, we have aimed to establish genotype-phenotype correlation of 79 cases of citrin deficiency (46 males and 33 females) reported in 24 studies from all over the world. Inverse association was observed between age of onset and jaundice (r = −0.73). Late age of onset was associated with delirium (r = 0.61), aggressive behaviour (r = 0.67), altered sensorium (r = 0.67) and tremors (r = 0.65). The most common mutations associated with citrin deficiency were c.851_854del4, IVS16ins3kb, 1638-1660dup with a frequency of 42.41%, 16.46% and 6.33%, respectively. The c.851_854del4 mutation showed positive association with alpha feto protein (r = 0.40), ammonia (r = 0.50) and tyrosine (r = 0.40) while showing inverse association with threonine (r = −0.55). The IVS16ins3kb mutation was associated with high total (r = 0.65) and conjugated bilirubin (r = 0.54) along with high aspartate transaminase (r = 0.49) while citrulline levels are lower (r = −0.36). To conclude, all cases of intrahepatic cholestasis and neuropsychiatric abnormalities should be evaluated for citrin deficiency. However, the ethnic group-specific mutation frequencies should be considered in implementing screening.