Clinical profile and thiamine transporter gene (SLC19A2 and SLC19A3) variations in infants with thiamine-responsive pulmonary hypertension and acute respiratory infection.

Maternal thiamine deficiency is prevalent in low- and middle-income countries. Thiamine-responsive pulmonary hypertension (TRPHTN) in exclusively breastfed infants is reported in India. Thiamine transporter gene (ThTR) variations have not been studied. This study compared the presentation of exclusively breastfed infants with respiratory distress diagnosed as TRPHTN or acute respiratory infection (ARI). We investigated pathogenic variations in the SLC19A2 and SLC19A3 ThTr genes in a representative sample. Observational study. Tertiary care pediatric unit of a teaching hospital in southern India. Data collection was prospective. We included exclusively breastfed infants between 1 and 6 months of age with respiratory distress. Infants with PHTN in echocardiography and lactic acidosis (LA) received thiamine. TRPHTN was diagnosed based on response within 72 h. Infants with fever, chest findings, and positive microbiology were managed as ARI. The ThTr genes were sequenced and analyzed. Chi-square and stratified analysis were done to determine TRPHTN risk. Forty infants with TRPHTN and 42 with ARI were included. The median pulmonary arterial pressure in the TRPHTN group was 51.5 mmHg. Mild PHTN was seen in 65%, moderate in 22.5%, and severe in 12.5%. Cardiac failure (P < .001), stridor and aphonia (P < .001), encephalopathy (P = .024), LA (P < .001), and PHTN (P <.001) facilitated the diagnosis. The adjusted risk was 17.3 (95% confidence interval 7.8-38.3; P <.001). The ThTR sequencing showed wild-type genotypes. TRPHTN has a distinct, identifiable presentation. Lactate and pulmonary pressure estimations are useful investigations in thiamine deficiency endemic areas. We could not demonstrate a genetic variation that determines susceptibility.