Neonatal Classic Galactosemia in North India: A 7-Year Cohort Study of Presentation, Genetics, and Outcomes

Purpose Classic galactosemia (CG) is an autosomal recessive inborn error of galactose metabolism, caused by a profound deficiency of galactose-1-phosphate uridyltransferase (GALT). Neonates affected by CG may appear healthy at birth but develop severe, life-threatening symptoms shortly after milk feeding begins. Common early signs include jaundice, hepatomegaly, feeding intolerance, vomiting, and sepsis. Early diagnosis and intervention with a galactose-free diet are essential to prevent acute liver failure, sepsis, and death. However, even with early treatment, long-term complications, including neurodevelopmental impairments and ovarian failure, are prevalent. In regions without newborn screening programs, diagnosis is frequently delayed. This study aimed to retrospectively characterize the clinical profile, diagnostic approach, genetic spectrum, incidence, and outcomes of neonatal classic galactosemia in a North Indian tertiary center. Methods Medical records of neonates (≤ 28 days) diagnosed with CG at Sher-i-Kashmir Institute of Medical Sciences (SKIMS) from January 2018 to December 2025 were reviewed. Inclusion criteria required clinical features consistent with CG, confirmed by near-absent erythrocyte GALT activity and/or pathogenic mutations in both GALT alleles. Clinical data, laboratory results (bilirubin, liver enzymes, coagulopathy, and culture findings), treatments, and outcomes were recorded. Genetic testing was performed when available. Descriptive statistical methods were used for data analysis. Results Eighteen neonates (10 males, 8 females) were identified, representing approximately 2.5% of neonatal cholestasis cases. Parental consanguinity was present in 5 (28%) cases. The median age at symptom onset was 9 days (range 3–21), and the median age at diagnosis was 19 days (range 7–45). Jaundice was present in all infants, with hepatomegaly in 89%. Poor feeding and lethargy were common in 83% of cases, while vomiting was noted in 67%. Sepsis, primarily due to Escherichia coli , occurred in 9 (50%) infants. Cataracts were observed in 5 (28%). Laboratory tests showed cholestatic jaundice, with a median total bilirubin of 18 mg/dL and elevated liver enzymes (AST and ALT 3–10× normal). Coagulopathy (INR > 2) was noted in 6 (33%) infants. All infants received a lactose-free diet, supportive care, antibiotics, and blood products as needed. No exchange transfusions were required. Genetic testing identified 7 distinct GALT mutations, with p.Gln188Arg (Q188R) as the most frequent. Clinically, all patients improved with the galactose-free diet. Three neonatal deaths (17%) occurred, all in infants presenting after 3 weeks with severe sepsis and multiorgan failure. The remaining 15 (83%) survived to discharge. At a median follow-up of 12 months, all survivors had normal liver function, but 3 exhibited mild developmental delays, and one female showed early ovarian insufficiency. Conclusions Neonatal classic galactosemia remains a severe disorder with high mortality if diagnosis is delayed. Prompt recognition and dietary management lead to favorable short-term outcomes. In regions lacking newborn screening, early testing for galactosemia in neonates with cholestatic jaundice or sepsis could prevent fatalities. Our study highlights the genetic diversity in the cohort, underscoring the need for comprehensive genetic analysis. Long-term follow-up is crucial, as survivors may face developmental and reproductive challenges. The findings support the implementation of newborn screening for galactosemia in India to improve outcomes for affected infants.