A 10-week-old infant is referred to your clinic after the parents notice a “white reflex” in the baby’s eyes on photographs. The parents have no other concerns. He was born at term and is exclusively breastfed with appropriate weight gain. There is no jaundice, hepatosplenomegaly, vomiting, lethargy, or other developmental concerns. Family history is insignificant on the mother’s side. It is unknown on the father’s side, as he was adopted, but both are from the same region of Turkey. Vital signs are within normal limits. The exam is benign besides bilateral leukocoria, with dilated exam revealing bilateral central lens opacities with a surrounding clear cortex. There is no corneal clouding. CBC, CMP, liver function, ammonia, and coagulation studies came back normal. Routine UA was also unremarkable.
What would be the best next step in diagnostic workup?
Correct answer: C urine copper-reduction test
This infant most likely has galactokinase (GALK1) deficiency due to the clinical combination of bilateral cataracts with leukocoria without any other severe features or other laboratory disorders. This infant is thriving with exclusive breastfeeding which provides a source of galactose. GALK1 deficiency is a relatively rare disease that is inherited autosomal recessively. With both parents being from the same region of Turkey, there is some likelihood of consanguinity that could have contributed to this disease. GALK1 deficiency is characterized by inability to break down galactose which causes it and its byproducts to accumulate, one of which being galactitol in the lens causing a cataract. Classical galactosemia would also cause this but often causes liver disease, coagulopathy, and failure to thrive. Routine UA is “unremarkable” because the standard dipstick is specific for glucose and does not react with galactose. A urine copper-reduction (Clinitest/Benedict) test detects any reducing sugar and will be positive for the non-glucose reducing substance (galactose). This serves as the fastest and cheapest next step for confirming this diagnosis rather than urinary galactitol measurement or GALK1 enzyme kinetics.
A) Repeating the dipstick changes nothing; the glucose-oxidase chemistry will remain negative since it only reduces glucose.
B) Leukocoria mandates excluding retinoblastoma, but the dilated exam here already identifies bilateral central lens opacities (cataract) as the cause of the white reflex, with a normal view and no mass. Also, retinoblastoma classically produces a retinal mass/calcification, not a lens opacity. B-scan and RB1 testing are not the best next step once a cataract is visualized as the source.
D) Coats disease is almost always unilateral in young boys with subretinal lipoprotein exudate, not a bilateral lens opacity. It Coats is a retinal, not lenticular, cause of leukocoria.
E) Although this is a reasonable choice in bilateral cataract workup, TORCH cataracts usually accompany other stigmata (IUGR, hepatosplenomegaly, rash, microcephaly), which are all absent here.
Cerone J, Rios A. Galactosemia. Pediatr Rev. 2019 Oct;40(Suppl 1):24-27. doi: 10.1542/pir.2018-0150. Epub 2019 Oct 1. PMID: 31575690.