Lumasiran at birth changes the trajectory of primary hyperoxaluria type 1: same disease, different outcomes in two affected siblings

TL;DR

Treating a newborn with lumasiran immediately after birth prevented severe symptoms of primary hyperoxaluria type 1, unlike in his older brother who developed complications.

Contribution

This is the first report of oxalate and glycolate metabolism in a newborn with primary hyperoxaluria type 1 treated with lumasiran at birth.

Findings

Early treatment with lumasiran and supportive care prevented symptoms of primary hyperoxaluria type 1 in a newborn over 24 months.

Blood oxalate supersaturation was avoided after 30 days of treatment initiation.

No adverse events were observed with the treatment regimen.

Abstract

Lumasiran, an RNA interference therapeutic, demonstrated effectiveness in clinical trials, leading to approval for primary hyperoxaluria type 1 management in all age groups. To date, little is known about its use in newborns. This study assesses, for the first time, the oxalate and glycolate metabolism in a newborn affected by primary hyperoxaluria type 1 treated at birth. His older brother, also affected by primary hyperoxaluria type 1, experienced severe disease progression and significant comorbidities. These challenges informed the decision to initiate immediate treatment for the younger sibling. The child was treated at 6 h of life with lumasiran 6 mg/kg subcutaneously, in combination with pyridoxin 10 mg/kg/day. Lumasiran 6 mg/kg was repeated at 30 and 60 days, then was reduced to 3 mg/kg every month. Intravenous hyperhydration (240 mL/kg/day) was maintained for 16 days, together with oral water and potassium citrate (500 mg in 500 mL/day) in addition to breastfeeding. Although gycolate oxidase inhibition was started immediately after birth in the absence of previous deposits, it showed a latency of at least 15 days. Over this period of time, dangerous levels of blood and urinary oxalate were reached, due to the physiological low glomerular filtration rate in the perinatal period, as demonstrated by the increasing levels of endogenous oxalate production until day 6. Blood oxalate supersaturation 30 days after the first dose of treatment was never reached again. No adverse events occurred. In this report, early treatment with lumasiran, coupled with hyperhydration and supportive therapy, was able to ensure the absence of primary hyperoxaluria type 1 symptoms throughout the 24 months of follow-up.

The online version contains supplementary material available at 10.1007/s40620-025-02325-2.

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