Newborn screening: A disease-changing intervention for glutaric aciduria type 1

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Glutaric aciduria type 1 (GA1) untreated leads to movement disorders due to striatal damage.
• Newborn screening (NBS) has improved short-term GA1 outcomes, but long-term effects and predictive variables remain unclear.

Purpose of the Study:

• To evaluate the long-term impact of NBS on glutaric aciduria type 1 (GA1) outcomes.
• To identify variables predicting neurological and non-neurological outcomes in GA1 patients.

Main Methods:

• A prospective, observational, multicenter study included 91 GA1 patients (87 NBS-identified, 4 missed) and 3 mothers.
• The study captured 98.3% of NBS-identified GA1 cases in Germany from 1999-2016.

Main Results:

• NBS cumulative sensitivity is 95.6%, lower for the low excreter phenotype (84%).
• Presymptomatic treatment significantly improves neurological outcomes (7% with movement disorder), while delayed or inconsistent treatment leads to higher rates (100% and 50%).
• Kidney function declines with age, irrespective of neurological phenotype or treatment adherence.

Conclusions:

• NBS is a beneficial intervention for GA1, but optimal neurological outcomes depend on strict adherence to recommended therapies.
• Recommended therapies do not appear to impact the age-related decline in kidney function observed in GA1 patients.