What Is Hereditary Orotic Aciduria?

The FDA recently approved uridine triacetate (Xuriden), a treatment for a rare condition called hereditary orotic aciduria.

Orotic aciduria refers to an excessive excretion of orotic acid in the urine. Orotic acid is an intermediate product produced during the pyrimidine synthesis pathway.

The inability to convert orotic acid results in the body being unable to normally synthesize uridine, a necessary component of RNA, which ultimately leads to a failure to thrive.¹

Hereditary orotic aciduria is a rare autosomal recessive disorder. A heterozygous patient may not have symptoms, but there have been reports of heterozygous patients experiencing symptoms.²

The symptoms of the disease include mental retardation, growth retardation, megaloblastic anemia, immunodeficiency, and high levels of orotic acid in the patient’s urine, approximately 500 to 1000 times the normal amount. Megaloblastic anemia does not respond and cannot be cured by administration of vitamin B₁₂ or folic acid.^2,3

Uridine treatment is effective because it can easily be converted into a usable form and then used by the body for RNA formation. Xuriden is available in single-use packets that contain oral granules and can be administered with milk, formula, or soft food such as applesauce, pudding, or yogurt.

The recommended dose is 60 mg/kg daily, which can be titrated to 120 mg/kg daily if needed (maximum of 8 g/day).

Reasons to increase the dose include:

• Orotic acid levels in the urine remain above normal or increase above the usual or expected range for the patient.
• Laboratory values affected by the disease show evidence of worsening.
• There is worsening of other signs/symptoms of the disease.

The package insert comes with a dosing chart and complete instructions on how to mix the medication with food or milk. The medication may be weighed out or administered by graduated teaspoons.

A pharmacist must remember to increase the dose as the patient grows and gains weight.

Currently, there are no reported drug interactions or known adverse reactions with Xuriden treatment. Still, health care professionals are encouraged to report any suspected interactions or adverse reactions.

References:

1. Brosnan ME, Brosnana JT. Orotic acid excretion and arginine metabolism. J Nutri. 2007;137(6 Suppl 2):1656S-1661S.

2. Imaeda M, Satoshi S, Imaeda H, et al. Hereditary orotic aciduria heterozygotes accompanied with neurological symptoms. Tohoku J Exp Med. 1998;185:67-70.

3. Debnath SK, Aggarwal A, Mittal H. Megaloblastic Anemia — A Rare Cause. Indian J Pediatr. 2011;78(10):1293-1295.

4. Xuriden (uridine triacetate) oral granules. Package insert. 9/2015.