Hereditary orotic aciduria without megaloblastic anaemia

Other Names: Orotic aciduria type 1;Orotidylic pyrophosphorylase and orotidylic decarboxylase deficiency; UMPS deficiency; Uridine monophosphate synthase deficiency; UMP synthtase deficiency; Orotate phosphoribosyltransferase and omp decarboxylase deficiency; UMPS; Uridine monophosphate synthetase deficiency; Hereditary orotic aciduria; Orotic aciduria II (formerly); Oroticaciduria 1

Orotic aciduria type I (OA1), also known as hereditary orotic aciduria, is a rare condition characterized by elevated levels of orotic acid in the urine. It typically becomes apparent in the first months of life with megaloblastic anemia, as well as delays in physical and intellectual development.

OA1 differs from other causes of orotic aciduria, which may include mitochondrial disorders, lysinuric protein intolerance, and liver disease.

Cause

OA1 is caused by changes (mutations) in the UMPS gene and inheritance is autosomal recessive. OA1 differs from other causes of orotic aciduria, which may include mitochondrial disorders, lysinuric protein intolerance, and liver disease.

Inheritance

Autosomal recessive inheritance, a 25% chance

OA1 is inherited in an autosomal recessive pattern.

Symptoms

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Aminoaciduria(High urine amino acid levels)
• Anemia(Low number of red blood cells or hemoglobin)
• Global developmental delay
• Orotic acid crystalluria
• Oroticaciduria(High urine orotic acid levels)

30%-79% of people have these symptoms

• Abnormal toenail morphology(Abnormality of the toenail)
• Abnormality of the ureter
• Downslanted palpebral fissures(Downward slanting of the opening between the eyelids)
• Hip dysplasia
• Hypertelorism(Wide-set eyes)
• Impaired T cell function(T-cell dysfunction)
• Low-set, posteriorly rotated ears
• Patent ductus arteriosus
• Recurrent respiratory infections(Frequent respiratory infections)
• Splenomegaly(Increased spleen size)
• Wide nasal bridge(Broad nasal bridge)

5%-29% of people have these symptoms

• Atrial septal defect(An opening in the wall separating the top two chambers of the heart)
• Failure to thrive(Faltering weight)
• Ventricular septal defect(Hole in heart wall separating two lower heart chambers)

Diagnosis

Orotic aciduria type I (OA1) is diagnosed by a urine test that reveals very high amounts of orotic acid, with milder elevations of orotidine. The respective amounts of these substances result in an OA/orotidine ratio of above 10.Genetic testing of the UMPS gene is also available. A correct and timely diagnosis of OA1 is key to effective treatment for the condition.

Treatment

Treatment involves taking uridine; uridine triacetate was granted FDA approval for treating OA1 in 2015.Without treatment, children with OA1 may experience neutropenia, failure to thrive, developmental delay, and intellectual disability. The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Uridine triacetate (Brand name: Xuriden) Treatment of hereditary orotic aciduria.