[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Hereditary orotic aciduria

[Conditions](https://durgical.com/en/conditions/) · [Metabolism: purines and pyrimidines](https://durgical.com/en/conditions/)

# Hereditary orotic aciduria

A very rare inherited disease in which pyrimidines are not made properly: anaemia that does not improve with vitamins and crystals in the urine.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Kidneys](https://durgical.com/en/anatomy/kidney/)
- [Ureters](https://durgical.com/en/anatomy/ureter/)
- [Urinary bladder](https://durgical.com/en/anatomy/urinary-bladder/)
- [Renal pelvis](https://durgical.com/en/anatomy/renal-pelvis/)

## In biochemistry

- [Pyrimidine synthesis: Step 5 · UMP synthase: orotate phosphoribosyltransferase](https://durgical.com/en/biochemistry/pathways/pyrimidine-synthesis/#paso-5)
- [Pyrimidine synthesis: Step 6 · UMP synthase: OMP decarboxylase](https://durgical.com/en/biochemistry/pathways/pyrimidine-synthesis/#paso-6)
- [CAD (carbamoyl phosphate synthetase II)](https://durgical.com/en/biochemistry/enzymes/cad/)
- [UMP synthase](https://durgical.com/en/biochemistry/enzymes/ump-synthase/)
- [Orotic acid](https://durgical.com/en/biochemistry/molecules/orotic-acid/)

## What it is

Autosomal recessive UMP synthase deficiency that blocks pyrimidine synthesis: orotic acid builds up and a megaloblastic anaemia resistant to B12 and folate appears.

## Who gets it

Very rare: only a few dozen cases have been described worldwide. There are no Colombian data; it should be considered in an infant with megaloblastic anaemia that does not respond to vitamins.

## Causes

- Pathogenic variants in both copies of the UMPS gene (autosomal recessive inheritance)

## Risk factors

- Carrier parents or consanguinity

## Pathophysiology

UMP synthase joins orotate to PRPP (OPRT) and decarboxylates OMP to UMP (ODC). When it fails, UMP and therefore UTP, CTP and dTTP run short: rapidly dividing cells such as blood precursors cannot complete their DNA and become megaloblastic. With little UTP, CPS-II loses its brake and makes even more orotate, which is excreted in large amounts and can crystallise.

## Classification

- Type I: both activities (OPRT and ODC) are missing; the usual form
- Type II: only ODC is missing; exceptional

## Symptoms and signs

- Pallor and tiredness from megaloblastic anaemia from the first months
- Failure to thrive and developmental delay
- Crystals in the urine, sometimes with urinary obstruction
- Frequent infections in some patients

## Red flags

- Megaloblastic anaemia that does not improve with B12 and folic acid
- Reduced urine output or haematuria from crystals

## Diagnosis

**Clinical**
An infant with vitamin-resistant megaloblastic anaemia, failure to thrive and crystalluria.

**Tests**
Very high urinary orotic acid with normal blood ammonia (rules out OTC deficiency); blood count with macrocytosis and megaloblastic smear; normal B12 and folate; red cell UMP synthase activity and UMPS genetic testing.

**Imaging**
Renal and urinary tract ultrasound if crystal obstruction is suspected.

## Treatment

**Medical**
Lifelong oral uridine (as uridine triacetate): it supplies pyrimidines bypassing the enzyme and turns down orotate production

**Follow-up**
Regular monitoring of blood count, urinary orotic acid and growth

**Lifestyle**
Good hydration to reduce crystalluria

## Complications

- Urinary obstruction from orotic acid crystals
- Developmental delay if treatment starts late

## Prognosis

With early uridine, the anaemia corrects and growth usually normalises.

## Test yourself

Think of the answer, then tap the question to see it.

## Which enzyme fails in hereditary orotic aciduria?

UMP synthase (OPRT and ODC activities), which turns orotate into UMP.

## Which test separates it from OTC deficiency?

Blood ammonia: normal in hereditary orotic aciduria and high in OTC deficiency.

## Why does uridine correct the disease?

Uridine kinase turns it into UMP without UMP synthase, and the resulting UTP turns down CPS-II.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/conditions/hereditary-orotic-aciduria/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [UMPS: Uridine 5'-monophosphate synthase (human)](https://www.uniprot.org/uniprotkb/P11172/entry) (UniProt, 2026); [Pyrimidine biosynthesis](https://reactome.org/PathwayBrowser/#/R-HSA-500753) (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

[← All conditions](https://durgical.com/en/conditions/)

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/conditions/hereditary-orotic-aciduria/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/hereditary-orotic-aciduria/