Hereditary orotic aciduria type I is a rare autosomal recessive metabolic disorder characterized by a deficiency in the enzyme uridine monophosphate synthase (UMPS). This condition affects pyrimidine biosynthesis, resulting in excessive excretion of orotic acid in the urine and impaired growth and development.
Causes and Genetic Basis
Hereditary orotic aciduria type I is caused by mutations in the UMPS gene located on chromosome 3. This gene encodes a bifunctional enzyme that catalyzes two crucial reactions in pyrimidine nucleotide synthesis:
- Orotate phosphoribosyltransferase (OPRTase) activity
- Orotidine-5′-phosphate decarboxylase (OMP decarboxylase) activity
Mutations in UMPS lead to defective pyrimidine synthesis, causing orotic acid accumulation.
Symptoms of Hereditary Orotic Aciduria Type I
Common symptoms include:
- Failure to thrive
- Megaloblastic anemia (unresponsive to vitamin B12 or folic acid)
- Developmental delay
- Frequent infections
- Growth retardation
- Urinary crystals caused by excessive orotic acid excretion
Diagnosis
Diagnostic methods involve:
- Urine Analysis: Elevated orotic acid levels
- Blood Tests: Signs of megaloblastic anemia
- Genetic Testing: Identification of UMPS gene mutations
Treatment and Management
The primary treatment for hereditary orotic aciduria type I is oral uridine supplementation. Uridine bypasses the defective enzyme pathway, reducing orotic acid accumulation and improving symptoms.
Key Treatment Approaches:
- Uridine Triacetate: Effective in reducing orotic acid excretion and correcting anemia
- Folic Acid and Vitamin B12: Supportive treatment for improved red blood cell production
- Regular Monitoring: Orotic acid levels and blood counts should be routinely assessed
Prognosis
With early diagnosis and appropriate treatment, patients with hereditary orotic aciduria type I can achieve normal growth and development. However, untreated cases may lead to severe intellectual impairment and stunted growth.
Related Conditions
- Hereditary Orotic Aciduria Type II: A milder form with partial UMPS deficiency
- Ornithine Transcarbamylase (OTC) Deficiency: Also presents with elevated orotic acid but requires different management
Hereditary orotic aciduria type I is a rare yet manageable metabolic disorder. Timely diagnosis, genetic counseling, and appropriate treatment with uridine supplementation significantly improve patient outcomes.
FAQs
Q1: What causes hereditary orotic aciduria type I?
A: It results from mutations in the UMPS gene, impairing pyrimidine biosynthesis.
Q2: How is hereditary orotic aciduria type I diagnosed?
A: Diagnosis involves urine analysis for elevated orotic acid, blood tests for anemia, and genetic testing for UMPS mutations.
Q3: What is the treatment for hereditary orotic aciduria type I?
A: Uridine supplementation is the primary treatment, effectively reducing symptoms and improving growth.
Q4: Can hereditary orotic aciduria type I be cured?
A: While there is no permanent cure, uridine supplementation significantly improves the condition.
Q5: Is hereditary orotic aciduria type I fatal?
A: Without treatment, severe complications may arise, but with proper management, patients can lead healthy lives.
