Summary about Disease
Deficiency of uridine monophosphate synthase (UMPS) is a rare autosomal recessive metabolic disorder affecting pyrimidine synthesis. UMPS is a bifunctional enzyme that catalyzes the last two steps in the de novo synthesis of pyrimidine nucleotides. This deficiency leads to an accumulation of orotic acid, causing orotic aciduria. The classic presentation includes megaloblastic anemia refractory to vitamin B12 and folic acid, and often orotic crystalluria. Severe neurological abnormalities can also occur.
Symptoms
Megaloblastic anemia (unresponsive to B12 and folic acid)
Orotic aciduria (excess orotic acid in urine)
Failure to thrive
Developmental delay
Intellectual disability
Seizures (in some cases)
Crystalluria (crystals in urine)
Feeding difficulties
Causes
Deficiency of UMPS is caused by mutations in the UMPS gene. This gene provides instructions for making the uridine monophosphate synthase enzyme. Mutations in this gene disrupt the normal function of the enzyme, leading to a buildup of orotic acid and a deficiency of pyrimidine nucleotides. It is inherited in an autosomal recessive manner, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Uridine supplementation: This is the primary treatment. Uridine is a pyrimidine nucleotide that bypasses the metabolic block caused by UMPS deficiency. Oral uridine triacetate is commonly used.
Supportive care: Treatment for anemia and other complications.
Is Communicable
No, deficiency of UMPS is not communicable. It is a genetic disorder caused by mutations in a gene.
Precautions
Genetic counseling for families with a history of the disorder.
Adherence to prescribed uridine supplementation.
Regular monitoring by a healthcare professional to assess treatment effectiveness and manage potential complications.
Avoidance of dehydration to reduce the risk of orotic acid crystal formation in the kidneys.
How long does an outbreak last?
This is not an infectious disease and therefore does not have "outbreaks." It is a chronic genetic condition requiring ongoing management. The symptoms persist unless treated.
How is it diagnosed?
Urine orotic acid analysis: Elevated orotic acid levels in the urine are a key diagnostic marker.
Blood tests: To evaluate for megaloblastic anemia.
Enzyme assay: Measuring UMPS enzyme activity in cells (e.g., fibroblasts or red blood cells).
Genetic testing: DNA sequencing of the UMPS gene to identify mutations.
Timeline of Symptoms
Symptoms typically manifest in infancy or early childhood. The exact timeline can vary depending on the severity of the deficiency and the individual. Anemia and failure to thrive are often the first symptoms noted. Neurological problems may develop later if the condition is untreated.
Important Considerations
Early diagnosis and treatment with uridine supplementation are crucial to improve outcomes and prevent long-term complications.
Dosage of uridine needs to be carefully monitored and adjusted by a medical professional based on individual response and tolerance.
Long-term follow-up is necessary to monitor for potential side effects of treatment and to address any ongoing medical needs.
Carrier testing is available for family members.