Orotic aciduria can be diagnosed through genetic sequencing of the UMPS gene. Treatment Treatment is administration of uridine monophosphate (UMP) or uridine triacetate (which is converted to UMP). These medications will bypass the missing enzyme and provide the body with a source of pyrimidines
Pyrimidine
Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. One of the three diazines, it has the nitrogen atoms at positions 1 and 3 in the ring. The other diazines are pyrazine and pyridazine. In nucleic acids, three types of nucleobases are pyrimidine derivatives: cytosine…
What is the treatment for orotic aciduria?
Orotic aciduria can be diagnosed through genetic sequencing of the UMPS gene. Treatment is administration of uridine monophosphate (UMP) or uridine triacetate (which is converted to UMP). These medications will bypass the missing enzyme and provide the body with a source of pyrimidines.
What are the signs and symptoms of orotic aciduria?
Patients typically present with excessive orotic acid in the urine, failure to thrive, developmental delay, and megaloblastic anemia which cannot be cured by administration of vitamin B12 or folic acid. Orotic aciduria has an autosomal recessive mode of inheritance.
What is the prognosis of orotic aciduria?
In addition to the characteristic excessive orotic acid in the urine, patients typically have megaloblastic anemia (UMP synthase deficiency) which cannot be cured by administration of vitamin B12 or folic acid. Orotic aciduria can also cause inhibition of RNA and DNA synthesis and ultimately, failure to thrive.
What is orotic aciduria type 1?
Summary Summary. 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.
How does UMP and UTP treat orotic aciduria?
Treatment. Treatment is administration of uridine monophosphate (UMP) or uridine triacetate (which is converted to UMP). These medications will bypass the missing enzyme and provide the body with a source of pyrimidines.
What are the signs and symptoms of orotic aciduria?
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.
What is the enzyme defect in orotic aciduria?
The defective enzyme is uridine monophosphate synthase. The disease is caused by mutations in the UMPS gene, which encodes a protein with orotate phosphoribosyltransferase and orotidylic decarboxylase activity.
Why megaloblastic anemia occurs in orotic aciduria?
Orotic aciduria is associated with megaloblastic anemia due to decreased pyrimidine synthesis, which leads to decreased nucleotide-lipid cofactors needed for erythrocyte membrane synthesis in the bone marrow.
What is OTC disease?
Ornithine transcarbamylase (OTC) deficiency is a rare X-linked genetic disorder characterized by complete or partial lack of the enzyme ornithine transcarbamylase (OTC). OTC is one of six enzymes that play a role in the break down and removal of nitrogen the body, a process known as the urea cycle.
What causes high orotic acid?
In OTC deficiency, carbamoyl phosphate accumulates and is alternatively metabolized to orotic acid. Allopurinol inhibits orotidine monophosphate decarboxylase and, when given to OTC carriers (who may have normal orotic acid excretion), can cause increased excretion of orotic acid.
Why is type 1 orotic aciduria caused?
OA1 is caused by changes 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.
What is megaloblastic anemia?
Megaloblastic anemia is a type of anemia characterized by very large red blood cells. In addition to the cells being large, the inner contents of each cell are not completely developed. This malformation causes the bone marrow to produce fewer cells, and sometimes the cells die earlier than the 120-day life expectancy.
What is orotic aciduria type1?
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.[13805] It typically becomes apparent in the first months of life with megaloblastic anemia, as well as delays in physical and intellectual development.[13805][5139] ...
What is orotic aciduria?
Orotic aciduria is an error of pyrimidine metabolism manifested by retarded growth and development, and megaloblastic anemia unresponsive to vitamin B12 and folic acid. Musculoskeletal abnormalities, strabismus, and congenital heart disease can be associated. Several affected patients had lymphopenia and increased susceptibility to infection, including candidiasis, fatal varicella, and meningitis. Immune findings are variable, and include low T cell number, impaired delayed type hypersensitivity response, reduced T cell-mediated killing, and decreased IgG and IgA. 320,321 Other patients have normal immune function. 322 The defective enzyme is uridine monophosphate synthase. The disease is caused by mutations in the UMPS gene, which encodes a protein with orotate phosphoribosyltransferase and orotidylic decarboxylase activity.
What enzyme is responsible for orotic aciduria?
Hereditary orotic aciduria is caused by the deficiency of uridine monophosphate synthase (UMPS). UMPS is a bifunctional enzyme consisting of orotate phosphoribosyltransferase and orotidine-5-monophosphate decarboxylase. UMPS catalyzes conversion of orotate to uridine monophosphate. The initial presenting findings are macrocytic anemia that is refractory to folic acid and vitamin B12 treatment. If not diagnosed and properly treated, growth, and developmental delays ensue.43 Diagnostic biomarkers include urine orotic acid and orotidine.
What is orotate used for?
It can also stem from food additives such as zinc orotate and magnesium orotate, which are used for metal ion substitution therapy. Salvage of deoxycytidine is important in DNA repair.
How is uridine taken up?
Uridine is taken up effectively by a carrier-mediated concentrated transport process or by cotransport, by all human cells except erythrocytes.
Is orotic aciduria autosomal recessive?
Hereditary orotic aciduria is a rare autosomal recessive trait. In this disorder, both orotate phosphoribosyltransferase and orotidine-5′-monophosphate decarboxylase activities (reactions 5 and 6 in Figure 25.16) are markedly deficient. Recall that these activities occur on the polypeptide Pyr 5,6.
Can orotic acid cause hematuria?
In terms of phenotypic expression, crystals of orotic acid can cause urethral and ureteral obstruction resulting in hematuria and renal impairment. Neurologically, one can see physical and mental development impairment with or without anemia.
Is orotic aciduria normal at birth?
Patients with hereditary orotic aciduria appear normal at birth but present at a few weeks or months of age with lethargy and failure to thrive, which, untreated, will be followed by developmental delay. Moderate to severe hypochromic anemia is found, with reticulocytes in the normal to low range.
Why is orotic aciduria characterized by excessive excretion of orotic acid in urine?
Orotic aciduria is characterized by excessive excretion of orotic acid in urine because of the inability to convert orotic acid to UMP. It causes megaloblastic anemia and may be associated with mental and physical developmental delays.
What is the treatment for pyrimidine?
Treatment is administration of uridine monophosphate (UMP) or uridine triacetate (which is converted to UMP). These medications will bypass the missing enzyme and provide the body with a source of pyrimidines.
Is orotic aciduria a type 2 disease?
As of 1988, only one case of type II orotic aciduria had ever been reported. Orotic aciduria is associated with megaloblastic anemia due to decreased pyrimidine synthesis, which leads to decreased nucleotide-lipid cofactors needed for erythrocyte membrane synthesis in the bone marrow.
Is orotic aciduria autosomal recessive?
Orotic aciduria has an autosomal recessive mode of inheritance. This autosomal recessive disorder is caused by a deficiency in the enzyme UMPS, a bifunctional protein that includes the enzyme activities of OPRT and ODC. In one study of three patients, UMPS activity ranged from 2-7% of normal levels. Two types of orotic aciduria have been reported.
Can orotic acid be elevated?
Elevated urinary orotic acid levels can also arise secondary to blockage of the urea cycle, particularly in ornithine transcarbamylase deficiency (OTC deficiency). This can be distinguished from hereditary orotic aciduria by assessing blood ammonia levels and blood urea nitrogen (BUN). In OTC deficiency, hyperammonemia and decreased BUN are seen because the urea cycle is not functioning properly, but megaloblastic anemia will not occur because pyrimidine synthesis is not affected. In orotic aciduria, the urea cycle is not affected.
Why does orotic acid build up in the body?
One of these final two steps is to convert orotic acid into another chemical substance. Because of a variation in the UMPS gene, affected individuals have very low levels of the enzyme needed to break down orotic acid. This causes orotic acid to buildup in the body.
What is Xuriden a treatment for?
The disorder is caused by variations in the UMPS gene. In 2015, the U.S. Food and Drug Administration (FDA) approved a treatment called uridine triacetate (Xuriden ) for this disorder.
Can urea cause orotic acid?
Other conditions, namely the urea cycle disorders, can also cause elevated levels of orotic acid. However, these disorders also cause elevated levels of ammonia in the blood, while hereditary orotic aciduria does not. Most affected individuals have had their diagnosis confirmed through molecular genetic testing.
Can you have children with orotic aciduria?
Although only a small number of people have been diagnosed with hereditary orotic aciduria, some affected individuals who were treated have gone to school, gotten married, have had children, and have lived a relatively unaffected lifestyle.
Can orotic aciduria cause long term complications?
Researchers do not know whether hereditary orotic aciduria can cause long-term complications. Any additional treatment would be direct toward the specific symptoms that are present in each individual. Genetic counseling can be of benefit for affected individuals and their families.
What is an orotic acid?
What is Orotic Acid? Orotic acid, also known as pyrimidine carboxylic acid, is a heterocyclic compound. The acid was historically considered to be part of the vitamin B complex and was referred to as vitamin B13, but it was later discovered that it is not, in fact, a vitamin.
What is the role of orotic acid in the body?
Orotic acid plays a key role in the manufacture and maintenance of adenosine triphosphate (ATP) levels in the human body cells. Optimum levels of ATP are necessary in order to enhance the functioning of the heart.
What is the name of the acid that helps the heart produce ATP?
The heart requires high amounts of ATP, which can be assisted by orotic acid ( x ). Orotic Acid for Vitamin B12 or Cobalamin Deficiency. This deficiency is known as jaundice, which happens when a lack of vitamin B12 interferes with the production of red blood cells in the body.
What is the effect of orotic acid on athletes?
Orotic acid converts to beta-alanine, which is the precursor of anserine and carnosine. These are powerful “proton buffering agents” which delay fatigue and help boost endurance in athletes by preventing the buildup of lactic acid. Muscle Recovery and Sports Nutrition.
What is the richest source of orotic acid?
The richest dietary sources of orotic acid are organ meats like heart and liver, vegetables like carrots and beets, milk and other dairy products. It also comes in the form of a dietary supplement. Supplementing orotic acid can provide many direct and indirect medicinal and health benefits to the human body.
Does orotic acid help with muscle recovery?
Muscle Recovery and Sports Nutrition. Supplementing with orotic acid can help in overall muscle mass development. It is also important for athletes as it helps boost the uptake of glucose and the restoration of glycogen stores. On top of that, it even helps to enhance the uptake of creatine by the body muscles.
Can orotic acid cause nausea?
Despite the potential benefits of orotic acid there are some possible side effects to keep in mind ( x ). Nausea and intestinal upset can occur when taking this supplement. Loss of appetite is also possible. It may have a negative effect on one’s mood. Severe allergic reactions are rare.
Overview
Treatment
Treatment is administration of uridine monophosphate (UMP) or uridine triacetate (which is converted to UMP). These medications will bypass the missing enzyme and provide the body with a source of pyrimidines.
Signs and symptoms
Patients typically present with excessive orotic acid in the urine, failure to thrive, developmental delay, and megaloblastic anemia which cannot be cured by administration of vitamin B12 or folic acid.
Cause and genetics
This autosomal recessive disorder is caused by a deficiency in the enzyme UMPS, a bifunctional protein that includes the enzyme activities of OPRT and ODC. In one study of three patients, UMPS activity ranged from 2-7% of normal levels.
Two types of orotic aciduria have been reported. Type I has a severe deficiency of both activities of UMP synthase. In Type II orotic aciduria, the ODC activity i…
Diagnosis
Elevated urinary orotic acid levels can also arise secondary to blockage of the urea cycle, particularly in ornithine transcarbamylase deficiency (OTC deficiency). This can be distinguished from hereditary orotic aciduria by assessing blood ammonia levels and blood urea nitrogen (BUN). In OTC deficiency, hyperammonemia and decreased BUN are seen because the urea cycle is not functioning properly, but megaloblastic anemia will not occur because pyrimidine synthesis is n…