USMLE (United States Medical Licensing Examination) Step 1 Practice Exam

What is the classic presentation of Hereditary Orotic Aciduria?

1. Hemolytic anemia

2. Iron overload

3. Megaloblastic anemia

4. Sickle cell anemia

The correct answer is: Megaloblastic anemia

Hereditary Orotic Aciduria is characterized by a deficiency in the enzyme orotate phosphoribosyl transferase (OPRT), which plays a critical role in the pyrimidine synthesis pathway. This deficiency leads to the accumulation of orotic acid in the urine and results in a decreased production of pyrimidines, particularly uridine. The lack of uridine ultimately impairs DNA and RNA synthesis, leading to ineffective erythropoiesis. The classic presentation of this condition includes megaloblastic anemia due to the inability to produce adequate levels of nucleotides that are necessary for proper cell division and maturation of red blood cells. In patients with megaloblastic anemia, there is an increase in the size of red blood cells (macrocytosis) that occurs as a result of delayed maturation in the bone marrow. Megaloblastic anemia due to pyrimidine deficiency is distinct from other types of anemia listed in the choices. For example, hemolytic anemia is caused by the destruction of red blood cells, iron overload relates to excess iron deposition (such as in hemochromatosis), and sickle cell anemia is a genetic disorder resulting from abnormal hemoglobin structure. These conditions do not primarily involve a defect