## Ornithine Transcarbamylase (OTC) Deficiency **Key Point:** OTC deficiency is the most common urea cycle disorder. Because the enzyme cannot convert carbamoyl ammonia + ornithine → citrulline, carbamoyl ammonia accumulates and is shunted into alternative pathways, producing orotate (excreted as orotic acid in urine—a diagnostic hallmark). **High-Yield:** The characteristic biochemical pattern in OTC deficiency: - **Elevated citrulline** (because upstream substrate accumulates and is converted back to citrulline via salvage pathways) - **Normal or LOW arginine** (because citrulline cannot be converted to arginine downstream) - **Elevated ammonia** (hyperammonemia) - **Massive orotic acid in urine** (100–1000× normal) ### Urea Cycle Defects: Biochemical Patterns | Enzyme Deficiency | Elevated Amino Acids | Decreased Amino Acids | Urine Finding | Inheritance | |---|---|---|---|---| | CPS I | Glutamine, alanine | Citrulline, arginine | Normal | AR | | OTC | **Citrulline, ammonia** | **Arginine** | **Orotic acid ↑↑↑** | **X-linked** | | Argininosuccinate synthetase | Citrulline, ammonia | Arginine | Normal | AR | | Argininosuccinate lyase | Argininosuccinate, ammonia | Arginine | Argininosuccinate ↑ | AR | | Arginase | Arginine, ammonia | — | — | AR | **Mnemonic:** **OTC = Ornithine blocked → Citrulline accumulates, arginine drops, Orotic acid floods urine** **Clinical Pearl:** OTC deficiency is X-linked dominant (lethal in hemizygous males); heterozygous females present with variable hyperammonemia, often triggered by protein intake or infection. The massive orotic acid crystalluria is pathognomonic. 
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