A deficiency of argininosuccinate lyase results in accumulation of which intermediate in the urea cycle?

Explanation

## Argininosuccinate Lyase Deficiency **Key Point:** Argininosuccinate lyase (step 4 of urea cycle) cleaves argininosuccinate into arginine and fumarate. When deficient, argininosuccinate accumulates proximal to the enzymatic block, while arginine and downstream products are depleted. **High-Yield:** Argininosuccinate lyase deficiency is the second most common urea cycle disorder after OTC deficiency. Patients present with hyperammonemia, developmental delay, seizures, and characteristic "trichomegaly" (abnormally long eyelashes). **Clinical Pearl:** Argininosuccinate is excreted in urine, giving a distinctive "fruity" odor. Plasma argininosuccinate levels are markedly elevated. ### Urea Cycle Blockade Pattern ```mermaid flowchart TD A["Carbamoyl-PO₄ + Ornithine<br/>CPS I, OTC"]:::action --> B["Citrulline<br/>Normal or ↑"]:::outcome B --> C["Citrulline + Aspartate<br/>Argininosuccinate synthetase"]:::action --> D["Argininosuccinate<br/>ACCUMULATES ↑↑↑"]:::urgent D --> E["Argininosuccinate lyase<br/>DEFICIENT ✗"]:::urgent E --> F["Arginine + Fumarate<br/>DEPLETED ↓"]:::outcome F --> G["Urea<br/>↓↓"]:::outcome ``` **Mnemonic:** **A**rgininosuccinate **L**yase → **A**rgininosuccinate **A**ccumulates (AL → AA) ### Comparison of Urea Cycle Defects | Enzyme Deficiency | Accumulated Substrate | Depleted Product | Urine Finding | Frequency | |---|---|---|---|---| | CPS I | Ammonia | Carbamoyl-PO₄ | None specific | Rare | | OTC | Carbamoyl-PO₄, Ammonia | Citrulline | Orotic acid ↑ | Most common (~50%) | | Argininosuccinate synthetase | Citrulline | Argininosuccinate | Citrulline ↑ | Rare | | **Argininosuccinate lyase** | **Argininosuccinate** | **Arginine** | **Argininosuccinate ↑** | **Second most common (~10%)** | | Arginase | Arginine | Urea | Arginine ↑ | Rare |