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An infant is identified on newborn screening with elevated proline levels. The child is clinically asymptomatic. Family history reveals the mother also has elevated proline on plasma amino acids but is healthy.
AR; PRODH (proline dehydrogenase / proline oxidase)
- Catalyzes the first step of proline catabolism (proline → pyrroline-5-carboxylate)
- PRODH is located at 22q11.21 (within the 22q11.2 deletion region)
- Hemizygous PRODH deletion in 22q11.2 deletion syndrome can cause mild hyperprolinemia
- Usually benign: most individuals are asymptomatic
- Elevated plasma proline (typically 5-10x upper limit of normal)
- May be detected incidentally on newborn screening or plasma amino acid analysis
- Some association with seizures and intellectual disability, but causality debated
- Much milder than hyperprolinemia type II (ALDH4A1, which has seizures and ID)
- Plasma amino acids: elevated proline
- Urine amino acids: prolinuria, hydroxyprolinuria, glycinuria (overflow)
- PRODH gene testing
- Consider 22q11.2 deletion testing if other features present
- Usually no treatment needed; most individuals are asymptomatic and require no dietary proline restriction
- Reassurance and genetic counseling for the benign biochemical phenotype
- Evaluate and manage any associated 22q11.2 deletion syndrome features if present
"PRO-DH = PROline DeHydrogenase": the gene name tells you the enzyme and substrate.
Type I vs Type II: Type I (PRODH) is usually benign. Type II (ALDH4A1) is more severe with seizures. Think "1 is fine, 2 is trouble."
22q11.2 connection: PRODH sits within the 22q11.2 deletion region, so patients with DiGeorge syndrome may have mild hyperprolinemia as a secondary finding.