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Hyperprolinemia type 2 is an autosomal recessive proline metabolism disorder due to pyroline-5-carboxylate dehydrogenase deficiency. The condition is often benign but clinical signs may include seizures, intellectual deficit and mild developmental delay.
Features include always present findings: Reduced tissue delta-1-pyrroline-5-carboxylate dehydrogenase activity. 9 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Brain and nerves | 2 | Seizure, Intellectual disability |
Kidneys and urinary system | 1 | Elevated urinary pyrroline hydroxycarboxylic acid level |
Lab test results | 1 | Elevated circulating 1-pyrroline-5-carboxylic acid concentration |
ALDH4A1 encodes aldehyde dehydrogenase 4 family member A1 (563 aa). Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. Highest expression in Liver (268.2 TPM) and Kidney Cortex (150.6 TPM).
Hyperprolinemia type 2 is caused by mutations in the ALDH4A1 gene on chromosome 1.
The ALDH4A1 protein participates in ALDH4A1 oxidizes 1PYR-3OH-5COOH, ALDH4A1 oxidises L-GluSS to Glu, and ALDH4A1 converts 1PYR-3OH-5COOH to 4-OH-L-glutamate pathways.
ALDH4A1 is classified as a druggable target (Druggable Genome and Enzyme categories) with score 0.0.
Genetic testing for ALDH4A1 is available. Testing is considered confirmatory for diagnosis.
Phenotype severity distribution: 1 always present feature.
Estimated prevalence: Unknown (Unknown prevalence).
No clinical trials have been registered for hyperprolinemia type 2.
2 publications have been identified in PubMed for hyperprolinemia type 2. Research spans Review / Meta-Analysis (50%) and Case Report / Case Series (50%).
AlQurashi FO (2025). [PMID: 41602883](https://pubmed.ncbi.nlm.nih.gov/41602883/). *Front Pediatr*. [Case Report / Case Series]
Meng Z (2025). [PMID: 40383172](https://pubmed.ncbi.nlm.nih.gov/40383172/). *Pharmacol Res*. [Review / Meta-Analysis]
Data assembled from 7 of 12 sources · Last updated Sep 18, 2026, 3:27 AM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center