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Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency is characterized by psychomotor delay and severe myopathy (hypotonia, absent tendon reflexes and delayed myelination) from birth, associated with hypermethioninaemia and elevated serum creatine kinase levels.
Data assembled from 8 of 12 sources · Last updated Sep 20, 2026, 9:37 PM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center
Features include always present findings: Hypermethioninemia, Poor head control, Elevated circulating aspartate aminotransferase concentration, and Global developmental delay and others. 18 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Lab test results | 4 | Elevated circulating aspartate aminotransferase concentration, Decreased tissue S-adenosylhomocysteine hydrolase activity, Increased circulating creatine kinase MM isoform |
Brain and nerves | 2 | Global developmental delay, Intellectual disability |
Muscles | 2 | Low muscle tone (hypotonia), Increased variability in muscle fiber diameter |
Growth and development | 1 | Failure to thrive |
Digestive system | 1 | Decreased hepatic echogenicity |
Head and neck | 1 | Abnormal facial shape |
Heart and blood vessels | 1 | Heart muscle disease (cardiomyopathy) |
AHCY encodes adenosylhomocysteinase (432 aa). Catalyzes the hydrolysis of S-adenosyl-L-homocysteine to form adenosine and homocysteine. Binds copper ions Highest expression in Ovary (179.4 TPM) and Cells EBV-transformed lymphocytes (163.2 TPM).
Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase is caused by mutations in the AHCY gene on chromosome 20.
The AHCY protein participates in p-6Y-FGFR2(22-767)-AHCYL1(108-530) fusion, FGFR2(22-767)-AHCYL1(108-530) fusion, and AHCY mutants:NAD+ pathways.
AHCY is classified as a druggable target (Druggable Genome and Enzyme categories) with score 0.0.
Genetic testing for AHCY is available. Testing is considered confirmatory for diagnosis.
Biomarker and diagnostic research for hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase has been reported in the published literature.
Phenotype severity distribution: 12 always present features.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
1 clinical trial registered, 1 recruiting. Interventions under study include other interventions and biologic therapy. Research is primarily sponsored by academic and government institutions.
9 publications have been identified in PubMed for hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase. Research spans Case Report / Case Series (44%), Review / Meta-Analysis (22%), and Basic Science / Preclinical (22%).
Huang XW (2026). [PMID: 41452423](https://pubmed.ncbi.nlm.nih.gov/41452423/). *World J Pediatr*. [Review / Meta-Analysis]
Liao K (2026). [PMID: 41549122](https://pubmed.ncbi.nlm.nih.gov/41549122/). *Cell Res*. [Basic Science / Preclinical]
Triono A (2026). [PMID: 41543614](https://pubmed.ncbi.nlm.nih.gov/41543614/). *Neurogenetics*. [Review / Meta-Analysis]
Zhang H (2025). [PMID: 40727585](https://pubmed.ncbi.nlm.nih.gov/40727585/). *Front Genet*. [Diagnostic / Biomarker]
Öz A (2025). [PMID: 39899686](https://pubmed.ncbi.nlm.nih.gov/39899686/). *J Pediatr Hematol Oncol*. [Case Report / Case Series]
Lipari Pinto P (2024). [PMID: 39512434](https://pubmed.ncbi.nlm.nih.gov/39512434/). *JIMD Rep*. [Case Report / Case Series]
Meine BM (2024). [PMID: 39236587](https://pubmed.ncbi.nlm.nih.gov/39236587/). *Biochem Biophys Res Commun*. [Basic Science / Preclinical]
Mu J (2024). [PMID: 39705457](https://pubmed.ncbi.nlm.nih.gov/39705457/). *Medicine (Baltimore)*. [Case Report / Case Series]
Ma X (2024). [PMID: 39511588](https://pubmed.ncbi.nlm.nih.gov/39511588/). *BMC Pediatr*. [Case Report / Case Series]