Features include always present findings: Generalized hypotonia, Esophageal stenosis, Downturned corners of mouth, and Exodeviation and others; and very common findings: Intellectual disability and Achalasia. 32 total HPO annotations.

GMPPA encodes GDP-mannose pyrophosphorylase A (420 aa). Regulatory subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex; reduces the catalytic activity of GMPPB when part of the complex. Highest expression in Pituitary (78.8 TPM) and Cervix Endocervix (63.0 TPM).

Alacrima, achalasia, and intellectual disability syndrome is caused by mutations in the GMPPA gene on chromosome 2.

The GMPPA protein participates in GMPPB converts Mannose-1-phosphate to GDP-Mannose pathway.

GMPPA is classified as a druggable target (Enzyme category) with score 0.0.

Genetic testing for GMPPA is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 12 always present features, 2 very common features, 4 common features.

No clinical trials have been registered for alacrima, achalasia, and intellectual disability syndrome.

2 publications have been identified in PubMed for alacrima, achalasia, and intellectual disability syndrome. Research spans Review / Meta-Analysis (50%) and Case Report / Case Series (50%).

Recent Publications

• Altassan R (2025). [PMID: 40706141](https://pubmed.ncbi.nlm.nih.gov/40706141/). *Molecular genetics and metabolism*. [Review / Meta-Analysis]

• Smits DJ (2024). [PMID: 39003500](https://pubmed.ncbi.nlm.nih.gov/39003500/). *HGG advances*. [Case Report / Case Series]