Hyperphosphatasia-intellectual disability syndrome

Hyperphosphatasia-intellectual disability syndrome (HPID syndrome), also known as Mabry syndrome, is a rare autosomal recessive disorder characterized by elevated serum alkaline phosphatase (hyperphosphatasia) combined with intellectual disability and distinctive facial features. The condition is caused by mutations in genes involved in the glycosylphosphatidylinositol (GPI) anchor biosynthesis pathway, including PIGV, PIGO, PGAP2, PGAP3, and PIGL. GPI anchors are essential for tethering certain proteins to the cell surface, and defects in this pathway lead to the release of alkaline phosphatase into the bloodstream and impaired function of other GPI-anchored proteins critical for neurological development. The syndrome primarily affects the nervous system and skeletal system. Key clinical features include moderate to severe intellectual disability, seizures (often appearing in infancy or early childhood), delayed speech and motor development, and characteristic facial features such as a broad nasal bridge, widely spaced eyes (hypertelorism), a tented upper lip, and brachytelephalangy (shortened terminal phalanges of the fingers). Some patients may also exhibit hearing loss, hypotonia, and behavioral abnormalities. The persistent elevation of serum alkaline phosphatase is a hallmark laboratory finding that aids in diagnosis. There is currently no cure for hyperphosphatasia-intellectual disability syndrome. Treatment is supportive and symptomatic, focusing on seizure management with antiepileptic medications, early intervention programs including speech therapy, physical therapy, and occupational therapy to optimize developmental outcomes. Genetic counseling is recommended for affected families. Diagnosis is confirmed through biochemical testing showing elevated alkaline phosphatase and molecular genetic testing identifying pathogenic variants in the relevant GPI-anchor pathway genes.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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