Hyperphosphatasia with mental retardation syndrome

Hyperphosphatasia with Mental Retardation Syndrome (HPMRS), also known as Mabry Syndrome, is a rare genetic disorder characterized by elevated levels of alkaline phosphatase in the blood, intellectual disability, and distinct facial features. The syndrome is caused by mutations in multiple genes, including PIGV, PGAP2, PGAP3, and PIGO, which are involved in the post-translational modification of proteins through glycosylphosphatidylinositol (GPI) anchoring. This condition falls under the broader category of GPI anchor biosynthesis disorders.

Symptoms and Characteristics

Individuals with HPMRS present a range of clinical features, including but not limited to:

• Intellectual Disability: Varying degrees of cognitive impairment are observed.
• Elevated Alkaline Phosphatase: Significantly high levels of alkaline phosphatase in the blood.
• Distinct Facial Features: These may include a broad nasal bridge, wide-set eyes, and a thin upper lip.
• Seizures: A proportion of affected individuals experience seizures.
• Growth Delay: Both pre- and postnatal growth retardation may be observed.
• Skeletal Anomalies: Such as brachycephaly (short skull) and other bone abnormalities.

Genetics

HPMRS is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the syndrome. The genes implicated in HPMRS, including PIGV, PGAP2, PGAP3, and PIGO, play crucial roles in the synthesis of GPI anchors. GPI anchors are glycolipids that tether certain types of proteins to the cell membrane. Mutations in these genes disrupt the normal function of GPI-anchored proteins, leading to the symptoms observed in HPMRS.

Diagnosis

Diagnosis of HPMRS is based on clinical evaluation, biochemical tests showing elevated alkaline phosphatase levels, and genetic testing confirming mutations in the associated genes. Due to the rarity of the condition and the variability of symptoms, HPMRS can be challenging to diagnose.

Treatment and Management

There is no cure for HPMRS, and treatment is symptomatic and supportive. Management strategies may include:

• Educational Support: Tailored educational programs to address intellectual disabilities.
• Medical Management: Treatment of seizures and other medical issues as they arise.
• Therapeutic Interventions: Physical, occupational, and speech therapies to support development and improve quality of life.

Prognosis

The prognosis for individuals with HPMRS varies depending on the severity of symptoms. While the syndrome does not typically affect life expectancy, the quality of life can be significantly impacted by intellectual disability and health complications.

See Also

• Genetic disorder
• Intellectual disability
• Alkaline phosphatase
• Glycosylphosphatidylinositol (GPI) anchor biosynthesis