Bilateral Glaucoma as Possible Additional Feature for PGAP3-Associated Hyperphosphatasia.

Area of Science:

• Genetics
• Rare Diseases
• Pediatric Ophthalmology

Background:

• Hyperphosphatasia with mental disorder (HPMRS) is a rare autosomal recessive condition.
• It results from gene mutations affecting lipid synthesis and remodeling.
• HPMRS has diverse clinical manifestations.

Observation:

• A seven-month-old boy presented with bilateral glaucoma, cleft palate, facial dysmorphism, hypertelorism, a broad nasal bridge, and large earlobes.
• Brain MRI revealed abnormalities consistent with HPMRS type-4.
• This presentation is atypical for HPMRS.

Findings:

• Whole exome sequencing identified a homozygous pathogenic variant in the PGAP3 gene (c.320C>T, p.Ser107Leu).
• This genetic finding confirmed the diagnosis of HPMRS type-4.
• The study details an unusual phenotype for this rare disorder.

Implications:

• This case expands the known phenotypic spectrum of HPMRS type-4.
• It suggests that syndromic congenital glaucoma should be considered in the differential diagnosis of HPMRS.
• Highlights the importance of genetic testing in diagnosing rare pediatric conditions.