A Novel PGAP3 Gene Mutation-Related Megalocornea Can Be Misdiagnosed as Primary Congenital Glaucoma
Abdulmajeed I Alhaidari1, Amani S Albakri2, Suzan S Alhumaidi3
1Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh, SAU.
Abstract:
Hyperphosphatasia with mental retardation syndrome 4 (HPMRS4) is a rare autosomal recessive disorder caused by glycosylphosphatidylinositol (GPI) deficiency. GPI deficiency results from a mutation in one of six known genes. Mutation in post-GPI attachment to protein phospholipase 3 gene (PGAP3) is linked to HPMRS4. Patients usually present with dysmorphic features, developmental delay, central hypotonia, and seizure. However, in our case, we report a novel homozygous missense mutation of PGAP3 gene in a female child who presented with megalocornea, which is an unusual clinical presentation for HPMRS4. Megalocornea, in her first days of life, led to a misdiagnosis of primary congenital glaucoma. Later, other common clinical features of HPMRS4 became apparent.
Insights
A novel mutation in the PGAP3 gene causes Hyperphosphatasia with mental retardation syndrome 4 (HPMRS4), a disorder linked to glycosylphosphatidylinositol (GPI) deficiency. This case highlights megalocornea as an unusual early symptom, potentially leading to misdiagnosis.
Area of Science:
- Genetics
- Biochemistry
- Pediatrics
Background:
- Hyperphosphatasia with mental retardation syndrome 4 (HPMRS4) is a rare autosomal recessive disorder.
- It is caused by a deficiency in glycosylphosphatidylinositol (GPI) anchor synthesis.
- Mutations in the PGAP3 gene are a known cause of HPMRS4.
Observation:
- A female infant presented with megalocornea, initially misdiagnosed as congenital glaucoma.
- This patient had a novel homozygous missense mutation in the PGAP3 gene.
- Later, typical clinical features of HPMRS4 manifested.
Findings:
- Identified a new homozygous missense mutation in the PGAP3 gene.
- Demonstrated an unusual presentation of HPMRS4 with megalocornea as a primary feature.
- Confirmed the association between PGAP3 mutations and GPI deficiency.
Implications:
- Expands the clinical spectrum of HPMRS4.
- Highlights the importance of considering genetic disorders in cases of unexplained megalocornea.
- Suggests PGAP3 mutations should be investigated in patients with GPI deficiency and neurological or developmental issues.
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