AUTHOR=Pan Yijun , Ren Bin , Chen Lijuan , Li Qiang 

TITLE=A case report of PGAP2-related hyperphosphatasia with impaired intellectual development syndrome in a Chinese family and literature review

JOURNAL=Frontiers in Pediatrics

VOLUME=12

YEAR=2024

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2024.1419976

DOI=10.3389/fped.2024.1419976

ISSN=2296-2360

ABSTRACT=<p>Recently, mutations have been identified in six genes (<italic>PIGA</italic>, <italic>PIGY</italic>, <italic>PIGO</italic>, <italic>PGAP2</italic>, <italic>PIGW</italic> and <italic>PGAP3</italic>) encoding proteins in the Glycosyl phosphatidylinositol(GPI)-anchor-synthesis pathway in individuals with hyperphosphatasia with impaired intellectual development syndrome(HPMRS). Reports involving the rare pathogenic gene, post-GPI attachment to proteins 2 (<italic>PGAP2</italic>) are quite limited. In this study, we reported two patients with <italic>PGAP2</italic> variants related neurodevelopmental disorders from Asian population. The proband, onset of epileptic spasms at 5 months, concurrently with global developmental dalay, facial malformation and elevated alkaline phosphatase. His younger sister, onset of epileptic spasms at 2 months, having similar clinical features as the proband. Their phenotypes are consistent with <italic>PGAP2</italic> related diseases. The two missense variants [c.686C&gt;T (p.Ala229Val) and c.677C&gt;T (p.Thr226Ile)] in <italic>PGAP2</italic> gene found in this family were segregation with the disease, while c.677C&gt;T (p.Thr226Ile) was a novel variant. All the two patients showed a positive response to ACTH treatment and high-dose pyridoxine. In summary, this study contributes to expanding the pathogenic variant spectrum of <italic>PGAP2</italic> related HPMRS, and provides new insights into the treatment.</p>