2 case reports and literature review of hyperphosphatasia with mental retardation syndrome 2 caused by PIGO mutation

Xinyi Wang¹Jingya Zhao¹Xiaoke Zhao¹Le Ding²Yang Li^2*Min Zhu^1*

• ¹Department of Rehabilitation, Children's Hospital of Nanjing Medical University, Nanjing, China
• ²Department of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, China

Objective: This study investigates the clinical features and genetic mutations associated with hyperphosphatasia with impaired intellectual development syndrome-2 (HPMRS2). Methods: A retrospective analysis was performed on two HPMRS2 cases treated at the Department of Rehabilitation, Nanjing Children's Hospital, from 2019 to 2023. Clinical features and genetic characteristics were summarized through a literature review. Results: Genetic testing showed compound heterozygous variations in the PIGO gene for both patients (Patient c.[2612A>C];[2361dup]; Patient 2: c.[2510T>A];[693C>G]), with c.[2510T>A] and c.[693C>G] identified as novel mutations. Conclusion: Global developmental delay, with or without hyperphosphatemia, may indicate HPMRS2. The level of alkaline phosphatase elevation could reflect disease severity and prognosis. Our cases expand the known pathogenic variations in the PIGO gene and phenotypic spectrum of HPMRS2.