A Case Report of Hyperphosphatasia with Mental Retardation: Challenges of Differential Diagnosis

Hyperphosphatasia with mental retardation represents an extremely rare group of autosomal recessive metabolic disorders of glycosylation caused by glycosylphosphatidylinositol biosynthesis defect. Hyperphosphatasia is characterized by psychomotor development delay, seizures, variable congenital malformations, and a typical phenotype. A distinctive feature is a consistently elevated serum alkaline phosphatase level. We present a case of an 8-month-old boy with psychomotor retardation and multiple congenital malformations: Hirschsprung’s disease, bilateral obstructive megaureter with ureteral ectopia, and cryptorchidism. Diffuse muscular hypotonia, brachytelephalangy, and a characteristic facial phenotype were noted on examination. The maximum increase in the level of alkaline phosphatase was 1900 U/l. The differential diagnosis was carried out with microdeletion syndromes and Mowat‒Wilson syndrome. According to the results of whole exome sequencing with segregation analysis of the PIGV gene (NM_017837.4), the previously described pathogenic variant c.1022C>A (p.Ala341Glu) and the previously undescribed variant c.103_110del (p.Asp35Cysfs*32) were identified in the trans-configuration. Hyperphosphatasia with mental retardation, type 1, was diagnosed. The data obtained allows to expand knowledge about the phenotypic spectrum and differential diagnosis of hyperphosphatasia, which helps to verify the diagnosis and prevent birth of affected children.
Contribution: Kondakova O.B., Savostyanov K.V., Dyakonova E.Yu. — study concept definition of treatment tactics, manuscript editing; Gudkova A.P., Grebenkin D.I., Demyanov S.V., Davydova Yu.I., Tarzyan A.O., Pushkov A.A. — collection and processing, treatment manuscript writing. All co-authors approved the final version of the article and are responsible for the integrity of all parts of the article.
Acknowledgments. The study had no sponsorship.
Conflict of interest. The authors declare no conflict of interest.

Received: December 10, 2025
Accepted: March 20, 2026
Published: March 27, 2026

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