Hyperphosphatasia With Intellectual Disability (Mabry Syndrome) due to Compound Heterozygous PIGO Variants: First Molecularly Characterized Case in French Guiana: A Case Report and Review of the Literatu
Mody Diop, Joddy Mafema Missindu, Narcisse ElengaIntroduction
Hyperphosphatasia with intellectual disability syndrome (HPMRS), also known as Mabry syndrome, is a rare autosomal recessive disorder of glycosylphosphatidylinositol (GPI) anchor biosynthesis. Approximately 20 cases with pathogenic PIGO variants have been reported worldwide. This makes PIGO ‐related HPMRS one of the rarest molecularly defined subtypes of the disease.
Case Report
We report a male infant from French Guiana. He presented with neonatal tremors, global developmental delay with postural delay, and generalized tonic–clonic seizures with dystonic features. Symptoms began at 9 months and worsened by 13 months. Biochemical testing showed persistently elevated serum alkaline phosphatase (ALP 477 then 415 U/L; reference range 142–335 U/L). Trio whole‐exome sequencing identified two compound heterozygous PIGO variants: c.839T > C (p.Met280Thr), inherited from the father, and c.590C > T (p.Pro197Leu), inherited from the mother. The diagnostic laboratory classified both as probably pathogenic (Class 4). Physical examination at 17 months showed growth retardation (height and weight at −2 SD) and a reducible umbilical hernia. There was no notable facial dysmorphism or limb anomaly.
Conclusion
We report the first molecularly characterized case of PIGO ‐related HPMRS in French Guiana. The diagnosis combined clinical, biochemical, and molecular evaluation. This case shows that the PIGO phenotype extends beyond classic dysmorphic presentations.