Hirschsprung's disease and a rare mutation of the PIGO gene: Mabry syndrome.

BACKGROUND: Mabry syndrome is a very rare condition characterized by cognitive impairment, distinctive facial features, hypotonia, elevated alkaline phosphatase (ALP) levels in the blood (hyperphosphatasia), and recurrent generalized tonic-clonic seizures. It can be accompanied by gastrointestinal anomalies such as Hirschsprung's disease (HD). In this study, we aim to present a case of hyperphosphatasia with impaired intellectual development syndrome 2 (HPMRS2) from Türkiye, featuring a novel homozygous p.Arg445Pro variant in the PIGO gene, occurring in association with HD. CASE PRESENTATION: A two-year-old male patient was referred to the pediatric neurology clinic with decreased responsiveness to the environment, lack of trunk control, and failure to respond to his name. ALP value was 613 IU/L. No pathology was detected in metabolic tests, vitamin D levels, or cranial magnetic resonance imaging, and electroencephalography (EEG). At 11 months of age, he had a generalized tonic-clonic seizure without fever. Since no abnormalities were detected in chromosome analysis and array analysis, whole exome sequencing (WES) was performed. A homozygous mutation was detected in the PIGO gene (NM_032634.4): c.1334G>C (p.Arg445Pro). Sanger analysis revealed heterozygous carrier status in both parents. The patient had constipation that was unresponsive to medical treatment since birth. Physical examination revealed abdominal distension. Rectal examination revealed an explosive discharge of gas and stool. A rectal biopsy was performed. The pathology result was ganglion-negative, and the patient was diagnosed with HD. After definitive surgery, spontaneous defecation has been achieved during follow-up, except for rare episodes of enterocolitis. CONCLUSIONS: It should be remembered that Mabry syndrome can be accompanied by gastrointestinal anomalies, primarily HD. This case highlights the increased phenotypic variability associated with PIGO mutations and demonstrates the importance of genetic assessment in atypical neurodevelopmental conditions.