Two Different Brain Injury Patterns Associated with Compound Heterozygosis of the PIGO Gene in a Term Newborn: A Case...

The glycosylphosphatidylinositol (GPI) is a glycol-lipid that anchors several proteins to the cell surface. The GPI-anchor pathway is crucial for the correct function of proteins involved in cell function, and it is fundamental in early neurogenesis and neural development. The PIG gene family is a group of genes involved in this pathway with six genes identified so far, and defects in these genes are associated with a rare inborn metabolic disorder manifesting with a spectrum of clinical phenotypes in newborns and children. Among them, the PIGO gene encodes for phosphatidylinositol glycan anchor biosynthesis class O protein (PIGO), an enzyme participating in this cascade, and the loss of its function often leads to a severe clinical picture characterized by global developmental delay, seizures, Hirschsprung disease, and other congenital malformations. To date, 19 patients with confirmed PIGO deficiency have been described in the literature with a host of clinical and radiological manifestations. We report a case of a male term newborn with two compound heterozygous variants of the PIGO genes, presenting with encephalopathy, drug-resistant epilepsy, and gastrointestinal abnormalities. Brain MRI first showed diffusion restriction in the ponto-medullary tegmentum, ventral mesencephalon, superior cerebellar peduncles, cerebral peduncles, and globi pallidi. This pattern of lesion distribution has been described as part of the neuroradiological spectrum of PIG genes-related disorders. However, after one month of life, he also showed a previously undescribed MRI pattern characterized by extensive cortical and subcortical involvement of the brain hemispheres. The presence of two different mutations in both the PIGO genes may have been responsible for the particularly severe clinical picture and worse outcome, leading to the death of the newborn in the sixth month of life despite therapeutic attempts. This case expands the neuroradiological spectrum and may bring new insights on glycosylation-related disorders brain manifestations.