Cerebral and portal vein thrombosis, macrocephaly and atypical absence seizures in Glycosylphosphatidyl inositol deficiency due to a PIGM promoter mutation

Ben Pode-Shakked, Gali Heimer, Thierry Vilboux, Dina Marek-Yagel, Bruria Ben-Zeev, Mariska Davids, Carlos R. Ferreira, Amit Mary Philosoph, Alvit Veber, Naomi Pode-Shakked, Gili Kenet, Michalle Soudack, Chen Hoffmann, Helly Vernitsky, Marina Safaniev, Maya Lodzki, Avishay Lahad, Dror S. Shouval, Dana Levinkopf, Batia WeissAssaf Arie Barg, Ayman Daka, Ninette Amariglio, May Christine V. Malicdan, William A. Gahl*, Yair Anikster

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Defects of the glycosylphosphatidylinositol (GPI) biosynthesis pathway constitute an emerging subgroup of congenital disorders of glycosylation with heterogeneous phenotypes. A mutation in the promoter of PIGM, resulting in a syndrome with portal vein thrombosis and persistent absence seizures, was previously described in three patients. We now report four additional patients in two unrelated families, with further clinical, biochemical and molecular delineation of this unique entity. We also describe the first prenatal diagnosis of PIGM deficiency, allowing characterization of the natural history of the disease from birth. The patients described herein expand the phenotypic spectrum of PIGM deficiency to include macrocephaly and infantile-onset cerebrovascular thrombotic events. Finally, we offer insights regarding targeted treatment of this rare disorder with sodium phenylbutyrate.

Original languageEnglish
Pages (from-to)151-161
Number of pages11
JournalMolecular Genetics and Metabolism
Volume128
Issue number1-2
DOIs
StatePublished - 1 Sep 2019

Funding

FundersFunder number
Talpiot Medical Leadership Program
National Institutes of Health
National Human Genome Research Institute
Israel Science Foundation2023/14

    Keywords

    • Absence seizures
    • Congenital disorders of glycosylation
    • GPI
    • Glycosylphosphatidylinositol deficiency
    • PIGM
    • Portal vein thrombosis

    Fingerprint

    Dive into the research topics of 'Cerebral and portal vein thrombosis, macrocephaly and atypical absence seizures in Glycosylphosphatidyl inositol deficiency due to a PIGM promoter mutation'. Together they form a unique fingerprint.

    Cite this