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 Weiss; Assaf Arie Barg; Ayman Daka; Ninette Amariglio; May Christine V. Malicdan; William A. Gahl; Yair Anikster

doi:10.1016/j.ymgme.2019.08.003

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

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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 language	English
Pages (from-to)	151-161
Number of pages	11
Journal	Molecular Genetics and Metabolism
Volume	128
Issue number	1-2
DOIs	https://doi.org/10.1016/j.ymgme.2019.08.003
State	Published - 1 Sep 2019
Externally published	Yes

Bibliographical note

Funding Information:
The authors wish to thank the patients and their families for their kind cooperation. This study was supported in part by funds from the Israel Science Foundation (grant number 2023/14 ) (G.H.); the Talpiot Medical Leadership Program (B.P.S., G.H., N.P.S.); and the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health.

Publisher Copyright:
© 2019

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ymgme.2019.08.003

Cite this

Pode-Shakked, B., Heimer, G., Vilboux, T., Marek-Yagel, D., Ben-Zeev, B., Davids, M., Ferreira, C. R., Philosoph, A. M., Veber, A., Pode-Shakked, N., Kenet, G., Soudack, M., Hoffmann, C., Vernitsky, H., Safaniev, M., Lodzki, M., Lahad, A., Shouval, D. S., Levinkopf, D., ... Anikster, Y. (2019). Cerebral and portal vein thrombosis, macrocephaly and atypical absence seizures in Glycosylphosphatidyl inositol deficiency due to a PIGM promoter mutation. Molecular Genetics and Metabolism, 128(1-2), 151-161. https://doi.org/10.1016/j.ymgme.2019.08.003

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

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.",

keywords = "Absence seizures, Congenital disorders of glycosylation, GPI, Glycosylphosphatidylinositol deficiency, PIGM, Portal vein thrombosis",

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

note = "Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = sep,

day = "1",

doi = "10.1016/j.ymgme.2019.08.003",

language = "אנגלית",

volume = "128",

pages = "151--161",

journal = "Molecular Genetics and Metabolism",

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Pode-Shakked, B, Heimer, G, Vilboux, T, Marek-Yagel, D, Ben-Zeev, B, Davids, M, Ferreira, CR, Philosoph, AM, Veber, A, Pode-Shakked, N, Kenet, G, Soudack, M, Hoffmann, C, Vernitsky, H, Safaniev, M, Lodzki, M, Lahad, A, Shouval, DS, Levinkopf, D, Weiss, B, Barg, AA, Daka, A, Amariglio, N, Malicdan, MCV, Gahl, WA & Anikster, Y 2019, 'Cerebral and portal vein thrombosis, macrocephaly and atypical absence seizures in Glycosylphosphatidyl inositol deficiency due to a PIGM promoter mutation', Molecular Genetics and Metabolism, vol. 128, no. 1-2, pp. 151-161. https://doi.org/10.1016/j.ymgme.2019.08.003

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T1 - Cerebral and portal vein thrombosis, macrocephaly and atypical absence seizures in Glycosylphosphatidyl inositol deficiency due to a PIGM promoter mutation

AU - Pode-Shakked, Ben

AU - Heimer, Gali

AU - Vilboux, Thierry

AU - Marek-Yagel, Dina

AU - Ben-Zeev, Bruria

AU - Davids, Mariska

AU - Ferreira, Carlos R.

AU - Philosoph, Amit Mary

AU - Veber, Alvit

AU - Pode-Shakked, Naomi

AU - Kenet, Gili

AU - Soudack, Michalle

AU - Hoffmann, Chen

AU - Vernitsky, Helly

AU - Safaniev, Marina

AU - Lodzki, Maya

AU - Lahad, Avishay

AU - Shouval, Dror S.

AU - Levinkopf, Dana

AU - Weiss, Batia

AU - Barg, Assaf Arie

AU - Daka, Ayman

AU - Amariglio, Ninette

AU - Malicdan, May Christine V.

AU - Gahl, William A.

AU - Anikster, Yair

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

KW - Absence seizures

KW - Congenital disorders of glycosylation

KW - GPI

KW - Glycosylphosphatidylinositol deficiency

KW - PIGM

KW - Portal vein thrombosis

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AN - SCOPUS:85070936452

SN - 1096-7192

VL - 128

SP - 151

EP - 161

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

IS - 1-2

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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