TY - JOUR
T1 - Deciphering the premature mortality in PIGA-CDG
T2 - An untold story
AU - Bayat, Allan
AU - Kløvgaard, Marius
AU - Johannesen, Katrine M.
AU - Stefan Barakat, Tahsin
AU - Kievit, Anneke
AU - Montomoli, Martino
AU - Parrini, Elena
AU - Pietrafusa, Nicola
AU - Schelhaas, Jurgen
AU - van Slegtenhorst, Marjon
AU - Miya, Kazushi
AU - Guerrini, Renzo
AU - Tranebjærg, Lisbeth
AU - Tümer, Zeynep
AU - Rubboli, Guido
AU - Møller, Rikke S.
N1 - Funding Information:
The authors would like to thank the patients and their families for their participation in our research, especially when facing such a devastating issue as the death of their loved one. T.S.B. received financial support obtained from the Netherlands Organisation for Scientific Research (ZONMW VENI grant 9161702 ) and from a NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation.
Publisher Copyright:
© 2020 Elsevier B.V.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Objective: Congenital disorder of glycosylation (CDG) due to a defective phosphatidylinositol glycan anchor biosynthesis class A protein (PIGA) is a severe X-linked developmental and epileptic encephalopathy. Seizures are often treatment refractory, and patients have intellectual disability and global developmental delay. Previous reports have suggested that patients with PIGA-CDG have a high risk of premature mortality. This study aimed to evaluate the observed high mortality and the causes of death in PIGA-CDG patients. Methods: We reviewed the literature and collected additional unpublished patients through an international network. Results: In total, we reviewed the data of 88 patients of whom 30 patients born alive were deceased, and the overall mortality before the age of 20 years was 30 % (26/88). Age at death ranged from 15 days to 48 years of life. The median age at death was two years and more than half of the patients deceased in early childhood. The PIGA-specific mortality rate/1000 person-years was 44.9/1000 person-years (95 %, CI 31.4–64.3). There were no cases of definite or probable sudden unexpected death in epilepsy (SUDEP) and half of the patients died due to respiratory failure (15/30, 50 %) or possible SUDEP (3/30, 10 %). Three patients (10 %) died from severe cardiomyopathy, liver failure and gastrointestinal bleeding, respectively. The cause of death was unclassified in nine patients (30 %). Autopsies were rarely performed and the true cause of death remains unknown for the majority of patients. Significance: Our data indicate an increased risk of premature death in patients with PIGA-CDG when compared to most monogenic developmental and epileptic encephalopathies.
AB - Objective: Congenital disorder of glycosylation (CDG) due to a defective phosphatidylinositol glycan anchor biosynthesis class A protein (PIGA) is a severe X-linked developmental and epileptic encephalopathy. Seizures are often treatment refractory, and patients have intellectual disability and global developmental delay. Previous reports have suggested that patients with PIGA-CDG have a high risk of premature mortality. This study aimed to evaluate the observed high mortality and the causes of death in PIGA-CDG patients. Methods: We reviewed the literature and collected additional unpublished patients through an international network. Results: In total, we reviewed the data of 88 patients of whom 30 patients born alive were deceased, and the overall mortality before the age of 20 years was 30 % (26/88). Age at death ranged from 15 days to 48 years of life. The median age at death was two years and more than half of the patients deceased in early childhood. The PIGA-specific mortality rate/1000 person-years was 44.9/1000 person-years (95 %, CI 31.4–64.3). There were no cases of definite or probable sudden unexpected death in epilepsy (SUDEP) and half of the patients died due to respiratory failure (15/30, 50 %) or possible SUDEP (3/30, 10 %). Three patients (10 %) died from severe cardiomyopathy, liver failure and gastrointestinal bleeding, respectively. The cause of death was unclassified in nine patients (30 %). Autopsies were rarely performed and the true cause of death remains unknown for the majority of patients. Significance: Our data indicate an increased risk of premature death in patients with PIGA-CDG when compared to most monogenic developmental and epileptic encephalopathies.
KW - Cardiomyopathy
KW - Early cardiopulmonary death
KW - Early infantile epileptic encephalopathy
KW - Glycosylphosphatidylinositol biosynthesis defects
KW - Mortality
KW - PIGA
KW - SUDEP
U2 - 10.1016/j.eplepsyres.2020.106530
DO - 10.1016/j.eplepsyres.2020.106530
M3 - Journal article
C2 - 33508693
AN - SCOPUS:85099969537
VL - 170
JO - Epilepsy Research
JF - Epilepsy Research
SN - 0920-1211
M1 - 106530
ER -