AUTHOR=Paprocka Justyna , Hutny Michał , Hofman Jagoda , Tokarska Agnieszka , Kłaniewska Magdalena , Szczałuba Krzysztof , Stembalska Agnieszka , Jezela-Stanek Aleksandra , Śmigiel Robert 

TITLE=Spectrum of Neurological Symptoms in Glycosylphosphatidylinositol Biosynthesis Defects: Systematic Review

JOURNAL=Frontiers in Neurology

VOLUME=Volume 12 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.758899

DOI=10.3389/fneur.2021.758899

ISSN=1664-2295

ABSTRACT=Background
Mutations of genes involved in synthesis of glycosylphosphatidylinositol and glycosylphosphatidylinositol-anchored proteins lead to rare syndromes called glycosylphosphatidylinositol-anchored proteins biosynthesis defects. This study aimed to provide a systematic review of GPIBD cases reports published at any time in English-language literature.
Methods
The inclusion criteria were: studies on humans, age at onset (< 18 y.o.), report of GPIBD cases with adequate data on the genetic background and symptomatology; whereas exclusion criteria were: publication type (manuscripts, personal communication, review articles); reports of cases of GPI biosynthesis genes mutations in terms of other disorders other than GPIBD, reports of GPIBD cases concentrating on non-neurological symptoms, articles concentrating solely on the genetic issues of GPI biosynthesis. Risk of bias was assessed using Joanna Brigs Institute Critical Appraisal Checklists. Data synthesis was conducted using STATISTICA 13.3.721.1 (StatSoft Polska Sp. z.o.o.). Used tests were: chi-square, Fisher's exact test (for differences in phenotype); Mann-Whitney U test.
Results
Browsing returned the total of 973 articles, which after ruling out the repetitions and assessing the inclusion and exclusion criteria led to final inclusion of 77 articles (337 GPIBD cases) into the analysis. The main outcomes were prevalence of neurological symptoms, onset and semiology of seizures and their response to treatment, onset of developmental delay. Based on this data a synthesis of phenotypical differences between the groups of GPIBD cases and the general GPIBD cases population was made.Synthesis of results presented main features of these disorders, consisting of general development delay, hypotonia and epileptic seizures of varied semiology and time of onset. Most frequently seizures presented with both focal and generalized motor symptoms (myoclonic, tonic). 
Discussion
AFor the first time a synthetical analysis of neurological components in clinical image of glycosylphosphatidylinositol-anchored proteins biosynthesis defectsGPIBD patients was presented. It highlights the main features of these disorders, which might be useful in clinical practice for consideration in differential diagnosis with children presenting with early-onset seizures and developmental delay. The limitation of this review is the scarcity of the specific data in some reports, concerning the semiology and onset of two main features of GPIBD: epileptic seizures and developmental delay.