Glycosylphosphatidylinositol biosynthesis deficiency 15 caused by GPAA1 gene mutation: a rare disease study
CHEN Qiu-Rong, ZHANG Zhen-Jie, LU Yi-Xiu, YUAN Sun-Bi-Xin, LI Ji
Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China (Li J, Email: 42115165@qq.com)
Abstract:A boy, aged 6 years, attended the hospital due to global developmental delay for 6 years and recurrent fever and convulsions for 5 years. The boy was found to have delayed mental and motor development at the age of 3 months and experienced recurrent fever and convulsions since the age of 1 year, with intermittent canker sores and purulent tonsillitis. During the fever period, blood tests showed elevated white blood cell count, C-reactive protein, and erythrocyte sedimentation rate, which returned to normal after the fever subsides. Electroencephalography showed epilepsy, and genetic testing showed compound heterozygous mutations in the GPAA1 gene. The boy was finally diagnosed with glycosylphosphatidylinositol biosynthesis deficiency 15 (GPIBD15) and periodic fever. The patient did not respond well to antiepileptic treatment, but showed successful fever control with glucocorticoid therapy. This article reports the first case of GPIBD15 caused by GPAA1 gene mutation in China and summarizes the genetic features, clinical features, diagnosis, and treatment of this disease, which provides a reference for the early diagnosis and treatment of GPIBD15.
Nguyen TTM, Murakami Y, Sheridan E, et al. Mutations in GPAA1, encoding a GPI transamidase complex protein, cause developmental delay, epilepsy, cerebellar atrophy, and osteopenia[J]. Am J Hum Genet, 2017, 101(5): 856-865. PMID: 29100095. PMCID: PMC5673666. DOI: 10.1016/j.ajhg.2017.09.020.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology[J]. Genet Med, 2015, 17(5): 405-424. PMID: 25741868. PMCID: PMC4544753. DOI: 10.1038/gim.2015.30.
Amarilyo G, Rothman D, Manthiram K, et al. Consensus treatment plans for periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA): a framework to evaluate treatment responses from the childhood arthritis and rheumatology research alliance (CARRA) PFAPA work group[J]. Pediatr Rheumatol Online J, 2020, 18(1): 31. PMID: 32293478. PMCID: PMC7157990. DOI: 10.1186/s12969-020-00424-x.
Ben-Chetrit E, Gattorno M, Gul A, et al. Consensus proposal for taxonomy and definition of the autoinflammatory diseases (AIDs): a Delphi study[J]. Ann Rheum Dis, 2018, 77(11): 1558-1565. PMID: 30100561. DOI: 10.1136/annrheumdis-2017-212515.
Bayat A, Knaus A, Pendziwiat M, et al. Lessons learned from 40 novel PIGA patients and a review of the literature[J]. Epilepsia, 2020, 61(6): 1142-1155. PMID: 32452540. DOI: 10.1111/epi.16545.
Eisenhaber B, Eisenhaber S, Kwang TY, et al. Transamidase subunit GAA1/GPAA1 is a M28 family metallo-peptide-synthetase that catalyzes the peptide bond formation between the substrate protein's omega-site and the GPI lipid anchor's phosphoethanolamine[J]. Cell Cycle, 2014, 13(12): 1912-1917. PMID: 24743167. PMCID: PMC4111754. DOI: 10.4161/cc.28761.
Zhang XX, Ni B, Li Q, et al. GPAA1 promotes gastric cancer progression via upregulation of GPI-anchored protein and enhancement of ERBB signalling pathway[J]. J Exp Clin Cancer Res, 2019, 38(1): 214. PMID: 31118109. PMCID: PMC6532258. DOI: 10.1186/s13046-019-1218-8.
Zhang JX, Wang JH, Sun XG, et al. GPAA1 promotes progression of childhood acute lymphoblastic leukemia through regulating c-myc[J]. Eur Rev Med Pharmacol Sci, 2020, 24(9): 4931-4939. PMID: 32432756. DOI: 10.26355/eurrev_202005_21182.
Murakami Y, Kanzawa N, Saito K, et al. Mechanism for release of alkaline phosphatase caused by glycosylphosphatidylinositol deficiency in patients with hyperphosphatasia mental retardation syndrome[J]. J Biol Chem, 2012, 287(9): 6318-6325. PMID: 22228761. PMCID: PMC3307314. DOI: 10.1074/jbc.M111.331090.
H?chsmann B, Murakami Y, Osato M, et al. Complement and inflammasome overactivation mediates paroxysmal nocturnal hemoglobinuria with autoinflammation[J]. J Clin Invest, 2019, 129(12): 5123-5136. PMID: 31430258. PMCID: PMC6877298. DOI: 10.1172/JCI123501.
Yuan X, Li Z, Baines AC, et al. A hypomorphic PIGA gene mutation causes severe defects in neuron development and susceptibility to complement-mediated toxicity in a human iPSC model[J]. PLoS One, 2017, 12(4): e0174074. PMID: 28441409. PMCID: PMC5404867. DOI: 10.1371/journal.pone.0174074.