6岁男性患儿，因发育迟缓6年，反复发热、抽搐5年就诊。患儿3月龄时发现精神运动发育落后，1岁起出现反复发热、抽搐，伴间断口腔溃疡及扁桃体化脓，发热期间查血白细胞计数、C反应蛋白、红细胞沉降率升高，热退后正常，脑电图提示癫痫，基因检测提示GPAA1基因存在复合杂合突变。最终该患儿诊断为糖基磷脂酰肌醇生物合成缺陷15型（glycosylphosphatidylinositol biosynthesis deficiency 15, GPIBD15）、周期性发热。该患儿抗癫痫效果不佳，糖皮质激素治疗对发热有效。该文报道了中国首例GPAA1基因突变导致GPIBD15患儿，对该病基因、临床特点、诊疗等进行归纳总结，为该病的早期诊断、治疗提供参考依据。
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.
关键词
糖基磷脂酰肌醇生物合成缺陷15型 /
GPAA1基因 /
癫痫 /
周期性发热 /
儿童
Key words
Glycosylphosphatidylinositol biosynthesis deficiency 15 /
GPAA1 gene /
Epilepsy /
Periodic fever /
Child
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参考文献
1 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.
2 Castle AMR, Salian S, Bassan H, et al. Expanding the phenotypic spectrum of GPI anchoring deficiency due to biallelic variants in GPAA1[J]. Neurol Genet, 2021, 7(6): e631. PMID: 34703884. PMCID: PMC8532669. DOI: 10.1212/NXG.0000000000000631.
3 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.
4 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.
5 Rydzynska Z, Pawlik B, Krzyzanowski D, et al. Neutrophil elastase defects in congenital neutropenia[J]. Front Immunol, 2021, 12: 653932. PMID: 33968054. PMCID: PMC8100030. DOI: 10.3389/fimmu.2021.653932.
6 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.
7 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.
8 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.
9 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.
10 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.
11 Xu Y, Jin Y, Gao S, et al. Prognostic signature and therapeutic value based on membrane lipid biosynthesis-related genes in breast cancer[J]. J Oncol, 2022, 2022: 7204415. PMID: 36059802. PMCID: PMC9436593. DOI: 10.1155/2022/7204415.
12 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.
13 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.
14 Sabitha KR, Shetty AK, Upadhya D. Patient-derived iPSC modeling of rare neurodevelopmental disorders: molecular pathophysiology and prospective therapies[J]. Neurosci Biobehav Rev, 2021, 121: 201-219. PMID: 33370574. PMCID: PMC7962756. DOI: 10.1016/j.neubiorev.2020.12.025.
15 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.
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