磷酸甘露糖变位酶2缺乏症的诊治进展

周述艳

doi:10.7499/j.issn.1008-8830.2209049

PDF(604 KB)

HTML

中国当代儿科杂志 ›› 2023, Vol. 25 ›› Issue (2) : 223-228. DOI: 10.7499/j.issn.1008-8830.2209049

综述

磷酸甘露糖变位酶2缺乏症的诊治进展

周述艳

作者信息 +

Advances in the diagnosis and treatment of phosphomannomutase 2 deficiency

ZHOU Shu-Yan

Author information +

文章历史 +

摘要

磷酸甘露糖变位酶2缺乏症是最常见的N-糖基化障碍，又称磷酸甘露糖变位酶2相关性先天性糖基化障碍（phosphomannomutase 2-congenital disorder of glycosylation，PMM2-CDG），是一种常染色体隐性遗传的多系统疾病，由PMM2基因（OMIM：601785）突变所致，病情轻重不一，目前尚无针对PMM2-CDG的特异疗法，早发现、早诊断、早治疗可有效延长患儿的生存年限。该文就PMM2-CDG的诊疗进展进行综述。

Abstract

Phosphomannomutase 2 deficiency is the most common form of N-glycosylation disorders and is also known as phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG). It is an autosomal recessive disease with multi-system involvements and is caused by mutations in the PMM2 gene (OMIM: 601785), with varying severities in individuals. At present, there is still no specific therapy for PMM2-CDG, and early identification, early diagnosis, and early treatment can effectively prolong the life span of pediatric patients. This article reviews the advances in the diagnosis and treatment of PMM2-CDG.

导出引用

周述艳. 磷酸甘露糖变位酶2缺乏症的诊治进展[J]. 中国当代儿科杂志. 2023, 25(2): 223-228 https://doi.org/10.7499/j.issn.1008-8830.2209049

ZHOU Shu-Yan. Advances in the diagnosis and treatment of phosphomannomutase 2 deficiency[J]. Chinese Journal of Contemporary Pediatrics. 2023, 25(2): 223-228 https://doi.org/10.7499/j.issn.1008-8830.2209049

参考文献

1 Pajusalu S, Vals MA, Mihkla L, et al. The estimated prevalence of N-linked congenital disorders of glycosylation across various populations based on allele frequencies in general population databases[J]. Front Genet, 2021, 12: 719437. PMID: 34447415. PMCID: PMC8383291. DOI: 10.3389/fgene.2021.719437.
2 Chang IJ, He M, Lam CT. Congenital disorders of glycosylation[J]. Ann Transl Med, 2018, 6(24): 477. PMID: 30740408. PMCID: PMC6331365. DOI: 10.21037/atm.2018.10.45.
3 ?echová A, Honzík T, Edmondson AC, et al. Should patients with phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?[J]. Mol Genet Metab, 2021, 133(4): 397-399. PMID: 34140212. PMCID: PMC8754259. DOI: 10.1016/j.ymgme.2021.06.003.
4 Vaes L, Rymen D, Cassiman D, et al. Genotype-phenotype correlations in PMM2-CDG[J]. Genes (Basel), 2021, 12(11): 1658. PMID: 34828263. PMCID: PMC8620515. DOI: 10.3390/genes12111658.
5 Freeze HH, Eklund EA, Ng BG, et al. Neurological aspects of human glycosylation disorders[J]. Annu Rev Neurosci, 2015, 38: 105-125. PMID: 25840006. PMCID: PMC4809143. DOI: 10.1146/annurev-neuro-071714-034019.
6 查剑, 曹芳芳, 徐瑜欣, 等. 以偏瘫就诊的PMM2相关性先天性糖基化障碍1例报告并文献复习[J]. 实用临床医学, 2021, 22(2): 30-33. DOI: 10.13764/j.cnki.lcsy.2021.02.011.
7 de Diego V, Martínez-Monseny AF, Muchart J, et al. Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG)[J]. J Inherit Metab Dis, 2017, 40(5): 709-713. PMID: 28341975. DOI: 10.1007/s10545-017-0028-4.
8 Feraco P, Mirabelli-Badenier M, Severino M, et al. The shrunken, bright cerebellum: a characteristic MRI finding in congenital disorders of glycosylation type 1a[J]. AJNR Am J Neuroradiol, 2012, 33(11): 2062-2067. PMID: 22723063. PMCID: PMC7965601. DOI: 10.3174/ajnr.A3151.
9 Pettinato F, Mostile G, Battini R, et al. Clinical and radiological correlates of activities of daily living in cerebellar atrophy caused by PMM2 mutations (PMM2-CDG)[J]. Cerebellum, 2021, 20(4): 596-605. PMID: 33619652. PMCID: PMC8360885. DOI: 10.1007/s12311-021-01242-x.
10 Bogdańska A, Lipiński P, Szymańska-Ro?ek P, et al. Clinical, biochemical and molecular phenotype of congenital disorders of glycosylation: long-term follow-up[J]. Orphanet J Rare Dis, 2021, 16(1): 17. PMID: 33407696. PMCID: PMC7789416. DOI: 10.1186/s13023-020-01657-5.
11 Schiff M, Roda C, Monin ML, et al. Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature[J]. J Med Genet, 2017, 54(12): 843-851. PMID: 28954837. DOI: 10.1136/jmedgenet-2017-104903.
12 Witters P, Honzik T, Bauchart E, et al. Long-term follow-up in PMM2-CDG: are we ready to start treatment trials?[J]. Genet Med, 2019, 21(5): 1181-1188. PMID: 30293989. DOI: 10.1038/s41436-018-0301-4.
13 Al-Maawali AA, Miller E, Schulze A, et al. Subcutaneous fat pads on body MRI—an early sign of congenital disorder of glycosylation PMM2-CDG (CDG1a)[J]. Pediatr Radiol, 2014, 44(2): 222-225. PMID: 24037084. DOI: 10.1007/s00247-013-2782-2.
14 Ferreira CR, Altassan R, Marques-Da-Silva D, et al. Recognizable phenotypes in CDG[J]. J Inherit Metab Dis, 2018, 41(3): 541-553. PMID: 29654385. PMCID: PMC5960425. DOI: 10.1007/s10545-018-0156-5.
15 王媛媛, 曾永梅. 先天性糖基化障碍疾病累及肝脏的临床表现[J]. 国际儿科学杂志, 2021, 48(5): 323-326. DOI: 10.3760/cma.j.issn.1673-4408.2021.05.009.
16 Colantuono R, D'Acunto E, Melis D, et al. Liver involvement in congenital disorders of glycosylation: a systematic review[J]. J Pediatr Gastroenterol Nutr, 2021, 73(4): 444-454. PMID: 34173795. PMCID: PMC9255677. DOI: 10.1097/MPG.0000000000003209.
17 Starosta RT, Boyer S, Tahata S, et al. Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up[J]. Orphanet J Rare Dis, 2021, 16(1): 20. PMID: 33413482. PMCID: PMC7788939. DOI: 10.1186/s13023-020-01630-2.
18 Altassan R, Péanne R, Jaeken J, et al. International clinical guidelines for the management of phosphomannomutase 2-congenital disorders of glycosylation: diagnosis, treatment and follow up[J]. J Inherit Metab Dis, 2019, 42(1): 5-28. PMID: 30740725. DOI: 10.1002/jimd.12024.
19 Macchia PE, Harrison HH, Scherberg NH, et al. Thyroid function tests and characterization of thyroxine-binding globulin in the carbohydrate-deficient glycoprotein syndrome type I[J]. J Clin Endocrinol Metab, 1995, 80(12): 3744-3749. PMID: 8530628. DOI: 10.1210/jcem.80.12.8530628.
20 Vurall? D, Y?ld?z Y, Ozon A, et al. Hyperinsulinism may be underreported in hypoglycemic patients with phosphomannomutase 2 deficiency[J]. J Clin Res Pediatr Endocrinol, 2022, 14(3): 275-286. PMID: 35308014. PMCID: PMC9422911. DOI: 10.4274/jcrpe.galenos.2022.2021-10-14.
21 陈璇, 陈金龙, 程学英, 等. 先天性糖基化障碍Ia型并扩张型心肌病1例[J]. 中华实用儿科临床杂志, 2021, 36(18): 1426-1428. DOI: 10.3760/cma.j.cn101070-20200410-00615.
22 Kasapkara ?S, Bar?? Z, K?l?? M, et al. PMM2-CDG and sensorineural hearing loss[J]. J Inherit Metab Dis, 2017, 40(5): 629-630. PMID: 28762107. DOI: 10.1007/s10545-017-0073-z.
23 Lipiński P, St?pień KM, Ciara E, et al. Skeletal and bone mineral density features, genetic profile in congenital disorders of glycosylation: review[J]. Diagnostics (Basel), 2021, 11(8): 1438. PMID: 34441372. PMCID: PMC8391432. DOI: 10.3390/diagnostics11081438.
24 Freeze HH, Eklund EA, Ng BG, et al. Neurology of inherited glycosylation disorders[J]. Lancet Neurol, 2012, 11(5): 453-466. PMID: 22516080. PMCID: PMC3625645. DOI: 10.1016/S1474-4422(12)70040-6.
25 Francisco R, Marques-da-Silva D, Brasil S, et al. The challenge of CDG diagnosis[J]. Mol Genet Metab, 2019, 126(1): 1-5. PMID: 30454869. DOI: 10.1016/j.ymgme.2018.11.003.
26 Lipiński P, Tylki-Szymańska A. Congenital disorders of glycosylation: what clinicians need to know?[J]. Front Pediatr, 2021, 9: 715151. PMID: 34540767. PMCID: PMC8446601. DOI: 10.3389/fped.2021.715151.
27 Stenson PD, Mort M, Ball EV, et al. The Human Gene Mutation Database (HGMD?): optimizing its use in a clinical diagnostic or research setting[J]. Hum Genet, 2020, 139(10): 1197-1207. PMID: 32596782. PMCID: PMC7497289. DOI: 10.1007/s00439-020-02199-3.
28 Yuste-Checa P, Gámez A, Brasil S, et al. The effects of PMM2-CDG-causing mutations on the folding, activity, and stability of the PMM2 protein[J]. Hum Mutat, 2015, 36(9): 851-860. PMID: 26014514. DOI: 10.1002/humu.22817.
29 Lam C, Krasnewich DM. PMM2-CDG[M]. Adam MP, Everman DB, Mirzaa GM, et al. GeneReviews?[Internet]. Seattle (WA): University of Washington, Seattle, 1993.
30 Taday R, Park JH, Grüneberg M, et al. Mannose supplementation in PMM2-CDG[J]. Orphanet J Rare Dis, 2021, 16(1): 359. PMID: 34380532. PMCID: PMC8359111. DOI: 10.1186/s13023-021-01988-x.
31 Schneider A, Thiel C, Rindermann J, et al. Successful prenatal mannose treatment for congenital disorder of glycosylation-Ia in mice[J]. Nat Med, 2011, 18(1): 71-73. PMID: 22157680. DOI: 10.1038/nm.2548.
32 Sharma V, Freeze HH. Mannose efflux from the cells: a potential source of mannose in blood[J]. J Biol Chem, 2011, 286(12): 10193-10200. PMID: 21273394. PMCID: PMC3060472. DOI: 10.1074/jbc.M110.194241.
33 Grünert SC, Marquardt T, Lausch E, et al. Unsuccessful intravenous D-mannose treatment in PMM2-CDG[J]. Orphanet J Rare Dis, 2019, 14(1): 231. PMID: 31640729. PMCID: PMC6805611. DOI: 10.1186/s13023-019-1213-3.
34 Brasil S, Pascoal C, Francisco R, et al. CDG therapies: from bench to bedside[J]. Int J Mol Sci, 2018, 19(5): 1304. PMID: 29702557. PMCID: PMC5983582. DOI: 10.3390/ijms19051304.
35 Iyer S, Sam FS, DiPrimio N, et al. Repurposing the aldose reductase inhibitor and diabetic neuropathy drug epalrestat for the congenital disorder of glycosylation PMM2-CDG[J]. Dis Model Mech, 2019, 12(11): dmm040584. PMID: 31636082. PMCID: PMC6899038. DOI: 10.1242/dmm.040584.
36 Park JH, Marquardt T. Treatment options in congenital disorders of glycosylation[J]. Front Genet, 2021, 12: 735348. PMID: 34567084. PMCID: PMC8461064. DOI: 10.3389/fgene.2021.735348.
37 Ligezka AN, Radenkovic S, Saraswat M, et al. Sorbitol is a severity biomarker for PMM2-CDG with therapeutic implications[J]. Ann Neurol, 2021, 90(6): 887-900. PMID: 34652821. PMCID: PMC8820356. DOI: 10.1002/ana.26245.
38 Liguori L, Monticelli M, Allocca M, et al. Pharmacological chaperones: a therapeutic approach for diseases caused by destabilizing missense mutations[J]. Int J Mol Sci, 2020, 21(2): 489. PMID: 31940970. PMCID: PMC7014102. DOI: 10.3390/ijms21020489.
39 Briso-Montiano A, del Ca?o-Ochoa F, Vilas A, et al. Insight on molecular pathogenesis and pharmacochaperoning potential in phosphomannomutase 2 deficiency, provided by novel human phosphomannomutase 2 structures[J]. J Inherit Metab Dis, 2022, 45(2): 318-333. PMID: 34859900. DOI: 10.1002/jimd.12461.
40 Monticelli M, Liguori L, Allocca M, et al. β-glucose-1,6-bisphosphate stabilizes pathological phophomannomutase2 mutants in vitro and represents a lead compound to develop pharmacological chaperones for the most common disorder of glycosylation, PMM2-CDG[J]. Int J Mol Sci, 2019, 20(17): 4164. PMID: 31454904. PMCID: PMC6747070. DOI: 10.3390/ijms20174164.
41 Tran ML, Génisson Y, Ballereau S, et al. Second-generation pharmacological chaperones: beyond inhibitors[J]. Molecules, 2020, 25(14): 3145. PMID: 32660097. PMCID: PMC7397201. DOI: 10.3390/molecules25143145.
42 Vilas A, Yuste-Checa P, Gallego D, et al. Proteostasis regulators as potential rescuers of PMM2 activity[J]. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(7): 165777. PMID: 32222543. DOI: 10.1016/j.bbadis.2020.165777.
43 Martínez-Monseny AF, Bolasell M, Callejón-Póo L, et al. AZATAX: acetazolamide safety and efficacy in cerebellar syndrome in PMM2 congenital disorder of glycosylation (PMM2-CDG)[J]. Ann Neurol, 2019, 85(5): 740-751. PMID: 30873657. DOI: 10.1002/ana.25457.
44 Serrano M. Stroke-like episodes in PMM2-CDG: when the lack of other evidence is the only evidence[J]. Front Pediatr, 2021, 9: 717864. PMID: 34708008. PMCID: PMC8542667. DOI: 10.3389/fped.2021.717864.
45 Boyer SW, Johnsen C, Morava E. Nutrition interventions in congenital disorders of glycosylation[J]. Trends Mol Med, 2022, 28(6): 463-481. PMID: 35562242. PMCID: PMC9375550. DOI: 10.1016/j.molmed.2022.04.003.
46 Gámez A, Serrano M, Gallego D, et al. New and potential strategies for the treatment of PMM2-CDG[J]. Biochim Biophys Acta, 2020, 1864(11): 129686. PMID: 32712172. DOI: 10.1016/j.bbagen.2020.129686.