Defining the Phenotype and Assessing Severity in Phosphoglucomutase-1 Deficiency
Defining the Phenotype and Assessing Severity in Phosphoglucomutase-1 Deficiency
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DOI：
10.1016/j.jpeds.2016.04.021
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发表时间：
2016-08-01
影响因子：
5.1
通讯作者：
Morava, Eva
中科院分区：
文献类型：
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作者：
Wong, Sunnie Yan-Wai;Beamer, Lesa J.;Morava, Eva
目的 定义磷酸葡萄糖变位酶 1 缺乏症 (PGM1-CDG) 患者的表型组并确定疾病严重程度的预测因素。研究设计 我们评估了 27 名 PGM1-CDG 患者，将其分为 3 个表型组，并通过评分系统杜兰 PGM1-CDG 评定量表 (TPCRS) 验证分组分配。该量表评估 PGM1-CDG 的可测量临床特征。我们通过回归分析检查了基因型、酶活性和 TPCRS 评分之间的关系。通过主成分分析评估最常见的临床特征和疾病严重程度之间的关联。结果我们发现表型组中 TPCRS 评分存在统计学上显着的分层 (P < .001)。回归分析显示，基因型、酶活性和TPCRS评分之间不存在显着相关性。主成分分析确定了导致队列中 54% 方差的 5 个变量，可预测疾病严重程度：先天性畸形、心脏受累、内分泌缺陷、肌病和生长。 结论 我们建立了一种评分算法，可根据 PGM1-CDG 患者的临床病史和表现可靠地评估其疾病严重程度。我们还确定了 5 个可预测疾病严重程度的临床特征；其中 2 个特征可以通过体检进行评估，无需进行特定的诊断测试，从而可以快速评估和开始治疗。
Objective To define phenotypic groups and identify predictors of disease severity in patients with phosphoglucomutase-1 deficiency (PGM1-CDG).Study design We evaluated 27 patients with PGM1-CDG who were divided into 3 phenotypic groups, and group assignment was validated by a scoring system, the Tulane PGM1-CDG Rating Scale (TPCRS). This scale evaluates measurable clinical features of PGM1-CDG. We examined the relationship between genotype, enzyme activity, and TPCRS score by using regression analysis. Associations between the most common clinical features and disease severity were evaluated by principal component analysis.Results We found a statistically significant stratification of the TPCRS scores among the phenotypic groups (P < .001). Regression analysis showed that there is no significant correlation between genotype, enzyme activity, and TPCRS score. Principal component analysis identified 5 variables that contributed to 54% variance in the cohort and are predictive of disease severity: congenital malformation, cardiac involvement, endocrine deficiency, myopathy, and growth.Conclusions We established a scoring algorithm to reliably evaluate disease severity in patients with PGM1-CDG on the basis of their clinical history and presentation. We also identified 5 clinical features that are predictors of disease severity; 2 of these features can be evaluated by physical examination, without the need for specific diagnostic testing and thus allow for rapid assessment and initiation of therapy.