LAMA2相关肌营养不良症早期自然史国际回顾性研究

IF 3.2 4区 医学 Q2 CLINICAL NEUROLOGY
Lauren Hinkley, Rotem Orbach, Justin Park, Rachel Alvarez, Gustavo Dziewczapolski, Carsten G Bönnemann, A Reghan Foley
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引用次数: 0

摘要

背景:LAMA2相关肌营养不良症(LAMA2-RDs)是先天性肌营养不良症中最常见的一种,历来被分为两种亚型:完全或部分缺乏层粘连蛋白-211(美罗素)。LAMA2-RD患者具有典型的先天表型,表现为重症肌无力、运动发育迟缓、关节挛缩、发育不良和进行性呼吸功能不全:虽然已对 5 岁以上的 LAMA2-RD 患者进行了全面的前瞻性自然史研究,但尚未对 5 岁及以下 LAMA2-RD 患者的早期自然史进行全面描述:我们通过先天性肌肉疾病国际登记处(CMDIR)提取了出生至 5 岁 LAMA2-RD 患者的回顾性数据。我们采用基于最大运动里程碑的表型分类法对数据进行分析,将患者分为两个表型组:"坐 "指的是那些能够保持坐姿的患者,而 "走 "指的是那些在 3.5 岁之前能够独立行走的患者:来自10个国家的60名LAMA2-RD患者符合纳入标准。24名患者在5岁前开始接受无创通气治疗。出生后最初几年的住院治疗通常与呼吸功能不全有关。喂养/营养困难和矫形问题也是常见的报道。新生儿期观察到的肌酸激酶(CK)显著升高在出生后的头几个月内迅速下降:这是迄今为止国际上规模最大的LAMA2-RD早期自然史回顾性研究,为了解LAMA2-RD的早期临床发现提供了重要数据,这些数据与国际前瞻性早期自然史研究中收集的数据一起,将有助于确定临床试验的准备情况。我们提出的LAMA2-RD1和LAMA2-RD2命名法,前者代表患者能够坐下(保持坐姿),后者代表患者能够独立行走,旨在进一步改进LAMA2-RD的分类。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An International Retrospective Early Natural History Study of LAMA2-Related Dystrophies.

Background: LAMA2-related dystrophies (LAMA2-RDs) represent one of the most common forms of congenital muscular dystrophy and have historically been classified into two subtypes: complete or partial deficiency of laminin-211 (merosin). Patients with LAMA2-RD with the typical congenital phenotype manifest severe muscle weakness, delayed motor milestones, joint contractures, failure to thrive, and progressive respiratory insufficiency.

Objective: While a comprehensive prospective natural history study has been performed in LAMA2-RD patients over 5 years of age, the early natural history of patients with LAMA2-RD 5 years and younger has not been comprehensively characterized.

Methods: We extracted retrospective data for patients with LAMA2-RD ages birth through 5 years via the Congenital Muscle Disease International Registry (CMDIR). We analyzed the data using a phenotypic classification based on maximal motor milestones to divide patients into two phenotypic groups: "Sit" for those patients who attained that ability to remain seated and "Walk" for those patients who attained the ability to walk independently by 3.5 years of age.

Results: Sixty patients with LAMA2-RD from 10 countries fulfilled the inclusion criteria. Twenty-four patients had initiated non-invasive ventilation by age 5 years. Hospitalizations during the first years of life were often related to respiratory insufficiency. Feeding/nutritional difficulties and orthopedic issues were commonly reported. Significant elevations of creatine kinase (CK) observed during the neonatal period declined rapidly within the first few months of life.

Conclusions: This is the largest international retrospective early natural history study of LAMA2-RD to date, contributing essential data for understanding early clinical findings in LAMA2-RD which, along with the data being collected in international, prospective early natural history studies, will help to establish clinical trial readiness. Our proposed nomenclature of LAMA2-RD1 for patients who attain the ability to sit (remain seated) and LAMA2-RD2 for patients who attain the ability to walk independently is aimed at further improving LAMA2-RD classification.

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来源期刊
Journal of neuromuscular diseases
Journal of neuromuscular diseases Medicine-Neurology (clinical)
CiteScore
5.10
自引率
6.10%
发文量
102
期刊介绍: The Journal of Neuromuscular Diseases aims to facilitate progress in understanding the molecular genetics/correlates, pathogenesis, pharmacology, diagnosis and treatment of acquired and genetic neuromuscular diseases (including muscular dystrophy, myasthenia gravis, spinal muscular atrophy, neuropathies, myopathies, myotonias and myositis). The journal publishes research reports, reviews, short communications, letters-to-the-editor, and will consider research that has negative findings. The journal is dedicated to providing an open forum for original research in basic science, translational and clinical research that will improve our fundamental understanding and lead to effective treatments of neuromuscular diseases.
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