El-Beshlawy Amal, Tylki-Szymanska Anna, Vellodi Ashok, Belmatoug Nadia, Grabowski Gregory A, Kolodny Edwin H, Batista Julie L, Cox Gerald F, Mistry Pramod K
Pediatric Hospital of Cairo University, Cairo, Egypt.
Children's Memorial Health Institute, Warsaw, Poland.
Mol Genet Metab. 2017 Jan-Feb;120(1-2):47-56. doi: 10.1016/j.ymgme.2016.12.001. Epub 2016 Dec 6.
In Gaucher disease (GD), deficiency of lysosomal acid β-glucosidase results in a broad phenotypic spectrum that is classified into three types based on the absence (type 1 [GD1]) or presence and severity of primary central nervous system involvement (type 2 [GD2], the fulminant neuronopathic form, and type 3 [GD3], the milder chronic neuronopathic form). Enzyme replacement therapy (ERT) with imiglucerase ameliorates and prevents hematological and visceral manifestations in GD1, but data in GD3 are limited to small, single-center series. The effects of imiglucerase ERT on hematological, visceral and growth outcomes (note: ERT is not expected to directly impact neurologic outcomes) were evaluated during the first 5years of treatment in 253 children and adolescents (<18years of age) with GD3 enrolled in the International Collaborative Gaucher Group (ICGG) Gaucher Registry. The vast majority of GBA mutations in this diverse global population consisted of only 2 mutations: L444P (77%) and D409H (7%). At baseline, GD3 patients exhibited early onset of severe hematological and visceral disease and growth failure. During the first year of imiglucerase treatment, hemoglobin levels and platelet counts increased and liver and spleen volumes decreased, leading to marked decreases in the number of patients with moderate or severe anemia, thrombocytopenia, and hepatosplenomegaly. These improvements were maintained through Year 5. There was also acceleration in linear growth as evidenced by increasing height Z-scores. Despite devastating disease at baseline, the probability of surviving for at least 5years after starting imiglucerase was 92%. In this large, multinational cohort of pediatric GD3 patients, imiglucerase ERT provided a life-saving and life-prolonging benefit for patients with GD3, suggesting that, with proper treatment, many such severely affected patients can lead productive lives and contribute to society.
在戈谢病（GD）中，溶酶体酸性β-葡萄糖苷酶缺乏会导致广泛的表型谱，根据是否存在原发性中枢神经系统受累（1型[GD1]无受累，2型[GD2]为暴发性神经病变型，3型[GD3]为较轻度的慢性神经病变型）分为三种类型。用伊米苷酶进行酶替代疗法（ERT）可改善并预防GD1的血液学和内脏表现，但GD3的数据仅限于小型单中心研究系列。在国际协作戈谢病研究组（ICGG）戈谢病登记处登记的253例年龄小于18岁的GD3儿童和青少年治疗的前5年中，评估了伊米苷酶ERT对血液学、内脏和生长结局的影响（注意：ERT预计不会直接影响神经学结局）。在这个多样化的全球人群中，绝大多数GBA突变仅由两种突变组成：L444P（77%）和D409H（7%）。基线时，GD3患者表现出严重血液学和内脏疾病及生长衰竭的早发。在伊米苷酶治疗的第一年，血红蛋白水平和血小板计数升高，肝脏和脾脏体积减小，导致中度或重度贫血、血小板减少和肝脾肿大患者数量显著减少。这些改善持续到第5年。身高Z评分增加证明线性生长也加速了。尽管基线时病情严重，但开始伊米苷酶治疗后至少存活5年的概率为92%。在这个大型多国籍儿科GD3患者队列中，伊米苷酶ERT为GD3患者提供了挽救生命和延长生命的益处，表明通过适当治疗，许多这类严重受累患者可以过上有意义的生活并为社会做出贡献。
