在巴西，使用普通X线摄影优化1型戈谢病患儿的骨骼预后。

Mota Ronald M V, Mankin Henry

Department of Pediatric Orthopedics, Socor Hospital, Belo Horizonte, Brazil.

J Pediatr Orthop. 2007 Apr-May;27(3):347-50. doi: 10.1097/BPO.0b013e3180340d9f.

BACKGROUND

Gaucher disease is the most common lysosomal storage disease and is caused by deficient production and activity of the lysosomal enzyme beta-glucosidase (glucocerebrosidase), resulting in progressive accumulation of glucosylceramide (glucocerebroside) in lysosomes of cells of the reticuloendothelial system in the spleen, liver, and marrow. Clinical manifestations include anemia, thrombocytopenia, hepatosplenomegaly, and bone complications, including bone pain, bone marrow infiltration, lytic lesions, osteopenia, pathological fractures, and avascular necrosis. Early, adequate, and sustained treatment with enzyme replacement therapy (ERT) available since 1991 can change the natural history of the disease, particularly in children. Skeletal complications are usually the major source of disease morbidity and disability and although magnetic resonance imaging and dual-energy x-ray absorptiometry densitometry are recommended for monitoring, these are not readily available in all countries.

METHODS

We describe 18 Brazilian children with type 1 Gaucher disease with bone involvement who were followed with plain radiography for at least 8 months after beginning imiglucerase ERT (initial dose, 15-60 U/kg body weight/15 days). Bone involvement noted by plain radiograph included marrow infiltration, osteopenia, pathological fractures, osteonecrosis, lytic lesions, and Erlenmeyer flask deformity. Patients were questioned about bone crises.

RESULTS

Patients were followed for up to 10 years (mean follow-up, 4 years and 4 months +/- 3 years and 3 months). Bone changes were visible by plain radiographs in all patients. Clinical and radiological improvement was noted in 13 (72%) of 18 patients; bone lesions worsened in 5 (28%) of 18 patients. The final ERT dose for the 13 patients who improved was 55 +/- 10 U/kg (range, 30-60 U/kg), and the final ERT dose for the 5 who worsened was 29 +/- 2 U/kg (range, 26-30 U/kg); this difference was statistically significant (P < 0.03).

CONCLUSIONS

When other imaging technologies are not available, skeletal response to ERT in children with type 1 Gaucher disease can be monitored effectively by plain radiography. Higher doses of ERT (50-60 U/kg /15 days) may be required for improvement of skeletal manifestations.

CLINICAL EVIDENCE

Case series; level 4.

背景

戈谢病是最常见的溶酶体贮积病，由溶酶体酶β-葡萄糖苷酶（葡糖脑苷脂酶）产生不足和活性缺乏所致，导致脾、肝和骨髓中网状内皮系统细胞的溶酶体内葡糖神经酰胺（葡糖脑苷脂）进行性蓄积。临床表现包括贫血、血小板减少、肝脾肿大以及骨骼并发症，如骨痛、骨髓浸润、溶骨性病变、骨质减少、病理性骨折和缺血性坏死。自1991年以来可用的酶替代疗法（ERT）进行早期、充分和持续的治疗可改变疾病的自然病程，尤其是在儿童中。骨骼并发症通常是疾病发病和致残的主要原因，尽管推荐使用磁共振成像和双能X线吸收法骨密度测定进行监测，但并非所有国家都能轻易获得这些检查。

方法

我们描述了18例1型戈谢病合并骨骼受累的巴西儿童，在开始使用伊米苷酶ERT（初始剂量，15 - 60 U/kg体重/15天）后，采用X线平片随访至少8个月。X线平片显示的骨骼受累包括骨髓浸润、骨质减少、病理性骨折、骨坏死、溶骨性病变和烧瓶样畸形。询问患者有关骨危象的情况。

结果

患者随访长达10年（平均随访4年4个月±3年3个月）。所有患者的骨骼变化在X线平片上均可见。18例患者中有13例（72%）临床和影像学表现改善；18例患者中有5例（28%）骨病变恶化。13例病情改善患者的最终ERT剂量为55±10 U/kg（范围30 - 60 U/kg），5例病情恶化患者的最终ERT剂量为29±2 U/kg（范围26 - 30 U/kg）；这种差异具有统计学意义（P < 0.03）。