Division of GIM, Department of Medicine, University of Washington.
Department of Medicine, University of Washington, Severe Chronic Neutropenia International Registry, Seattle, Washington.
Curr Opin Hematol. 2019 Jan;26(1):16-21. doi: 10.1097/MOH.0000000000000474.
Glycogen storage disease Ib (GSD Ib) is characterized by hepatomegaly, hypoglycemia, neutropenia, enterocolitis and recurrent bacterial infections. It is attributable to mutations in G6PT1, the gene for the glucose-6-phosphate transporter responsible for transport of glucose into the endoplasmic reticulum. Neutropenia in GSD Ib is now frequently treated with granulocyte colony-stimulating factor (G-CSF). We formed a cooperative group to review outcomes of the long-term treatment of GSD Ib patients treated with G-CSF.
The study enrolled 103 patients (48 men and 55 women), including 47 currently adult patients. All of these patients were treated with G-CSF, starting at a median age of 3.8 years (range 0.04-33.9 years) with a median dose of 3.0 mcg/kg/day (range 0.01-93.1 mcg/kg/day) for a median of 10.3 years (range 0.01-29.3 years). Neutrophils increased in response to G-CSF in all patients (median values before G-CSF 0.2 × 10/l, on G-CSF 1.20 x 10/l). Treatment increased spleen size (before G-CSF, 47%, on treatment on G-CSF 76%), and splenomegaly was the dose-limiting adverse effect of treatment (pain and early satiety). Clinical observations and records attest to reduce frequency of infectious events and the severity of inflammatory bowel symptoms, but fever and recurrent infections remain a significant problem. In the cohort of patients followed carefully through the Severe Chronic Neutropenia International Registry, four patients have developed myelodysplasia or acute myeloid leukemia and we are aware of four other cases, (altogether seven on G-CSF, one never treated with G-CSF). Liver transplantation in five patients did not correct neutropenia. Four patients had hematopoietic stem cell transplantation; two adults and two children were transplanted; one adult and one child survived.
GSD Ib is a complex disorder of glucose metabolism causing severe chronic neutropenia. G-CSF is effective to raise blood neutrophil counts and reduce fevers and infections in most patients. In conjunction with other therapies (salicylates, mesalamine sulfasalazine and prednisone), G-CSF ameliorates inflammatory bowel symptoms, but doses must be limited because it increases spleen size associated with abdominal pain.
糖原贮积病 Ib（GSD Ib）的特征为肝肿大、低血糖、中性粒细胞减少、肠炎和反复细菌感染。其归因于葡萄糖-6-磷酸转运蛋白 1（G6PT1）基因突变，该基因负责葡萄糖向内质网的转运。GSD Ib 中的中性粒细胞减少症现在常通过粒细胞集落刺激因子（G-CSF）治疗。我们成立了一个合作小组，来回顾用 G-CSF 治疗的 GSD Ib 患者的长期治疗结果。
该研究纳入了 103 名患者（48 名男性和 55 名女性），其中 47 名患者目前为成人。所有这些患者都接受了 G-CSF 治疗，中位起始年龄为 3.8 岁（范围 0.04-33.9 岁），中位剂量为 3.0 mcg/kg/天（范围 0.01-93.1 mcg/kg/天），中位治疗时间为 10.3 年（范围 0.01-29.3 年）。所有患者的中性粒细胞对 G-CSF 均有反应（G-CSF 治疗前的中位值为 0.2×10/l，G-CSF 治疗后的中位值为 1.20×10/l）。治疗增加了脾脏大小（G-CSF 治疗前为 47%，G-CSF 治疗后为 76%），且脾肿大是治疗的剂量限制不良事件（疼痛和早饱）。临床观察和记录表明，感染事件的频率和炎症性肠病症状的严重程度降低，但发热和反复感染仍是一个重大问题。在严重慢性中性粒细胞减少症国际登记处仔细随访的患者队列中，有 4 名患者发展为骨髓增生异常或急性髓系白血病，我们还了解到另外 4 例（总共 7 例接受 G-CSF 治疗，1 例从未接受 G-CSF 治疗）。5 名患者的肝移植未能纠正中性粒细胞减少症。4 名患者接受了造血干细胞移植；2 名成人和 2 名儿童接受了移植；1 名成人和 1 名儿童存活。
GSD Ib 是一种葡萄糖代谢的复杂疾病，可导致严重的慢性中性粒细胞减少症。G-CSF 可有效提高血液中性粒细胞计数，并降低大多数患者的发热和感染率。与其他治疗方法（水杨酸盐、美沙拉嗪和泼尼松）联合使用时，G-CSF 可改善炎症性肠病症状，但必须限制剂量，因为它会增加与腹痛相关的脾脏大小。
