Turki Abrar, Stockler Sylvia, Sirrs Sandra, Duddy Kathleen, Ho Gloria, Elango Rajavel
BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.
Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
Mol Genet Metab Rep. 2023 Jan 3;34:100955. doi: 10.1016/j.ymgmr.2023.100955. eCollection 2023 Mar.
Glycogen storage disease type Ib (GSD Ib) is an autosomal recessively inherited deficiency of the glucose-6-phosphate translocase (G6PT). Clinical features include a combination of a metabolic phenotype (fasting hypoglycemia, lactic acidosis, hepatomegaly) and a hematologic phenotype with neutropenia and neutrophil dysfunction. Dietary treatment involves provision of starches such as uncooked cornstarch (UCCS) and to provide prolonged enteral supply of glucose. Granulocyte colony-stimulating factor (G-CSF) is the treatment of choice for neutropenia. Because long-term stimulation of hematopoiesis with G-CSF causes serious complications such as splenomegaly, hypersplenism, and osteopenia; hematopoietic stem cell transplantation (HSCT) has been considered in some patients with GSD Ib to correct neutropenia and avoid G-CSF related adverse effects. Whether HSCT also has an effect on the metabolic phenotype and utilization of carbohydrate sources has not been determined.
Our objective was to measure the utilization of starch in a patient with GSD Ib before and after HSCT using the minimally invasive C-glucose breath test (C-GBT).
A case of GSD Ib (18y; female) underwent C-GBT four times: UCCS (pre-HSCT), UCCS (3, 5 months post-HSCT) and (6 months post-HSCT) with a dose of 80 g administered via nasogastric tube after a 4 h fast according to our patient's fasting tolerance. Breath samples were collected at baseline and every 30 min for 240 min. Rate of CO production was measured at 120 min using indirect calorimetry. Finger-prick blood glucose was measured using a glucometer hourly to test hypoglycemia (glucose <4 mmol/L). Biochemical and clinical data were obtained from the medical records as a post-hoc chart review.
UCCS utilization was significantly higher in GSD Ib pre-HSCT, which reduced and stabilized 5 months post-HSCT. UCCS and utilizations were low and not different at 5 and 6 months post-HSCT. Blood glucose concentrations were not significantly different at any time point.
Findings show that HSCT stabilized UCCS utilization, as reflected by lower and stable glucose oxidation. The results also illustrate the application of C-GBT to examine glucose metabolism in response to various carbohydrate sources after other treatment modalities like HSCT in GSD Ib.
糖原贮积病 Ib 型（GSD Ib）是一种常染色体隐性遗传的葡萄糖 -6- 磷酸转运体（G6PT）缺乏症。临床特征包括代谢表型（空腹低血糖、乳酸性酸中毒、肝肿大）和血液学表型（中性粒细胞减少和中性粒细胞功能障碍）的组合。饮食治疗包括提供淀粉类食物，如未经煮熟的玉米淀粉（UCCS），以提供长时间的肠道葡萄糖供应。粒细胞集落刺激因子（G-CSF）是治疗中性粒细胞减少的首选药物。由于长期使用 G-CSF 刺激造血会导致严重并发症，如脾肿大、脾功能亢进和骨质减少；一些 GSD Ib 患者考虑进行造血干细胞移植（HSCT）以纠正中性粒细胞减少并避免与 G-CSF 相关的不良反应。HSCT 是否也对代谢表型和碳水化合物来源的利用有影响尚未确定。
我们的目的是使用微创 C - 葡萄糖呼气试验（C - GBT）测量一名 GSD Ib 患者在 HSCT 前后淀粉的利用情况。
一名 GSD Ib 患者（18 岁；女性）接受了 4 次 C - GBT：UCCS（HSCT 前）、UCCS（HSCT 后 3、5 个月）和 （HSCT 后 6 个月），根据患者的空腹耐受性，禁食 4 小时后经鼻胃管给予 80 g 剂量。在基线和每 30 分钟收集一次呼气样本，共收集 240 分钟。在 120 分钟时使用间接量热法测量 CO 产生率。每小时使用血糖仪测量指尖血糖以检测低血糖（血糖 <4 mmol/L）。作为事后病历审查，从病历中获取生化和临床数据。
GSD Ib 患者 HSCT 前 UCCS 的利用率显著更高，在 HSCT 后 5 个月降低并稳定。HSCT 后 5 个月和 6 个月时 UCCS 和 的利用率较低且无差异。在任何时间点血糖浓度均无显著差异。
研究结果表明，HSCT 稳定了 UCCS 的利用率，这表现为较低且稳定的葡萄糖氧化。结果还说明了 C - GBT 在检测 GSD Ib 患者接受 HSCT 等其他治疗方式后对各种碳水化合物来源的葡萄糖代谢反应中的应用。
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