Abstract：
BACKGROUND: Glycogen storage disease type 1a (GSD1a) is an inborn genetic disease caused by glucose-6-phosphatase-α (G6Pase-α) deficiency and is often observed to lead to endogenous glucose production disorders manifesting as hypoglycemia, hyperuricemia, hyperlipidemia, lactic acidemia, hepatomegaly, and nephromegaly. The development of GSD1a with diabetes is relatively rare, and the underlying pathogenesis remains unclear.
METHODS: Here we describe a case of a 25-year-old Chinese female patient with GSD1a, who developed uncontrolled type 2 diabetes mellitus (T2DM) as a young adult. The patient was diagnosed with GSD1a disease at the age of 10 and was subsequently treated with an uncooked cornstarch diet. Recently, the patient was treated in our hospital for vomiting and electrolyte imbalance and was subsequently diagnosed with T2DM. Owing to the impaired secretory function of the patient\'s pancreatic islets, liver dysfunction, hypothyroidism, severe hyperlipidemia, and huge hepatic adenoma, we adopted diet control, insulin therapy, and hepatic adenoma resection to alleviate this situation. The WES discovered compound heterozygous mutations at the exon 5 of G6PC gene at 17th chromosome in the patient, c.648G>T (p.L216 L, NM_000151.4, rs80356484) in her father and c.674T>C (p.L225 P, NM_000151.4, rs1555560128) in her mother. c.648G>T is a well-known splice-site mutation, which causes CTG changing to CTT at protein 216 and creates a new splicing site 91 bp downstream of the authentic splice site, though both codons encode leucine. c.674T>C is a known missense mutation that causes TGC to become CGC at protein 225, thereby changing from coding for leucine to coding for proline.
CONCLUSIONS: We report a rare case of GSD1a with T2DM. On the basis of the pathogenesis of GSD1a, we recommend attentiveness to possible development of fasting hypoglycemia caused by GSD and postprandial hyperglycemia from diabetes. As the disease is better identified and treated, and as patients with GSD live longer, this challenge may appear more frequently. Therefore, it is necessary to have a deeper and more comprehensive understanding of the pathophysiology of the disease and explore suitable treatment options.
METHODS: Here we describe a case of a 25-year-old Chinese female patient with GSD1a, who developed uncontrolled type 2 diabetes mellitus (T2DM) as a young adult. The patient was diagnosed with GSD1a disease at the age of 10 and was subsequently treated with an uncooked cornstarch diet. Recently, the patient was treated in our hospital for vomiting and electrolyte imbalance and was subsequently diagnosed with T2DM. Owing to the impaired secretory function of the patient\'s pancreatic islets, liver dysfunction, hypothyroidism, severe hyperlipidemia, and huge hepatic adenoma, we adopted diet control, insulin therapy, and hepatic adenoma resection to alleviate this situation. The WES discovered compound heterozygous mutations at the exon 5 of G6PC gene at 17th chromosome in the patient, c.648G>T (p.L216 L, NM_000151.4, rs80356484) in her father and c.674T>C (p.L225 P, NM_000151.4, rs1555560128) in her mother. c.648G>T is a well-known splice-site mutation, which causes CTG changing to CTT at protein 216 and creates a new splicing site 91 bp downstream of the authentic splice site, though both codons encode leucine. c.674T>C is a known missense mutation that causes TGC to become CGC at protein 225, thereby changing from coding for leucine to coding for proline.
CONCLUSIONS: We report a rare case of GSD1a with T2DM. On the basis of the pathogenesis of GSD1a, we recommend attentiveness to possible development of fasting hypoglycemia caused by GSD and postprandial hyperglycemia from diabetes. As the disease is better identified and treated, and as patients with GSD live longer, this challenge may appear more frequently. Therefore, it is necessary to have a deeper and more comprehensive understanding of the pathophysiology of the disease and explore suitable treatment options.
摘要：
背景：糖原贮积病1a型（GSD1a）是一种由葡萄糖-6-磷酸酶-α（G6Pase-α）缺乏引起的先天性遗传疾病，通常观察到导致内源性葡萄糖产生障碍，表现为低血糖，高尿酸血症,高脂血症,乳酸血症,肝肿大,和肾肥大症。GSD1a与糖尿病的发展相对罕见，和潜在的发病机制仍不清楚。
方法：这里我们描述了一例25岁的中国女性GSD1a患者，他们在年轻时发展为不受控制的2型糖尿病（T2DM）。该患者在10岁时被诊断出患有GSD1a疾病，随后接受了未煮熟的玉米淀粉饮食治疗。最近,患者因呕吐和电解质紊乱在我院接受治疗,随后被诊断为2型糖尿病.由于患者胰岛的分泌功能受损，肝功能障碍,甲状腺功能减退,严重的高脂血症，巨大的肝腺瘤,我们采用了饮食控制，胰岛素治疗,和肝腺瘤切除术来缓解这种情况。WES在患者的第17染色体上发现了G6PC基因外显子5的复合杂合突变，c.648G>T（p。L216L,NM_000151.4，rs80356484）在她的父亲和c.674T>C（p。L225P,NM_000151.4，rs1555560128）在她的母亲中。c.648G>T是一种众所周知的剪接位点突变，这导致CTG在蛋白216处变为CTT，并在真正的剪接位点下游91bp产生一个新的剪接位点，虽然两个密码子都编码亮氨酸.c.674T>C是一种已知的错义突变，导致TGC在蛋白质225处变成CGC，从而从编码亮氨酸变为编码脯氨酸。
结论：我们报告了一例罕见的GSD1a合并T2DM病例。在GSD1a发病机制的基础上,我们建议关注GSD引起的空腹低血糖和糖尿病引起的餐后高血糖的可能发展。随着疾病得到更好的识别和治疗，随着GSD患者的寿命延长，这种挑战可能会更频繁地出现。因此,有必要对疾病的病理生理有更深入、更全面的认识,探索合适的治疗方案。
方法：这里我们描述了一例25岁的中国女性GSD1a患者，他们在年轻时发展为不受控制的2型糖尿病（T2DM）。该患者在10岁时被诊断出患有GSD1a疾病，随后接受了未煮熟的玉米淀粉饮食治疗。最近,患者因呕吐和电解质紊乱在我院接受治疗,随后被诊断为2型糖尿病.由于患者胰岛的分泌功能受损，肝功能障碍,甲状腺功能减退,严重的高脂血症，巨大的肝腺瘤,我们采用了饮食控制，胰岛素治疗,和肝腺瘤切除术来缓解这种情况。WES在患者的第17染色体上发现了G6PC基因外显子5的复合杂合突变，c.648G>T（p。L216L,NM_000151.4，rs80356484）在她的父亲和c.674T>C（p。L225P,NM_000151.4，rs1555560128）在她的母亲中。c.648G>T是一种众所周知的剪接位点突变，这导致CTG在蛋白216处变为CTT，并在真正的剪接位点下游91bp产生一个新的剪接位点，虽然两个密码子都编码亮氨酸.c.674T>C是一种已知的错义突变，导致TGC在蛋白质225处变成CGC，从而从编码亮氨酸变为编码脯氨酸。
结论：我们报告了一例罕见的GSD1a合并T2DM病例。在GSD1a发病机制的基础上,我们建议关注GSD引起的空腹低血糖和糖尿病引起的餐后高血糖的可能发展。随着疾病得到更好的识别和治疗，随着GSD患者的寿命延长，这种挑战可能会更频繁地出现。因此,有必要对疾病的病理生理有更深入、更全面的认识,探索合适的治疗方案。
