Carvalho Patrícia Margarida Serra, Silva Nuno José Marques Mendes, Dias Patrícia Glória Dinis, Porto João Filipe Cordeiro, Santos Lèlita Conceição, Costa José Manuel Nascimento
Internal Medicine Ward, Coimbra University Hospital, Av, Bissaya Barreto e Praceta Prof, Mota Pinto, 3000-075, Coimbra, Portugal.
J Diabetes Metab Disord. 2013 Jun 6;12(1):25. doi: 10.1186/2251-6581-12-25.
Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disorder, caused by deficient activity of glucose-6-phosphatase-α. It produces fasting induced hypoglycemia and hepatomegaly, usually manifested in the first semester of life. Besides, it is also associated with growth delay, anemia, platelet dysfunction, osteopenia and sometimes osteoporosis. Hyperlipidemia and hyperuricemia are almost always present and hepatocellular adenomas and renal dysfunction frequent late complications.
The authors present a report of five adult patients with GSD Ia followed in internal medicine appointments and subspecialties.
Four out of five patients were diagnosed in the first 6 months of life, while the other one was diagnosed in adult life after the discovery of hepatocellular adenomas. In two cases genetic tests were performed, being identified the missense mutation R83C in one, and the mutation IVS4-3C > G in the intron 4 of glucose-6-phosphatase gene, not previously described, in the other. Growth retardation was present in 3 patients, and all of them had anemia, increased bleeding tendency and hepatocellular adenomas; osteopenia/osteoporosis was present in three cases. All but one patient had marked hyperlipidemia and hyperuricemia, with evidence of endothelial dysfunction in one case and of brain damage with refractory epilepsy in another case. Proteinuria was present in two cases and end-stage renal disease in another case. There was a great variability in the dietary measures; in one case, liver transplantation was performed, with correction of the metabolic derangements.
Hyperlipidemia is almost always present and only partially responds to dietary and drug therapy; liver transplantation is the only definitive solution. Although its association with premature atherosclerosis is rare, there have been reports of endothelial dysfunction, raising the possibility for increased cardiovascular risk in this group of patients. Being a rare disease, no single metabolic center has experience with large numbers of patients and the recommendations are based on clinical experience more than large scale studies.
Ia型糖原贮积病（GSD Ia）是一种罕见的代谢紊乱疾病，由葡萄糖-6-磷酸酶-α活性缺乏引起。它会导致空腹诱发的低血糖和肝肿大，通常在生命的第一学期出现。此外，它还与生长发育迟缓、贫血、血小板功能障碍、骨质减少甚至有时与骨质疏松有关。高脂血症和高尿酸血症几乎总是存在，肝细胞腺瘤和肾功能障碍是常见的晚期并发症。
作者报告了五例成年GSD Ia患者在内科门诊和专科随访的情况。
五例患者中有四例在出生后的前6个月被诊断出，而另一例在成年后发现肝细胞腺瘤时才被诊断。两例患者进行了基因检测，其中一例鉴定出错义突变R83C，另一例在葡萄糖-6-磷酸酶基因的内含子4中鉴定出此前未描述的突变IVS4-3C＞G。3例患者存在生长发育迟缓，所有患者均有贫血、出血倾向增加和肝细胞腺瘤；3例患者存在骨质减少/骨质疏松。除1例患者外，所有患者均有明显的高脂血症和高尿酸血症，1例有内皮功能障碍证据，另1例有难治性癫痫导致的脑损伤。2例患者出现蛋白尿，另1例患者出现终末期肾病。饮食措施差异很大；1例患者进行了肝移植，代谢紊乱得到纠正。
高脂血症几乎总是存在，对饮食和药物治疗仅部分有效；肝移植是唯一的确定性解决方案。虽然其与早发性动脉粥样硬化的关联罕见，但已有内皮功能障碍的报道，增加了该组患者心血管风险升高的可能性。由于这是一种罕见疾病，没有单一的代谢中心有大量患者的治疗经验，相关建议更多基于临床经验而非大规模研究。
