糖原贮积症Ia型患者的健康教育及管理方法

糖原贮积症（GSD）是一组主要累及肝脏和横纹肌,以肝脏肿大、低血糖为突出表现的遗传代谢病,发病率在（1／2～2．5）万。根据病变位点的不同,可分为12型。GSDIa型是GSD中最常见的一型,又称肝肾型GSD,为常染色体隐性遗传,发病率为l／（10～30）万。系由肝、肾组织中的微粒体酶葡萄糖-6-磷酸酶（G6Pase）活性缺乏所致。     

肝糖原贮积症2例

糖原贮积症(GSD)是一种罕见的隐性遗传性疾病,由于糖原合成分解过程中某些酶的遗传性缺陷或结构异常,导致机体各组织细胞内糖原异常增多的一组疾病,肝糖原贮积症是糖原贮积症较常见的类型[1].     

肝糖原贮积症超声表现1例

患者男,22岁,以"头晕、脚踝疼痛2周"入院.体检:面色苍白,肝脏肿大,脚踝轻度压痛.实验室检查:血红蛋白降低,碱性磷酸酶、γ-谷氨酰胺、总胆汁酸、尿酸增高,空腹血糖降低,AFP(-).     

5例晚发型糖原贮积症Ⅱ型患者的临床分析

目的:探讨糖原贮积症的临床病理特征。方法:对5例晚发型糖原贮积症患者的临床、病理资料进行回顾性分析,并进行病理形态学、特殊染色及电镜观察。结果:本组5例患者体格检查显示四肢远近端、躯体肌肉均匀萎缩;四肢肌张力不同程度降低,颈肌力量稍差,Gewer征阳性。实验室检查血清肌酸激酶(CK)均有不同程度升高。肌电图显示多呈肌源性损害表现,其中3例伴强直样放电及飞机俯冲声。光镜下肌纤维束膜基本完整,染色不均,肌原纤维结构破坏,肌浆内空泡形成,部分肌纤维内见大量颗粒状物质堆积,HE染色表现为颗粒蓝染,GMR红染,PAS深染,NADH-TR染色显示脱失。电镜观察部分肌原纤维间见糖原颗粒聚集,聚集的糖原颗粒部分游离分散,但大多形成膜包绕的空腔结构。结论:糖原贮积症Ⅱ型是一种罕见的进展性溶酶体贮积病,由位于第17号染色体上的酸性α-葡糖苷酶(GAA)基因突变所致,呈常染色体隐性遗传。晚发型GSDⅡ型患者临床多隐匿起病,对于疑似患者,可根据病理形态学主要受累肌肉内糖原沉积并结合电镜观察及临床表现而得出,确诊及分型则需依靠GAA酶的测定或缺陷酶热点基因突变分析。人重组α-葡糖苷酶治疗该病,使患者预后显著改善...     

肝移植治疗糖原贮积症1例

1病例报告 患者,女,8岁6个月.因腹部膨隆伴发育迟缓七年余,反复恶心、头晕、出汗两年余于2000年8月8日入院.患者七年余前无诱因出现腹部膨隆、发育迟缓,在外院就诊,发现肝肿大、血糖偏低(具体不详),确诊为糖原贮积症Ⅰa型(肝源性低血糖型),一直予饮食疗法,疗效尚可.两年余前开始出现频繁恶心、头晕、出汗等症状,予饮食疗法治疗无好转,发育明显迟缓,身高、体重明显低于同龄儿童.     

Ⅰ型糖原贮积症合并双胎妊娠成功分娩1例的护理

总结1例Ⅰ型肝糖原贮积症合并双胎妊娠成功分娩的护理体会。护理的关键是做好营养支持、心理支持与指导、并发症的观察与护理,同时做好血液净化治疗前后的护理。经过治疗与护理,患者平安分娩,于产后13 d出院。     

儿童Ia型糖原累积症合并肝脏多发腺瘤超声造影表现1例

本病例描述了一位糖原累积症Ia型女性患儿肝脏多发腺瘤的超声造影表现。糖原累积症Ia型是一种较为少见的常染色体隐性遗传病,大部分患者在青春期及成人时才发现肝腺瘤,本病案所报道的患儿仅13岁已出现肝脏多发腺瘤,并进行了肝脏超声造影检查。本病案报道较完整地展示了该糖原累积症Ia型患者的临床表现、实验室检查、超声造影征象、病理和基因检测结果,并进一步讨论了该疾病所致的肝脏多发腺瘤的超声造影表现鉴别要点。     

82例糖原累积症Ⅰa型肝脏受累特点

  目的  探讨糖原累积症(glycogen storage disease, GSD)Ⅰa型的肝脏受累特点。  方法  回顾性分析2006年1月至2013年12月在北京协和医院住院治疗的82例基因确诊为GSD Ⅰa型患儿的临床资料及肝脏影像学结果, 并总结其肝脏受累特点。  结果  82例GSDⅠa型患儿中, 男55例, 女27例; 出现症状平均年龄为(1.2±0.9)岁, 其中42例(54.9%)以发现肝脏肿大为首要原因就诊。13.4%(11/82)患儿出现肝脏腺瘤, 腺瘤出现年龄平均(15.7±3.0)岁(12~23岁); 63.6%(7/11)为多发腺瘤, 36.4%(4/11)为单发腺瘤。单发肝脏腺瘤均位于肝脏右叶, 多发腺瘤均表现为左叶及右叶均有分布。1例患儿行肝动脉栓塞治疗, 1例合并腺瘤癌变。  结论  GSD Ⅰa型是小儿较常见的导致肝脏肿大的遗传代谢病之一, 至青春期左右易发生肝脏腺瘤, 部分癌变。定期随诊腹部超声意义重大。对年长儿不明原因的多发肝脏腺瘤要注意鉴别GSD Ⅰa型。     

82例糖原累积症Ⅰa型肝脏受累特点

目的　探讨糖原累积症（glycogen storage disease,GSD）Ⅰa型的肝脏受累特点。方法　回顾性分析2006年1月至2013年12月在北京协和医院住院治疗的82例基因确诊为GSD Ⅰa型患儿的临床资料及肝脏影像学结果,并总结其肝脏受累特点。结果　82例GSDⅠa型患儿中,男55例,女27例;出现症状平均年龄为(1.2±0.9)岁,其中42例（54.9%）以发现肝脏肿大为首要原因就诊。13.4%（11/82）患儿出现肝脏腺瘤,腺瘤出现年龄平均（15.7±3.0）岁（12²3岁）;63.6%（7/11）为多发腺瘤,36.4%（4/11）为单发腺瘤。单发肝脏腺瘤均位于肝脏右叶,多发腺瘤均表现为左叶及右叶均有分布。1例患儿行肝动脉栓塞治疗,1例合并腺瘤癌变。结论　GSD Ⅰa型是小儿较常见的导致肝脏肿大的遗传代谢病之一,至青春期左右易发生肝脏腺瘤,部分癌变。定期随诊腹部超声意义重大。对年长儿不明原因的多发肝脏腺瘤要注意鉴别GSD Ⅰa型。     

糖原累积症IXa型患儿3例护理

总结2020年8月-2022年3月收治于复旦大学附属儿科医院厦门医院感染科3例糖原累积症IXa型患儿的护理经验, 经过5-15天治疗护理后病情平稳出院。住院期间注意预防术后出血,饮食管理是重点,加强心理护理,预防低血糖的发生,出院后定期门诊随访腹部B超、肝功能和血糖。     

Sonographic findings in type I glycogen storage disease.

PURPOSE: The aim of this study was to document the sonographic appearance and dimensions of the liver and spleen in patients affected by type I glycogen storage disease and to correlate those findings with laboratory data to evaluate the potential role of sonography in diagnosing that disease. METHODS: Fourteen patients (age range, 3-26 years; 10 patients younger than 18 years) with type I glycogen storage disease proved by liver biopsy were studied prospectively with gray-scale sonography, color Doppler sonography, and spectral analysis. The liver, kidneys, spleen, portal system, hepatic veins, and hepatic arteries were evaluated. Laboratory data were correlated with sonographic findings. RESULTS: In 13 (93%), of 14 patients, the liver was enlarged, and in 11 patients (79%), hepatic echogenicity was increased. In 9 patients (64%), both kidneys were enlarged, and in 6 cases (43%), the spleen was enlarged. In all patients, flow in the portal, splenic, and superior mesenteric veins was hepatopetal, and flow in the hepatic veins was triphasic. In 5 patients (36%), both triglyceride and total cholesterol levels were higher than normal. No focal hepatic lesions were identified. Analysis found no significant association between sonographic findings and laboratory data. CONCLUSIONS: The most frequent sonographic findings in patients with type I glycogen storage disease were hepatomegaly, increased hepatic echogenicity, and enlarged kidneys. Sonography may help in the diagnosis of type I glycogen storage disease, but a liver biopsy is required for a definitive diagnosis.     

Enzyme replacement therapy in severe adult-onset glycogen storage disease type II

Glycogen storage disease type II (GSDII) is an autosomal recessive myopathy caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Enzyme replacement therapy (ERT) with recombinant GAA (rh-GAA) has become available for GSDII, although its effectiveness in adults remains unknown. We present a case of ERT with rhGAA in a 49-year-old male with GSDII in a severe stage of the disease. Quantitative magnetic resonance imaging showed an increase in muscle mass of the inferior limb, especially evident on the quadriceps femoris and the patient's body weight increased up to 30%, although his reported dietary habits were the same as before ERT. Beyond improvement in muscle strength and respiratory function, we observed a dramatic increase in body mass index from 12.7 to 16.6 kg/m(2). This may reflect a change from a catabolic state to a more balanced metabolic state during ERT.     

Recombinant AAV-directed gene therapy for type I glycogen storage diseases

Introduction: Glycogen storage disease (GSD) type Ia and Ib are disorders of impaired glucose homeostasis affecting the liver and kidney. GSD-Ib also affects neutrophils. Current dietary therapies cannot prevent long-term complications. In animal studies, recombinant adeno-associated virus (rAAV) vector-mediated gene therapy can correct or minimize multiple aspects of the disorders, offering hope for human gene therapy.

Areas covered: A summary of recent progress in rAAV-mediated gene therapy for GSD-I; strategies to improve rAAV-mediated gene delivery, transduction efficiency and immune avoidance; and vector refinements that improve expression.

Expert opinion: rAAV-mediated gene delivery to the liver can restore glucose homeostasis in preclinical models of GSD-I, but some long-term complications of the liver and kidney remain. Gene therapy for GSD-Ib is less advanced than for GSD-Ia and only transient correction of myeloid dysfunction has been achieved. A question remains as to whether a single rAAV vector can meet the expression efficiency and tropism required to treat all aspects of GSD-I, or if a multi-pronged approach is needed. An understanding of the strengths and weaknesses of rAAV vectors in the context of strategies to achieve efficient transduction of the liver, kidney and hematopoietic stem cells is required for treating GSD-I.     

1个糖原累积症家系的分子诊断与产前诊断

目的对1个糖原累积症(glycogen storage disease,GSD)家系进行基因突变分析,并对该家系中的一高危胎儿进行产前分子诊断。方法采集该家系先证者及其父母外周血,采用二代测序方法查找先证者致病基因及突变位点,Sanger测序进行突变验证。确定先证者及其父母基因型后采集羊水标本,采用PCR扩增及直接测序方法进行产前分子诊断。结果该家系先证者为G6PC基因c.648GT纯合突变。双亲均为G6PC基因c.648GT杂合突变。胎儿携带与父母相同的c.648GT杂合突变。结论建立了对GSD进行分子诊断和产前分子诊断的方法,并成功应用于1个GSD家系。     

1例婴儿糖原贮积病Ⅳ型临床分析并文献复习

糖原贮积病(glycogen storage disease,GSD)Ⅳ型是一种罕见的常染色体隐性遗传病。本文报告了1例先天性GSDⅣ神经肌肉型患儿,伴有张力减退,出生时即有关节症状,5个月时发现肝酶升高,心脏和呼吸系统无异常;肌电图检查提示肌源性损害的可能性大。肝脏穿刺活检结果显示:广泛肝细胞变性伴包涵体以及桥状纤维化,符合GSDⅣ型;基因检测结果显示患儿GBE1基因存在2处错义突变:c.475C>T,p.Pro159Leu和c.1229T>G,p.Ile410Arg,为复合杂合突变,父母为携带者。截至2018年12月,共检索到相关外文文献16篇,中文文献6篇。迄今全球已报道的GSDⅣ型共61例,其中肝型22例,神经肌肉型39例,国内报道了13例,全部为肝型。神经肌肉型临床表现个体差异明显。本例是中国首次报道的GSDⅣ型神经肌肉型患者。     

Lipid-storage myopathy with glycogen storage disease gene mutations mimicking polymyositis: a case report and review of the literature

A 26-year-old Asian woman with persistent muscle weakness was diagnosed with polymyositis based on biopsy findings at another hospital 11 years ago. However, her symptoms fluctuated repeatedly under treatment with prednisone and immunosuppressive agents, and worsened 2 months prior to the current presentation. A second muscle biopsy suggested metabolic myopathy, and genetic testing revealed a novel c.1074C > T variant in the glycogen synthase 1 gene (GYS1), which is implicated in muscle glycogen storage disease type 0. However, no abnormalities in glycogen deposition were found by biopsy; rather, muscle fibers exhibited large intracellular lipid droplets. Furthermore, muscle strength was greatly restored and circulating levels of creatine kinase indicative of muscle degeneration greatly reduced by vitamin B2 treatment. Therefore, the final diagnosis was lipid storage myopathy.     

Early, sustained efficacy of adeno-associated virus vector-mediated gene therapy in glycogen storage disease type Ia

The deficiency of glucose-6-phosphatase (G6Pase) underlies life-threatening hypoglycemia and growth retardation in glycogen storage disease type Ia (GSD-Ia). An adeno-associated virus (AAV) vector encoding G6Pase was pseudotyped as AAV8 and administered to 2-week-old GSD-Ia mice (n = 9). Median survival was prolonged to 7 months following vector administration, in contrast to untreated GSD-Ia mice that survived for only 2 weeks. Although GSD-Ia mice were initially growth-retarded, treated mice increased fourfold in weight to normal size. Blood glucose was partially corrected by 2 weeks following treatment, whereas blood cholesterol normalized. Glucose-6-phosphatase activity was partially corrected to 25% of the normal level at 7 months of age in treated mice, and blood glucose during fasting remained lower in treated, affected mice than in normal mice. Glycogen storage was partially corrected in the liver by 2 weeks following treatment, but reaccumulated to pre-treatment levels by 7 months old (m.o.). Vector genome DNA decreased between 3 days and 3 weeks in the liver following vector administration, mainly through the loss of single-stranded genomes; however, double-stranded vector genomes were more stable. Although CD8+ lymphocytic infiltrates were present in the liver, partial biochemical correction was sustained at 7 m.o. The development of efficacious AAV vector-mediated gene therapy could significantly reduce the impact of long-term complications in GSD-Ia, including hypoglycemia, hyperlipidemia and growth failure.