迟发型甲基丙二酸血症6例报道并文献复习

正甲基丙二酸血症(methylmalonic acidemia,MMA)或称甲基丙二酸尿症(methylmalonic aciduria,MMA)是先天性有机酸代谢异常中最常见的疾病,为常染色体隐性遗传。临床上有单纯性甲基丙二酸血症(MMA)和甲基丙二酸血症合并同型半胱氨酸尿症(MMA-HC)两种类型。由于甲基丙二酰辅酶A变位酶或其辅酶钴胺素(维生素B12)代谢缺陷导     

以小脑损害为主要表现的成人甲基丙二酸血症合并高同型半胱氨酸血症一例

报告1例成年起病的甲基丙二酸血症合并高同型半胱氨酸血症患者的临床资料。患者为男性,24岁发病,以行走不稳、精神行为异常起病,进行性加重,神经系统体检发现明显的小脑性共济失调及锥体束征,头颅磁共振成像显示双侧小脑半球对称性长T2信号,血液总同型半胱氨酸、尿甲基丙二酸水平显著增高,基因检测发现MMACHC基因复合杂合突变c.482G>A及c.217C>T,确诊为钴胺素C缺乏症。经给予腺苷钴胺、甜菜碱、叶酸、左卡尼汀治疗后患者行走不稳略有所好转,血同型半胱氨酸水平也显著下降。     

晚发型cblC型甲基丙二酸尿症合并同型半胱氨酸血症1例报告并文献复习

目的 探讨晚发型甲基丙二酸尿症合并同型半胱氨酸血症的临床及基因变异特点。方法 回顾性分析1例MMACHC基因突变致晚发型cblC型甲基丙二酸尿症合并同型半胱氨酸血症患者的临床资料及基因检测结果，并结合文献讨论。结果 本例男性患者，以双足麻木起病，逐渐出现双下肢僵硬无力，发病前有非特异性精神行为异常症状，此次就诊经基因检测发现MMACHC基因4号外显子存在c. 482G>A(p. Arg161Gln)错义突变，与文献报道c. 482G>A复合杂合突变不同，本例患者突变类型为纯合突变。结论 甲基丙二酸尿症合并同型半胱氨酸血症的临床异质性较大，容易漏诊误诊，当出现不明原因的精神行为异常时应考虑该诊断，基因检测是诊断的重要依据，同时也可指导该病的分型。     

以周围神经损伤为主的晚发型甲基丙二酸血症合并同型半胱氨酸血症1例

<正>甲基丙二酸血症(MMA)又称甲基丙二酸尿症,是一种常染色体隐性遗传代谢病。MMA患者根据发病年龄可分为早发型和晚发型[1],以早发型多见。MMA合并同型半胱氨酸血症临床表型复杂[2],可以导致多系统受累,以CNS损害为主,引起智力下降、运动功能障碍、癫痫及锥体外系症状,周围神经损伤较为少见。关于以周围神经损伤为主的MMA合并同型半胱氨酸血症的病例,临床诊断困难,国内外仅有个别报道。     

甲基丙二酸血症合并高同型半胱氨酸血症的临床特点(附1例报告)

目的 探讨甲基丙二酸血症(MMA)合并高同型半胱氨酸血症的临床特点.方法 回顾性分析1例MMA合并高同型半胱氨酸血症患者的临床资料,并进行复习文献.结果 患者女性,30岁,临床表现为双下肢麻木无力.尿甲基丙二酸、血丙酰基肉碱与乙酰基肉碱的比值(C3/C2)、血同型半胱氨酸均升高;基因检测发现MMACHC基因存在c.60...     

高同型半胱氨酸血症及相关因子与脑梗死相关性的研究

目的 :研究高同型半胱氨酸血症及N5N10 亚甲基四氢叶酸还原酶 (methylenetetrahydrofolatereductase ,MTHFR)基因、叶酸和维生素B12 与脑梗死的关系。方法 :PCR RFLP技术检测 5 4例脑梗死患者及 3 0例对照的MTHFR基因型 ;高效液相色谱法测定空腹及蛋氨酸负荷后血浆tHcy水平 ;化学发光法测定血清叶酸和维生素B12 浓度。结果 :患者组中MTHFR基因T/T型及T等位基因频率、空腹及负荷后tHcy水平显著高于对照组 ;而血清叶酸和维生素B12 水平低于对照组。结论 :MTHFR基于突变、高同型半胱氨酸血症及叶酸、维生素B12 缺乏与脑卒中发病有关。     

MTHFR基因多态性在高同型半胱氨酸 血症患者中的分布特点

目的 了解高同型半胱氨酸血症患者中MTHFR基因多态性的分布特点。方法 筛选本院住院患者中高同型半胱氨酸血症患者213例,同时检测亚甲基四氢叶酸还原酶(MTHFR)的C677T位点及血清叶酸及维生素B12水平,根据相关基因酶活性分为高代谢(CC)、中等代谢(CT)、低代谢(TT)。结果(1)高同型半胱氨酸血症患者中CC发生率为24.4%、CT发生率为30.1%、TT发生率为45.5%;(2)高同型半胱氨酸血症患者中叶酸水平降低发生率为12.2%、维生素B12水平降低发生率为8.4%、二者同时水平降低发生率为7.0%。结论 高同型半胱氨酸血症患者中低代谢发生率高,同时多合并叶酸和/或维生素B12水平降低。     

成人型钴胺素C缺陷病的临床特点

目的 探讨成人型钴胺素C缺陷病的临床特点。方法 报道1例成人型钴胺素C缺陷病患者,通过中国知网、Pubmed数据库检索初次发表至2021年10月报道的成人型钴胺素C缺陷病患者相关文献,并对该病进行总结。结果 本研究最终纳入英文文献10篇,中文文献5篇,加上本例共计22例患者。患者最常见的5种临床表现包括运动障碍(14/22,63.64%)、认知障碍(13/22,59.09%)、情绪低落(9/22,40.91%)、共济失调(8/22,36.36%)、自主神经功能障碍(7/22,31.82%)。最常见的3种并发症为肾功能不全(5/22,22.73%)、贫血(4/22,18.18%)、癫痫(3/22,13.64%)。实验室检查中发现11例患者存在高同型半胱氨酸血症合并甲基丙二酸血症(11/22,50.00%),发现高同型半胱氨酸血症合并甲基丙二酸尿症患者10例(45.45%),单独表现为高同型半胱氨酸血症患者1例(4.55%)。在8例行血氨基酸和酰基肉碱串联质谱检测的患者中,均发现血丙酰肉碱及丙酰肉碱与乙酰肉碱比值增高。在治疗方面,21例患者使用维生素B₁₂补充治疗,其...     

维生素B_（12）联合叶酸治疗高同型半胱氨酸血症疗效观察

目的观察维生素B12联合叶酸治疗高同型半胱氨酸血症的疗效。方法入选106例,随机分为治疗组54例,对照组52例。对照组给予阿斯匹林100mg口服,1次/d,疗程4周;治疗组在对照组基础上给予维生素B12联合叶酸片,3次/d,疗程8周。治疗前后分别测定血浆同型半胱氨酸浓度。结果治疗组血浆半胱氨酸浓度较对照组有明显改善,差异有统计学意义（P〈0.05）。结论维生素B12联合叶酸片能有效降低血浆同型半胱氨酸水平,有临床应用价值。     

维生素B12联合叶酸治疗高同型半胱氨酸血症疗效观察

目的观察维生素B12联合叶酸治疗高同型半胱氨酸血症的疗效。方法入选106例,随机分为治疗组54例,对照组52例。对照组给予阿斯匹林100mg口服,1次/d,疗程4周;治疗组在对照组基础上给予维生素B12联合叶酸片,3次/d,疗程8周。治疗前后分别测定血浆同型半胱氨酸浓度。结果治疗组血浆半胱氨酸浓度较对照组有明显改善,差异有统计学意义(P<0.05)。结论维生素B12联合叶酸片能有效降低血浆同型半胱氨酸水平,有临床应用价值。     

维生素B_(12)依赖型甲基丙二酸血症一家系临床表型和基因突变分析及疗效评价

目的探讨维生素B_(12)依赖型甲基丙二酸血症家系临床特点、基因突变和维生素B_(12)治疗效果。方法采集一维生素B_(12)依赖型甲基丙二酸血症家系共4名成员临床资料,抽取外周静脉血行血浆氨基酸和酰基肉碱谱分析及基因检测,评价维生素B_(12)治疗效果。结果家系中先证者12岁发病,以学习成绩下降、性格改变为首发症状,病程中出现幻觉、双下肢无力;先证者之弟主要表现为易怒、学习成绩较差。经血浆氨基酸和酰基肉碱谱分析,先证者及其弟血浆丙酰肉碱、丙酰肉碱/乙酰肉碱比值升高,尿液甲基丙二酸水平升高。基因检测显示,先证者及其弟均存在MMACHC基因复合杂合突变c.482GA(p.Arg161Gln)和c.609GA(p.Trp203X),其父携带MMACHC基因错义突变c.482GA(p.Arg161Gln),其母携带MMACHC基因无义突变c.609GA(p.Trp203X)。经维生素B_(12)治疗后均症状好转。结论晚发型维生素B_(12)依赖型甲基丙二酸血症系MMACHC基因复合杂合突变所致,维生素B_(12)治疗反应良好,早期诊断、及时治疗对患者预后意义重大。     

Neuropsychiatric disturbances in presumed late-onset cobalamin C disease

BACKGROUND: Combined methylmalonic aciduria and homocystinuria cobalamin C type (cobalamin C disease) is an inborn metabolic disorder consisting of an impaired intracellular synthesis of the 2 active forms of vitamin B12 (cobalamin), namely, adenosylcobalamin and methylcobalamin, that results in increased levels of methylmalonic acid and homocysteine in the blood and urine. Most patients present in the first year of life with systemic, hematological, and neurological abnormalities. Late-onset forms are rare and had not been comprehensively characterized. They could be easily misdiagnosed. OBJECTIVE: To describe clinical and biochemical features of the disease in 2 siblings affected with presumed late-onset cobalamin C disease. DESIGN: Case report and review of the literature. SETTING: Neurological intensive care unit of a university hospital. OBSERVATION: We describe 2 patients with neurological deterioration due to presumed cobalamin C disease. A 16-year-old girl was initially seen with psychosis and severe progressive neuropathy requiring mechanical ventilatory support and her 24-year-old sister had a 2-year disease course of subacute combined degeneration of the spinal cord. A metabolic workup displayed increased methylmalonic acid levels, severe hyperhomocysteinemia, and low plasma methionine levels. The diagnosis was then confirmed by demonstration of impaired synthesis of adenosylcobalamin and methylcobalamin in cultured skin fibroblasts and Epstein-Barr virus-infected lymphocytes. Under specific treatment the younger sister's condition dramatically improved. CONCLUSIONS: Although complementation studies have not been conducted, it is most likely these patients had cobalamin C disease. This study emphasizes the possibility of late-onset disease with purely neurological manifestations. Left untreated, this treatable condition can lead to death or irreversible damage to the nervous system. Screening for intracellular vitamin B12 dysmetabolism should, therefore, be considered in the investigation of adults with unexplained neurological disease, particularly when they are initially seen with a clinical picture suggestive of vitamin B12 deficiency.     

无脑白质影像学改变的晚发婴儿型异染性脑白质营养不良

目的 分析3例脑白质影像学无改变的晚发婴儿型异染性脑白质营养不良患儿的临床、电生理、影像学和病理学改变特点，总结其特征表现和诊断规律。方法 3例均为男性婴儿，月龄分别为20个月、27个月和28个月。均于出生后15～21个月出现运动发育停滞和倒退，以下肢运动障碍为主，表现有锥体束征。收入院后予以体格检查、电生理检查、头部MRI检查及腓肠神经活检。结果 （1）体格检查：例1双下肢肌力4级，肌张力降低；双膝腱反射亢进，双侧Babinski征阳性。例2四肢肌力5级，肌张力明显增高；腱反射亢进，双侧Babinski征阳性。例3眼球向左、右注视时可发现细小水平眼震，四肢肌力4级，肌张力低；四肢腱反射对称引出，双下肢病理征阴性。（2）辅助检查：3例患儿电生理检查均提示为周围神经病变，MRI检查无异常发现。（3）实验室检查：仅例1行外周血白细胞芳基硫酯酶A检查，显示活性显著下降。（4）腓肠神经活检：3例患儿均显示髓神经纤维显著减少，残存的有髓神经纤维的髓鞘变薄，甲苯胺蓝染色见部分雪旺细胞及吞噬细胞内出现紫红色异染颗粒，超微结构呈指纹样、髓样和平行排列的棒状结构。结论 病理检查证实细胞内沉积物具有异染性，而周围神经病变具有髓鞘发育不良特点。由于脑白质MRI无改变，这组以周围神经损害为主的息儿可能是异染性脑白质营养不良的一种特殊类型，诊断为伴有中枢神经系统损害的异染性周围神经病更符合临床表现规律。     

原发性侧索硬化的临床和影像学特征

目的 探讨胀发性侧索硬化（PLS）的临床和影像学特征。方法 对3例PLS患者的临床和影像学资料进行分析。结果 本组PLS患者女2例、男1例,均为缓慢起病。其中例1首发症状为右上肢僵硬、无力,例2为两下肢僵硬、无力,例3表观为假性延髓麻痹,随病情的进展,均出现四肢痉挛性瘫痪,肌力Ⅲ～Ⅳ级,肌张力呈折刀样增高,四肢腱反射亢进,两侧踝阵孪及Babinski征（＋）,头颅MRI T2 WI可见两侧内囊、大脑脚、运动区皮质及腑桥丛底部有异常高信号,^1H磁共振波谱（^1HMRS）示在病灶区有乙酰天门冬氨酸盐（NAA）降低及NAA／肌酸（Cr）比值降低。结论 PLS的临床症状、体征和MRI有特征性改变,^1HMRS的改变也有助于诊断。     

Extreme variability of phenotype in patients with an identical missense mutation in the lamin A/C gene: from congenital onset with severe phenotype to milder classic Emery-Dreifuss variant

BACKGROUND: Mutations of the LMNA gene, encoding the nuclear envelope proteins lamins A and C, have been associated with 7 distinct pathologic conditions. OBJECTIVE: To report 5 cases with the same missense mutation in exon 6 of the LMNA gene, resulting in an E358K substitution in the central rod domain. DESIGN: Case report. SETTING: Three muscle centers in England. PATIENTS: Five patients with missense mutations of the LMNA gene. RESULTS: All 5 individuals had muscle involvement, but the onset, severity, distribution of muscle weakness, and presence of associated features were highly variable. Three patients had humeroperoneal distribution of weakness and typical features of Emery-Dreifuss muscular dystrophy. Two other patients showed additional novel features. One had congenital onset and predominant axial weakness, with poor neck control and inability to sit independently at the age of 21 months. Another patient presented in childhood with an unusual pattern of muscle weakness, short stature, and midface hypoplasia with striking fat accumulation around the face and neck, in contrast to wasting of adipose tissue and muscle in the limbs. She developed both respiratory failure and cardiac arrhythmias in her late 20s. CONCLUSION: Our cases expand the clinical spectrum associated with mutations in the LMNA gene and further illustrate the overlapping phenotypes of the laminopathies.     

胸腺瘤副肿瘤综合征的临床特征——附4例报告

目的通过4例临床表现有一定意义的胸腺瘤副肿瘤综合征探讨其临床特征。方法收集并分析4例胸腺瘤副肿瘤综合征患者的检查结果,分析其诊疗经过。结果 4例胸腺瘤副肿瘤综合征患者中,3例以肌无力为主要表现,1例表现为少见的双下肢僵直,从双下肢僵直的临床表现角度看极其类似僵肢综合征,但肌电图无持续运动单位活动,其他检查结果也未见明显支持僵肢综合征诊断的证据,且该患者胸腺瘤切除术治疗效果明显。结论胸腺瘤副肿瘤综合征临床表现可多种多样,及时正确诊断对预后有积极影响。     

Cessation and resuming of alglucosidase alfa in Pompe disease: a retrospective analysis

Enzyme replacement therapy (ERT) with recombinant human alglucosidase alfa (rhGAA) in late-onset Pompe disease is moderately effective. Little is known about the clinical course after treatment termination and the resumption of ERT. In Switzerland, rhGAA therapy for Pompe disease was temporarily withdrawn after the federal court judged that the treatment costs were greatly out of proportion compared to the benefits. Re-treatment was initiated after the therapy was finally licensed. We retrospectively analysed seven Pompe patients, who underwent cessation and resumption of ERT (median age 43 years). The delay from first symptoms to final diagnosis ranged from 4 to 20 years. The demographics, clinical characteristics, assessments with the 6-min walking test (6-MWT), the predicted forced vital capacity (FVC) and muscle strength were analysed. Before initiation of ERT, all patients suffered from proximal muscle weakness of the lower limbs; one was wheelchair-bound and two patients received night-time non-invasive ventilation. Initial treatment stabilised respiratory function in most patients and improved their walking performance. After treatment cessation, upright FVC declined in most and the 6-MWT declined in all patients. Two patients needed additional non-invasive ventilatory support. Twelve months after resuming ERT, the respiratory and walking capacity improved again in most patients. However, aside for one patient, none of the patients reached the same level of respiratory function or distance walked in 6 min, as at the time of ERT withdrawal. We conclude that cessation of ERT in Pompe disease causes a decline in clinical function and should be avoided. Resuming treatment only partially recovers respiratory function and walking capacity.     

可逆性脑血管收缩综合征临床及影像学特点

目的探讨可逆性脑血管收缩综合征(RCVS)的临床、影像学特点,以提高对该病的认识。方法总结3例RCVS患者的临床及影像学资料并复习相关文献。结果本组3例患者均以剧烈头痛为首发症状,其中1例伴有双下肢无力,1例伴视物模糊、右侧肢体轻偏瘫。TCD检查均提示不同血管不同程度的血流速度增快,头颅MRI及MRA检查提示部分血管痉挛,典型者呈"串珠样"改变;2例脑内有病灶。脑脊液等相关检查无特异性,经钙离子拮抗剂等治疗后临床症状逐渐消失,1~7个月超声影像学复查完全恢复正常,临床呈单相病程,预后良好。结论临床表现为"雷击样、撕裂样"头痛的患者伴或不伴有神经系统定位体征,影像学检查有血管痉挛表现,在排除其他疾病后应考虑RCVS的可能。     

Cerebrospinal fluid methylmalonic acid concentrations in neurological patients with low and normal serum cobalamin concentrations

Objective – To determine whether cerebrospinal fluid (CSF) methylmalonic acid (MMA) is increased in neurological patients with low serum cobalamin (Cbl, vitamin B₁₂) concentrations as opposed to neurological patients with normal serum Cbl concentrations. Material and methods – We measured MMA concentrations in serum and CSF of neurological patients with low serum cobalamin concentrations, but without overt cobalamin related manifestations such as anemia or combined disease of the cord, and neurological patients with normal serum cobalamin concentrations (controls). Results – Serum and CSF MMA concentrations were significantly higher in patients than in controls. Serum MMA was elevated in 4 patients of whom 3 had clearly elevated CSF MMA concentrations. Conclusion – Strong indications for cobalamin deficiency can be found not only in serum but also in CSF of patients with seemingly asymptomatic low serum cobalamin concentrations.