Fischer Sabine, Huemer Martina, Baumgartner Matthias, Deodato Federica, Ballhausen Diana, Boneh Avihu, Burlina Alberto B, Cerone Roberto, Garcia Paula, Gökçay Gülden, Grünewald Stephanie, Häberle Johannes, Jaeken Jaak, Ketteridge David, Lindner Martin, Mandel Hanna, Martinelli Diego, Martins Esmeralda G, Schwab Karl O, Gruenert Sarah C, Schwahn Bernd C, Sztriha László, Tomaske Maren, Trefz Friedrich, Vilarinho Laura, Rosenblatt David S, Fowler Brian, Dionisi-Vici Carlo
University Children's Hospital Basel, Spitalstrasse 33, Basel, 4506, Switzerland.
J Inherit Metab Dis. 2014 Sep;37(5):831-40. doi: 10.1007/s10545-014-9687-6. Epub 2014 Mar 6.
The cblC defect is the most common inborn error of vitamin B12 metabolism. Despite therapeutic measures, the long-term outcome is often unsatisfactory. This retrospective multicentre study evaluates clinical, biochemical and genetic findings in 88 cblC patients. The questionnaire designed for the study evaluates clinical and biochemical features at both initial presentation and during follow up. Also the development of severity scores allows investigation of individual disease load, statistical evaluation of parameters between the different age of presentation groups, as well as a search for correlations between clinical endpoints and potential modifying factors.
No major differences were found between neonatal and early onset patients so that these groups were combined as an infantile-onset group representing 88 % of all cases. Hypotonia, lethargy, feeding problems and developmental delay were predominant in this group, while late-onset patients frequently presented with psychiatric/behaviour problems and myelopathy. Plasma total homocysteine was higher and methionine lower in infantile-onset patients. Plasma methionine levels correlated with "overall impression" as judged by treating physicians. Physician's impression of patient's well-being correlated with assessed disease load. We confirmed the association between homozygosity for the c.271dupA mutation and infantile-onset but not between homozygosity for c.394C>T and late-onset. Patients were treated with parenteral hydroxocobalamin, betaine, folate/folinic acid and carnitine resulting in improvement of biochemical abnormalities, non-neurological signs and mortality. However the long-term neurological and ophthalmological outcome is not significantly influenced. In summary the survey points to the need for prospective studies in a large cohort using agreed treatment modalities and monitoring criteria.
cblC缺陷是维生素B12代谢最常见的先天性缺陷。尽管采取了治疗措施，但长期预后往往不尽人意。这项回顾性多中心研究评估了88例cblC患者的临床、生化和基因学发现。为该研究设计的问卷评估了初次就诊时和随访期间的临床和生化特征。此外，严重程度评分的制定有助于调查个体疾病负荷、对不同发病年龄组之间的参数进行统计学评估，以及寻找临床终点与潜在修正因素之间的相关性。
新生儿期和早发型患者之间未发现重大差异，因此将这些组合并为婴儿期发病组，占所有病例的88%。该组中肌张力减退、嗜睡、喂养问题和发育迟缓较为常见，而晚发型患者则经常出现精神/行为问题和脊髓病。婴儿期发病患者的血浆总同型半胱氨酸水平较高，蛋氨酸水平较低。血浆蛋氨酸水平与治疗医生判断的“总体印象”相关。医生对患者健康状况的印象与评估的疾病负荷相关。我们证实了c.271dupA突变纯合子与婴儿期发病之间的关联，但c.394C>T纯合子与晚发型之间无关联。患者接受了胃肠外羟钴胺、甜菜碱、叶酸/亚叶酸和肉碱治疗，生化异常、非神经体征和死亡率得到改善。然而，长期的神经和眼科预后并未受到显著影响。总之，该调查指出需要在大型队列中进行前瞻性研究，采用一致的治疗方式和监测标准。
