Clinical Biochemistry, Hospital Sant Joan de Déu, Barcelona, Spain.
Cerebellum. 2012 Jun;11(2):557-63. doi: 10.1007/s12311-011-0313-y.
Phosphomannomutase 2 deficiency (PMM2-CDG) patients may present as mild phenotypes, with the cerebellum frequently involved. In those cases, false-negative results in screening may occur when applying conventional biochemical procedures. Our aim was to report two patients with a diagnosis of PMM2-CDG presenting with mild clinical phenotype. Patient 1-at 9 months of age, she presented with just psychomotor delay, tremor, hypotonia, and slight lipodystrophy. Patient 2-she presented at 8 months of age with psychomotor delay, hand stereotypes, hypotonia, convergent bilateral strabismus, and tremor but no lipodystrophy. Routine biochemical parameters including blood count, clotting factors, proteins, and thyroid hormone were normal in both cases. Cranial MRI evidenced mild cerebellar atrophy with moderate vermis hypoplasia. In case 1, sialotransferrin pattern showed very slightly increased disialotransferrin with no asialotransferrin, and in case 2, the transferrin pattern was impaired in the first study but nearly normal in the second. Nevertheless, in all the samples, quantification of the patterns obtained by capillary zone electrophoresis analysis gave results out of the control range. High residual PMM2 activity was observed in both cases and the genetic analysis showed that patient 1 was heterozygous for c.722G>C (p.C241S) and c.368G>A (p.R123Q) mutations, and patient 2 showed the c.722G>C and the c.470T>C (p.F157S) mutations in the PMM2 gene. We would like to stress the importance of the use of sensitive semiquantitative methods of screening for CDG in order to achieve early identification of patients with mild phenotypes. Intentional tremor was an atypical but remarkable clinical feature in both cases, and the global cerebellar atrophy with vermis hypoplasia reinforced the early clinical suspicion of a PMM2-CDG disease.
磷酸甘露糖变位酶 2 缺乏症（PMM2-CDG）患者可能表现为轻度表型，小脑常受累。在这种情况下，应用常规生化程序进行筛查时可能出现假阴性结果。我们的目的是报告 2 例以轻度临床表现为特征的 PMM2-CDG 患者。患者 1-在 9 个月大时，仅表现为精神运动发育迟缓、震颤、肌张力低下和轻微的脂肪营养不良。患者 2-她在 8 个月大时表现为精神运动发育迟缓、手刻板动作、肌张力低下、双侧内斜视和震颤，但无脂肪营养不良。血常规、凝血因子、蛋白和甲状腺激素等常规生化参数在两种情况下均正常。头颅 MRI 显示小脑轻度萎缩，蚓部中度发育不良。在病例 1 中，唾液转铁蛋白模式显示双涎酸转铁蛋白略有增加，无涎酸转铁蛋白，而在病例 2 中，转铁蛋白模式在第一次研究中受损，但在第二次研究中几乎正常。然而，在所有样本中，毛细管区带电泳分析获得的模式定量结果均超出了正常范围。在两种情况下均观察到 PMM2 活性的高残留，基因分析显示患者 1 为杂合子 c.722G>C(p.C241S)和 c.368G>A(p.R123Q)突变，患者 2 为 PMM2 基因中的 c.722G>C 和 c.470T>C(p.F157S)突变。我们想强调的是，为了实现对轻度表型患者的早期识别，使用敏感的半定量筛查 CDG 方法的重要性。意向性震颤是这两种情况下都具有非典型但显著的临床特征，而小脑的全脑萎缩和蚓部发育不良则强化了对 PMM2-CDG 疾病的早期临床怀疑。
