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Mild Clinical and Biochemical Phenotype in Two Patients with PMM2-CDG (Congenital Disorder of Glycosylation Ia)

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Abstract

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.

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Acknowledgments

This work was supported by grants from the Fondo de Investigación Sanitaria (FIS PI080663, PI080307, and PI10/00455). The CIBERER is an initiative of the Instituto de Salud Carlos III (ISCIII, MICIN, Spain). R.Artuch and M. Casado are supported by the program Intensificacion de la Actividad Investigadora (ISCIII). R Montero and MM O’Callaghan were funded by the CIBERER.

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Authors and Affiliations

  1. Clinical Biochemistry, Hospital Sant Joan de Déu, Barcelona, Spain

    M. Casado, R. Montero & R. Artuch

  2. Pediatric Neurology and Radiology Departments, Hospital Sant Joan de Déu, Barcelona, Spain

    M. M. O’Callaghan, J. Muchart, A. Aracil & M. Pineda

  3. Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, Barcelona, Spain

    M. M. O’Callaghan, R. Montero, C. Pérez-Cerda, B. Pérez, P. Briones, M. Pineda & R. Artuch

  4. Centro de Diagnóstico de Enfermedades Moleculares, Centro de Biología Molecular Severo Ochoa, UAM-CSIC, Universidad Autónoma de Madrid, and CIBERER, Madrid, Spain

    C. Pérez-Cerda & B. Pérez

  5. Secció d’Errors Congènits del Metabolisme, Hospital Clínic, CSIC and CIBERER, Barcelona, Spain

    P. Briones & E. Quintana

  6. Department of Biochemistry and Molecular Biology, Universidad Autónoma of Barcelona, Barcelona, Spain

    M. Casado

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  1. M. Casado
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  2. M. M. O’Callaghan
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  7. E. Quintana
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  11. R. Artuch
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Correspondence to R. Artuch.

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Casado, M., O’Callaghan, M.M., Montero, R. et al. Mild Clinical and Biochemical Phenotype in Two Patients with PMM2-CDG (Congenital Disorder of Glycosylation Ia). Cerebellum 11, 557–563 (2012). https://doi.org/10.1007/s12311-011-0313-y

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  • DOI: https://doi.org/10.1007/s12311-011-0313-y

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