Abstract
Congenital disorders of glycosylation (CDG) are genetic diseases caused by abnormal protein and lipid glycosylation. In this chapter, we report the clinical, biochemical, and molecular findings in two siblings with an unidentified CDG (CDG-Ix). They are the first and the third child of healthy consanguineous Argentinean parents. Patient 1 is now a 11-year-old girl, and patient 2 died at the age of 4 months. Their clinical picture involved liver dysfunction in the neonatal period, psychomotor retardation, microcephaly, seizures, axial hypotonia, feeding difficulties, and hepatomegaly. Patient 1 also developed strabismus and cataract. They showed a type 1 pattern of serum sialotransferrin. Enzymatic analysis for phosphomannomutase and phosphomannose isomerase in leukocytes and fibroblasts excluded PMM2-CDG and MPI-CDG. Lipid-linked oligosaccharide (LLO) analysis showed a normal profile. Therefore, this result could point to a deficiency in the dolichol metabolism. In this context, ALG8-CDG, DPAGT1-CDG, and SRD5A3-CDG were analyzed and no defects were identified. In conclusion, we could not identify the genetic deficiency in these patients yet. Further studies are underway to identify the basic defect in them, taking into account the new CDG types that have been recently described.
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- CDG:
-
Congenital disorder of glycosylation
- COG:
-
Oligomeric golgi complex
- HPLC:
-
High-performance liquid chromatography
- IEF:
-
Isoelectrofocusing
- MS:
-
Mass spectrometry
- Tf:
-
Transferrin
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Acknowledgments
The authors are grateful to Liesbeth Keldermans from the Center for Human Genetics and Sandra Van Aerschot from the Center for Metabolic Diseases for DNA analysis and capillary zone electrophoresis. The authors would like to thank Dr. Paz Briones, Dr. Rafaél Artuch, and Dr. María Antonia Vilaseca from Barcelona (Spain). At CEMECO, this work was supported by grants from CONICET (PIP6338), FONCyT – BID PICT2350, Catholic University of Córdoba, and Argentinean National Health Ministry.
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Synopsis
This is a report of the clinical, biochemical, and molecular studies of two siblings characterized as CDG-Ix, identified in the context of a new program for the systematic identification of CDG in Argentina.
Author’s Contributions
MBBM was responsible for preparative studies in terms of isoelectrofocusing, HPLC, CDG enzymatic assays, molecular studies, data gathering, and development of the manuscript.
AD and NA contributed in the biochemical studies.
NG is a physician specialized in metabolic disease who works at CEMECO.
LS and DG contributed in the mass spectrometry analysis.
GM was responsible for the molecular studies and contributed in the development and final draft of the manuscript.
JJ provided specialized opinion in the clinical diagnosis. He contributed in the development and final draft of the manuscript.
RDK provided specialized opinion and was responsible for the evaluation and the follow-up of the patient. She coordinates the research in metabolic diseases in the Center for Study of Congenital Metabolopaties (CEMECO).
CGA is responsible for the research, conceived the idea for the chapter, and contributed to the development and final draft of the manuscript. She coordinated the CDG research program in CEMECO.
Competing Interest Statement
All authors confirm that they have no competing interests for declaration. The authors confirm independence from the sponsors. They did not receive any outside funding or grants in support of their research.
Details of Funding
This work was supported by grants from CONICET (PIP6338), (ANCyT-FONCyT) PICT2350, Catholic University of Córdoba, and Argentinean National Health Ministry. All authors confirm that they have no competing interests for declaration. The authors confirm independence from the sponsors; the content of the chapter has not been influenced by the sponsors.
Details of Ethics Approval
Written consent was obtained from the patients and their parents to participate in this study, and they allow us to submit this manuscript with images for the publication. A copy of written consent is available for review. The study was approved by the Ethics Committee of the Children’s Hospital of Córdoba (CIEIS) Act Nº 95/2007. All studies were carried out in accordance with the Word Medical Association Declaration of Helsinki.
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Millón, M.B.B. et al. (2011). Two Argentinean Siblings with CDG-Ix: A Novel Type of Congenital Disorder of Glycosylation?. In: JIMD Reports - Case and Research Reports, 2011/1. JIMD Reports, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_18
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DOI: https://doi.org/10.1007/8904_2011_18
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