Two Argentinean Siblings with CDG-Ix: A Novel Type of Congenital Disorder of Glycosylation?

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.

Mass spectrometry glycophenotype characterization of ALG2-CDG in Argentinean patients with a new genetic variant in homozygosis

“…CDG screening was applied in all suspected patients referred by pediatricians to the Center for the Study of Con genital Metabolopathie s (CEMECO) at t he Children's Hospital in Córdoba. Suspected patients presented a multisystem phenotype and the main clinical manifestations were mild to severe psychomotor disability, hypotonia, seizures, failure to thrive, hormonal anomalies, coagulopathy, and cerebellar hypoplasia [12,24]. Ethical permissions and informed consents were obtained from the institutional review boards of CIEIS-Ethics Committee, Children's Hospital of Córdoba, Argentina.…”

“…Serum transferrin was purified by immunoaffinity depletion with IgY antibody cartridges (Seppro™ GenWay Biotech, San Diego, CA, USA). Glycoforms of transferrin were analyzed by automated isoelectric focusing (Tf-IEF) according to standard procedures [12,13,24].…”

Epileptic spasms in congenital disorders of glycosylation

“…Seizures began later, at the age of 18 months, and consisted of tonic and tonic-clonic seizures, as well as sudden massive jerks, presenting as a combination of myoclonus and spasm. So far, 25 patients with CDG Ix have been described (Morava et al, 2008, Millón et al, 2011, presenting very heterogeneous clinical features. Epilepsy is reported in seven of them, but seizure types and EEG features are not detailed.…”