Carbohydrate-deficient glycoprotein syndrome (CDGs) type I are genetic multisystem disorders characterized by abnormal cathodal isoforms of serum transferrin (increased di- and asialo-transferrin), and deficient phosphomannomutase (PMM) activity in the majority of patients.
We report here a novel CDGs variant with milder clinical phenotype and profound deficiency of phosphomannose isomerase (PMI) in fibroblasts.
BA was born at term from nonconsanguineous parents. At age 6 weeks he was hospitalized for recurrent vomiting and poor weight gain. Clinical examination showed lipodistrophy, modest hepatomegaly, and generalized hypotonia. Laboratory investigations revealed disturbed liver function (>ASAT, ALAT, ALP, bilirubin; < CHE, albumin), megaloblastic anemia, and reduced antithrombin III and TBG. Transferrin isoelectrofocusing showed a typical CDGs type I pattern. At 4 m, brain CT scan showed diffuse and marked white matter hypodensity with normal cerebellum.
Remarkably, when solid foods (vegetables, rice, meat, fruits) were added to exclusive breast feeding at age 4 m, the child stopped vomiting, started to gain weight, and normalized muscle tone within a few months. Laboratory abnormalities, serum transferrin isoelectrofocusing and neuroimaging paralleled the clinical course with complete normalization at age 10 m.
A deficiency of PMI (0.2 mU/mg protein; controls 8.0+2.0) was found in cultured fibroblasts, while PMM showed normal activity.
This child, with typical CDGs type I sialotransferrin pattern and profound PMI deficiency, showed a milder phenotype with predominant enterohepatic symptoms. A defect of PMI, which catalyzes the first step of mannose pathway, compromises protein N-glycosilation. However, we hypothesize that the higher mannose content of solid foods, compeared to human milk, was a very efficient therapy for this child. This would be due to the possibility of bypassing the PMI step and forming mannose 6-phosphate through the action of hexokinase directly by mannose from food or from the catabolism of endogenous glycoprotein.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dionisi-Vici, C., Bartuli, A., Bertini, E. et al. Phosphomannose Isomerase Deficiency: a novel, potentially treatable CDG syndrome variant • 709. Pediatr Res 43 (Suppl 4), 123 (1998). https://doi.org/10.1203/00006450-199804001-00730
Issue Date:
DOI: https://doi.org/10.1203/00006450-199804001-00730