Conditions associated with a defect in N-glycosylation:
The clinical features differ between the subtypes. The disorders may affect
the head and neck (prominent forehead, large ears, strabismus, nystagmus,
myopia, retinopathy pigmentosa, flat nasal bridge, thin upper lip, cleft
palate), heart (hypertrophic obstructive cardiomyopathy, cardiac failure,
exudative pericarditis, pericardial effusions), blood (prolonged prothrombin
time, factor XI deficiency, antithrombin III deficiency, thrombocytosis,
platelet hyperaggregability, neutrophil dysfunction, decreased levels of
immunoglobulins A and G), central nervous system (psychomotor retardation,
generalized hypotonia, cerebral and cerebellar abnormalities, ataxia,
hyporeflexia, seizures, stroke-like episodes, olivopontine hypoplasia,
Dandy-Walker Syndrome, peripheral neuropathy), skin (orange-peel skin, fat
pads, inverted nipples, erythematous changes), endocrine system
(hypothyroidism, hypogonadism), liver and gastrointestinal tract (hepatic
fibrosis/cirrhosis, hepatomegaly, hypalbuminemia, ascites, failure to
thrive, intestinal lymphangiectases, small bowel villous atrophy, abnormal
intestinal permeability and enterocyte lipid transport, associated with
abnormal glycosylation of intestinal glycoproteins, diarrhea, vomiting), and
kidneys (renal cysts, proximal tubulopathy, nephritic syndrome). Other
features include pleural effusions, osteopenia, recurrent fractures,
kyphosis, dystrophic limbs, weakness, and joint contractures. The clinical
picture of CDG type Ib differs markedly from the other forms of CDG,
presenting as a protein-losing enteropathy, hyperinsulinemic hypoglycemia,
and thrombosis or bleeding disorder. Generalized hypotonia is the only
neurologic abnormality in CDG type Ib. Mannose substitution in these
patients is an effective treatment. Death in early infancy has been
described in a few patients with CDG.