Congenital disorders of glycosylation are a growing group of inborn errors of protein glycosylation. Cardiac involvement is frequently observed in the most common form,
PMM2-CDG, especially
hypertrophic cardiomyopathy.
Dilated cardiomyopathy, however, has been only observed in a few CDG subtypes, usually with a lethal outcome. We report on cardiac pathology in nine patients from three unrelated Israeli families, diagnosed with
dolichol kinase deficiency, due to novel, homozygous DK1 gene mutations. The cardiac symptoms varied from discrete, mild dilation to overt
heart failure with death. Two children died unexpectedly with acute symptoms of
heart failure before the diagnosis of DK1-CDG and
heart transplantation could take place. Three other affected children with mild
dilated cardiomyopathy at the time of the diagnosis deteriorated rapidly, two of them within days after an acute
infection. They all went through successful
heart transplantation; one died unexpectedly and 2 others are currently (after 1-5 years) clinically stable. The other 4 children diagnosed with mild
dilated cardiomyopathy are doing well on supportive
heart failure therapy. In most cases, the cardiac findings dominated the clinical picture, without central nervous system or multisystem involvement, which is unique in CDG syndrome. We suggest to test for DK1-CDG in patients with
dilated cardiomyopathy. Patients with discrete
cardiomyopathy may remain stable on supportive treatment while others deteriorate rapidly. Our paper is the first comprehensive study on the phenotype of DK1-CDG and the first successful
organ transplantation in CDG syndrome.