Dolichol kinase deficiency (DOLK‐CDG): Two new cases and expansion of phenotype

摘要

Congenital disorders of glycosylation (CDGs) are a group of genetic diseases caused by mutations in genes that are necessary for the addition of oligosaccharides to acceptor proteins or lipids. An early step in this process requires dolichol kinase (DK) to catalyze the formation of dolichyl phosphate, which acts as a membrane anchor for initial attachment of sugar residues that are subsequently built up to oligosaccharides and transferred to acceptor proteins and lipids for further processing. Biallelic mutations in DOLK , the gene for DK, result in human in a CDG with variable symptoms, ranging from nonsyndromic dilated cardiomypopathy to severe multiorgan involvement. We report two female siblings with novel compound heterozygous mutations in DOLK : c.951CA (p.Tyr317Ter) and c.1558AG (p.Thr520Ala). Both patients presented in the neonatal period with severe ichthyosis, unusual distal digital constrictions and dilated cardiomyopathy which resulted in death. Histology of the skin showed lipid droplet accumulation in the stratum corneum and keratinocytes, which suggests defective epidermal lipid metabolism. These patients represent an earlier and more severe form of DOLK‐CDG (CDG‐1m) with a striking presentation at birth that expands the known phenotypic spectrum.