Diphthamide-deficiency syndrome: a novel human developmental disorder and ribosomopathy.

We describe a novel type of ribosomopathy that is defined by deficiency in diphthamidylation of translation elongation factor 2. The ribosomopathy was identified by correlating phenotypes and biochemical properties of previously described patients with diphthamide biosynthesis gene 1 (DPH1) deficiencies with a new patient that carried inactivating mutations in both alleles of the human diphthamide biosynthesis gene 2 (DPH2). The human DPH1 syndrome is an autosomal recessive disorder associated with developmental delay, abnormal head circumference (microcephaly or macrocephaly), short stature, and congenital heart disease.