lysyl hydroxylase 3 deficiency
Definition An inherited connective tissue disorder (OMIM:612394) characterised by multiple severe congenital malformations involving COL2A1 and other collagen gene products, which affects many tissues and organs.
Pathogenesis The clinical manifestations are in keeping with a failure of lysyl hydroxylation and lack of addition of carbohydrates to hydroxylysyl groups, which affects many collagens.
Molecular pathology Defects of PLOD3, which encodes an enzyme* that hydroxylates lysyl residues in collagen-like peptides, providing attachment sites for carbohydrates in collagen and thus are critical for intermolecular crosslink stability, cause lysyl hydroxylase 3 deficiency.
*Procollagen-lysine—2-oxoglutarate 5-dioxygenase 3
Synonyms Bone fragility—arterial rupture—and deafness, LH3 deficiency