title: Inherited human collagen lysyl hydroxylase deficiency: ascorbic acid response.
abstract: A patient is described with congenital hypotonia, lax joints, friable skin, hemorrhagic scars, high-arched palate, and borderline microcornea. Acid hydrolyzed whole skin collagen had a reduced hydroxylysine content of 0.5 residues per 1,000 as compared to 5.1 +/- 0.7 in control skin. Collagen lysyl hydroxylase in dialyzed subcellular fractions of cultured skin fibroblasts required L-ascorbate as a principal cofactor. Activity of this enzyme in cultured skin fibroblasts derived from this patient, his father, and mother were 17%, 66%, and 39% of control values, respectively. Collagen prolyl hydroxylase activity was normal. Pharmacologic amounts of oral vitamin C (4 gm/day) produced an increase and withdrawal resulted in abrupt diminution of urinary excretion of hydroxylysine. Over a two-year period the patient's wound healing and muscle strength improved and corneal diameter increased. Hydroxylysine content of the skin did not increase.
mesh_terms: D001205:Ascorbic Acid / Q000627:therapeutic use*; D002648:Child; D004796:Clinical Enzyme Tests; D004535:Ehlers-Danlos Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006901:Hydroxylysine / Q000378:metabolism / Q000652:urine; D008297:Male; D006899:Mixed Function Oxygenases / Q000172:deficiency*; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase / Q000172:deficiency*; D012867:Skin / Q000201:enzymology
chemical_list: D006901:Hydroxylysine; D006899:Mixed Function Oxygenases; D008240:Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase; D001205:Ascorbic Acid