RESUMO
We reviewed the clinical findings in 10 patients with lysyl hydroxylase deficiency (Ehlers-Danlos syndrome type VI) and report here the range of clinical severity in these patients. The distinctive feature common to all patients was muscle hypotonia with joint laxity in the newborn period, and moderate to severe kyphoscoliosis either was present or developed in almost all patients. Most patients also had some degree of skin abnormality observed in other types of Ehlers-Danlos syndrome: bruisability, abnormal scarring, and soft, distensible skin. These patients also are at risk for potentially catastrophic arterial rupture.
Assuntos
Colágeno/metabolismo , Síndrome de Ehlers-Danlos/enzimologia , Oxigenases de Função Mista/deficiência , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/deficiência , Estatura , Doenças Cardiovasculares/epidemiologia , Células Cultivadas , Síndrome de Ehlers-Danlos/fisiopatologia , Oftalmopatias/epidemiologia , Fibroblastos/enzimologia , Humanos , Recém-Nascido , Fenótipo , Pele/patologiaRESUMO
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.