Prenatal diagnosis of vitamin D-dependent rickets, type II: response to 1,25-dihydroxyvitamin D in amniotic fluid cells and fetal tissues
| Autor: | Lea Even, Yosef Weisman, Zeev Hochberg, Alvin M. Kaye, Gideon Yedwab, Samuel Edelstein, Zvi Spirer, Cyril Legum, Niva Jaccard |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Vitamin
Adult medicine.medical_specialty Receptors Steroid Amniotic fluid Endocrinology Diabetes and Metabolism Clinical Biochemistry Rickets Kidney Biochemistry Mixed Function Oxygenases chemistry.chemical_compound Endocrinology Calcitriol Pregnancy Internal medicine Prenatal Diagnosis medicine Humans Receptor Cells Cultured Hypophosphatemia Familial Skin Fetus medicine.diagnostic_test business.industry Biochemistry (medical) Fibroblasts medicine.disease Amniotic Fluid Fetal Diseases chemistry In utero Enzyme Induction Pregnancy Trimester Second Amniocentesis Receptors Calcitriol Female Cholecalciferol business |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 71(4) |
| ISSN: | 0021-972X |
| Popis: | Vitamin D-dependent rickets type II (VDDR-II; hereditary resistance to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]), an autosomal recessive genetic disease that results from a failure to respond to 1,25-(OH)2D3, is characterized by severe rickets, hypocalcemia, growth retardation, and high prevalence of alopecia. We used amniotic fluid cells in the 17th week of gestation to detect VDDR-II in fetuses at risk for the defect. First, we demonstrated in cells obtained from 15 control pregnancies the presence of a specific high affinity 1,25-(OH)2D3 receptor (Kd = 0.3 x 10(-11) mol/L; maximal number of binding sites, 6.1 fmol/mg protein) and 1,25-(OH)2D3-induced 25-hydroxyvitamin D3-24-hydroxylase activity (up to 30-fold increase). Amniotic fluid cells from a woman who had already given birth to a child with VDDR-II contained receptors that bound [3H]1,25-(OH)2D3 normally and responded to 1,25-(OH)2D3 stimulation with a 10-fold increase in 24-hydroxylase activity. The fetus was, therefore, judged unaffected, and a normal baby girl was born. At the age of 16 months she did not demonstrate clinical or biochemical features of VDDR-II. Amniotic fluid cells from another mother of a child with VDDR-II were unable to bind [3H]1,25-(OH)2D3, and the hormone failed to stimulate 24-hydroxylase activity. VDDR-II in this fetus was confirmed after termination of pregnancy by the total inability of 1,25-(OH)2D3 to stimulate 24-hydroxylase activity in tissue explants and cell cultures prepared from the fetus's kidney and skin. In contrast, tissues from dead control fetuses responded to stimulation by 1,25-(OH)2D3 with a 3- to 10-fold increase in 24-hydroxylase activity. Fetal kidney and skin explants and cell cultures also synthesized a [3H]1,25-(OH)2D3-like metabolite from [3H]25-OHD3 as early as the 17th week of gestation. 1,25-(OH)2D3 (10 nM) decreased the in vitro synthesis of the [3H]1,25-(OH)2D3-like metabolite in tissues from dead control fetuses, but not from the affected fetus. Thus, human fetuses at midgestation already have the regulatory mechanisms responsive to 1,25-(OH)2D3 present postnatally. The prenatal diagnosis of VDDR-II is now possible and is indicated in a high risk family. |
| Databáze: | OpenAIRE |
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