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Biochemical parameters of Ca homeostasis in fetal and maternal plasma and placental transfer of Ca, Pi and vitamin D metabolites were measured during pregnancy and at parturition. Control pigs and pigs with inherited pseudo-vitamin D-deficiency rickets, type I (PVDR), which are devoid of renal calcitriol production, were used. Although sows with PVDR normally require treatment with massive doses of vitamin D at intervals of 4 weeks to stabilize Ca and Pi concentrations in plasma, these plasma parameters tended to normalize during the first 3 months of pregnancy when the vitamin D treatment was discontinued about 4 weeks before conception. In homozygote sows plasma calcitriol concentrations remained unphysiologically low and the 25OHD3 concentrations increased steadily during pregnancy reaching higher levels than those found in control sows. Despite hypocalcaemia and hypophosphataemia of the homozygote sows at term, fetal Ca and Pi concentrations were normal. This demonstrated a higher feto-maternal concentration gradient in PVDR pigs than in control pigs. It is concluded that maintenance of Ca and Pi homeostasis of the feto-maternal system, including active transplacental transport in pigs, is at least partly independant from calcitriol.

We have observed congenital hypophosphataemic rickets in two sons of a marriage between first cousins, their mother being clinically and biochemically normal. Both patients are now approaching middle age. In addition to severe childhood rickets and lifelong hypophosphataemia, their disease is characterised by gross osteosclerosis with extraskeletal ossification, clinically persistent osteomalacia in one and spinal cord compression in the other. The genetics of this disease can be satisfactorily explained only on the basis of autosomal recessive inheritance, a mode which has only once before been reported in the literature. The severity of certain features, which would be expected in a homozygous state, may help our understanding of the more usual X-linked form.

Since structure and specifity of amino acid transport systems are basically similar in kidney and intestines it was suspected that rickets associated with hyperaminoaciduria was linked with defective intestinal amino acid uptake. Therefore amino acid absorption from everted sacs of small intestines was studied in 2 piglets suffering from vitamin D dependent rickets, and 7 healthy piglets using 14-C labelled amino acids. The experiments revealed an unaffected intestinal absorption in the rachitic animals, whereas the uptake decreased significantly with increasing age of the experimental animals. The results from these studies suggest that regulatory factors in the blood system, e.g. increased level of PTH or lack of specific vitamin D metabolites, do not directly affect amino acid transport systems in kidney and intestines. It is concluded that hyperaminoaciduria has to be mediated through specific and thus far unidentified effects at the tubular cell level.

The case of a 4.5-year-old girl with autosomal recessive vitamin D dependency is described. Although she had been effectively treated since one month postpartum with 1 alpha-hydroxycholecalciferol [1 alpha(OH)D3, alfacalcidol], her mean alkaline phosphatase (EC 3.1.3.1) activity in serum increased to 3680 U/L from a stable value [335 (SD 50) U/L; n = 12] within three weeks, then returned to baseline over the ensuing four months. Transient hyperphosphatasemia was diagnosed. Extensive investigation of an isolated episodic increase in alkaline phosphatase activity is as superfluous in the child with adequately treated metabolic bone disease as it is in other healthy and asymptomatic children.

A sex-linked dwarf strain of chickens fed a practical chick starter had a high incidence of rickets while other strains, including the Cornell K strain reared under the same conditions, had no evidence of this disease. In studies of the calcium, phosphorus and vitamin D requirements of the dwarf and K strains, no strain differences in requirement for phosphorus or vitamin D for maximal bone mineralization were apparent. The vitamin D requirement for growth was less for dwarfs than for the K strain; the reverse was observed for phosphorus. A marginal level of calcium (0.6%) did not depress growth or bone ash in either strain. Dwarfs had significantly lower bone ash than chicks of the K strain when dietary levels of calcium, available phosphorus and vitamin D were adequate (1.0%, 0.73% and 400 I.U./kg., respectively). When the diet contained a low level of one nutrient (0.6% calcium, 0.33% of phosphorus or 100 I.U./kg. vitamin D), neither strain was affected. Low levels of two nutrients significantly decreased bone ash in dwarfs but not in the K strain. Low levels of all three nutrients depressed bone ash in both strains, but most markedly in the dwarfs. These studies indicate that chicks of the Cornell dwarf strain have a low bone mineral content and are unusually susceptible to rickets.

Two siblings (boy and girl) born to a mother with familial hypophosphatemic rickets had abnormal values of serum phosphorus and serum alkaline phosphatase at the age of six weeks. At this age therapy with 1 alpha-hydroxycholecalciferol (1 alpha OHD3) and phosphate was started resulting in both siblings having normal growth of body length and radiological healing of the bone lesions but persistently low values of fasting serum phosphorus during the time of observation up to 60 and 26 months of age, respectively. Phosphate and 1 alpha OHD3 have a positive influence on serum phosphorus through their effect on the intestine. Neither of the patients developed hypercalcaemia during treatment. It seems, therefore, that the early administration of 1 alpha OHD3 with phosphate in infants with familial hypophosphatemic rickets prevents dwarfism and has a positive effect on intestinal absorption of phosphorus but not on fasting hypophosphatemia.

X-linked familial hypophosphatemic rickets (X.L.F.H.R.) is one of the D resistant rickets. The inheritance pattern is related to the X chromosome. Most constant feature is hypophosphatemia. Pathogenesis is still a subject of controversy. There are three main theories: a) An abnormal vitamin D metabolism. b) Secondary hyperparathyroidism developping as a result of the diminished calcium absorption by gut. c) A primary deffect of phosphate transport al various levels. Authors study and comment six cases of X.L.F.H.R., three of which belong to the same family. Clinical, radiological and higtological findings correspond to those of severe rickets. It is a chronic disease which affects children during growth period, giving rise to deforming bones invalidism. Treatment consists on continuous administration of oral phosphate and vitamin D.

Administration of large doses of vitamin D2 brought about a marked increase of 25-hydroxyvitamin D in both the patients with vitamin D dependency and hypophosphatemic vitamin D-resistant rickets. During the administration of vitamin D2, increment of 1,25-dihydroxyvitamin D was marked in hypophosphatemic vitamin D-resistant rickets, but far smaller in vitamin D dependency. In the latter, however, the 1,25-dihydroxyvitamin D reached the level close to the normal adult values. 1 alpha-hydroxyvitamin D3 was found 50 approximately 100 times as effective as vitamin D2 in 2 patients with vitamin D dependency (optimum maintenance dose: 0.05 micrograms/kg/day). It was concluded that 1 alpha-hydroxylation in the renal tubules is markedly defective in the patients with vitamin D dependency, but that a large dose of vitamin D2 is able to cause a definite increase in serum concentration of 1,25-dihydroxyvitamin D resulting in improvement of the rickets.