1. A child is described who presented with very severe rickets and gross myopathy. The clinical, biochemical and radiological signs were identical with those to be expected of a very chronic and severe vitamin D deficiency. The child's diet, however, had been normal. 2. All the pathological signs, except for residual dwarfism and leg bowing, disappeared on treatment with very large doses of vitamin D2. Ordinary anti-rachitic doses had no effect. 3. We suggest that this child demonstrates a true resistance to the action of vitamin D and that the defect is permanent. The findings in two similar patients that we have seen suggest that the condition is inherited as an autosomal recessive gene, and that it may be the same disease as that described in the continental literature as "hereditäre pseudo-mangelrachitis" and by other names. 4. The disease seems distinct clinically and biochemically from the disease originally described under the name "vitamin resistant rickets," which does not respond so well to massive vitamin D therapy and which is usually inherited as a sex-linked dominant gene.
1. A clinical, radiological and histological description of a patient with fibrogenesis imperfecta ossium is given. We think that this is the first case in which diagnosis has been made during the life of the patient. 2. The disease is characterised by a defect in the formation of the collagen fibres of the bone matrix. There is also a failure of normal calcification of the matrix, giving rise to the appearance of wide "osteoid" seams. When examined with the polarising microscope and when stained with Gomori's reticulin stain the collagen fibres can be seen to be grossly deficient and abnormal. 3. The patient presented at the age of fifty-four years with bone pain and multiple fractures. The only biochemical abnormality detected in the plasma was an elevated alkaline phosphatase. He was also in negative calcium balance. 4. Treatment with vitamin D2, later changed to dihydrotachysterol, appears to have produced clinical, biochemical and radiological improvement. It appears that a direct action of the vitamin on the abnormal bone collagen must be postulated, in addition to its known actions on the calcifying mechanisms. 5. An unusual feature of the case was the slow development of a total unresponsiveness to large doses of vitamin D2, in spite of a markedly elevated level of vitamin D in the plasma. There was later a response to a much smaller dose of dihydrotachysterol, which is being maintained to date.
1. We have described here various forms of rickets and osteomalacia that we have studied ourselves and have come to recognise as comprising definite syndromes. We have included only diseases in which hereditary factors have been proved or might be suspected to play a part. 2. There are more of these syndromes than previously defined. 3. All these hereditary diseases can be treated, usually very satisfactorily, using the same general principles and with only very few simple medicines such as vitamin D and sodium bicarbonate. Careful control and long follow-up, however, may be required to achieve best results and to avoid accidents. 4. A study of the genetics of the diseases is a help in diagnosis and treatment. Broadly speaking the group of diseases which mimic vitamin D deficiency more or less closely tend to be inherited in dominant fashion. The groups with more severe degree of renal-tubule abnormality are inherited as recessives. 5. When more than one member of a family is affected it has been found that in each family each syndrome runs true to type.
1. Cases of rickets and osteomalacia caused by kidney tubule defects have been classified into six sub-groups according to the various disturbances of tubule function concerned. 2. The manifestations, treatment and prognosis appropriate to the sub-groups have been considered. 3. The name "tubular rickets" (or osteomalacia) is suggested for these cases of mainly tubule dysfunction in contrast to "glomerular rickets" (or osteomalacia) which might be used to distinguish cases in which defect in the glomeruli overshadows and precedes that in the tubules.
