The expression of constitutively active PTH-PTHrp receptors in kidney, bone, and growth-plate chondrocytes provides a plausible genetic explanation for mineral-ion abnormalities and metaphyseal changes in patients with Jansen's disease.

X-Linked hypophosphatemic rickets (XLH) is characterized by hypophosphatemia, rickets, and impaired growth. Despite oral phosphate and 1,25-dihydroxyvitamin D(3) treatment, many patients have suboptimal growth and bone healing. The aim of this study was to assess whether age at treatment onset impacts the outcome. Growth data, biochemistry, and radiographs of 19 well-controlled patients with XLH were analyzed retrospectively. Patients were divided into two groups based on the age at treatment onset (group 1, <1.0 yr; group 2, >or=1.0 yr). The median height z-score was higher in group 1 (n = 8) than in group 2 (n = 11) at treatment onset [-0.4 SD score (SDS) vs. -1.7 SDS; P = 0.001], at the end of the first treatment year (-0.7 SDS vs. -1.8 SDS; P = 0.009), throughout childhood (P > 0.05) and until predicted adult height (-0.2 SDS vs. -1.2 SDS; P = 0.06). The degree of hypophosphatemia was similar in both groups, but serum alkaline phosphatase remained higher in group 2 throughout childhood. Radiographic signs of rickets were more marked in group 2, but even patients with early treatment developed significant skeletal changes of rickets. These data suggest that treatment commenced in early infancy results in improved outcome in patients with XLH, but does not completely normalize skeletal development.

We retrospectively reviewed the presentation and management of children with primary hyperparathyroidism (PHPT) from 1973 to 1995 at a paediatric tertiary-care centre. There were 11 patients (6 females), aged 12.3-17.7 years at presentation, with sporadic PHPT confirmed by histopathology (single adenoma). Presentation consisted of renal colic, or non-specific gastrointestinal, musculoskeletal or neurological symptoms. Misdiagnosis was common until hypercalcaemia was identified, 0.5-24 months after onset of symptoms (mean 7.7 months). All patients had hypercalcaemia and low-normal serum phosphate. The parathyroid hormone (PTH) radioimmunoassay used before 1986 was elevated in 1/4 patients; the intact PTH assay used after 1986 was elevated in 7/7 patients. At presentation, six had end-organ damage: band keratopathy, renal lesions, and/or bone disease. Preoperative localization was accurate in 0/4 patients diagnosed before 1986, but 5/7 patients diagnosed after 1986: three by ultrasound or sestamibi scan alone, and two by ultrasound and technetium scan. Surgical outcome was not dependent upon the accuracy of pre-operative localization. PHPT is rare in children but usually associated with end-organ damage, presumably due to delayed diagnosis. It should be considered in the differential diagnosis of unexplained non-specific complaints. The intact PTH assay greatly assists pre-operative diagnosis. The usefulness of pre-operative localization requires further research.

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ExtractThirty-nine infants with simple vitamin D deficiency were studied; three stages of deficiency were recognized. Stage I comprised hypocalcemia, usually as the sole important biochemical finding, while convulsions were a common clinical sign. Stage I1 revealed normocalcemia with hyperaminoaciduria, hypophosphatemia, and hyperphosphaturia; rickets was also in evidence. Stage I11 was comparable to stage 11, but with recurrence of hypocalcemia and convulsions, the rickets was more severe. Patients progressed spontaneously from the early to the later stages of the deficiency syndrome; administration of parathyroid extract appeared to accelerate the rate of progression. Calcium infusion and vitamin D therapy each initially raised the serum calcium level in hypocalcemic patients; thereafter, aminoaciduria and hyperphosphaturia were suppressed.These diverse observations were interpreted in accordance with current knowledge of vitamin D and parathyroid hormone interrelations. The acquired excretory abnormality involving amino acid and phosphorus is the result of impaired tubular absorption; this defect is considered to be dependent on the development of endogenous reactive hyperparathyroidism, and not dependent on cellular deficiency of vitamin Dper se. The stimulus for the hyperparathyroidism is hypocalcemia induced by deficiency of vitamin D. Normocalcemia is restored if sufficient vitamin D is present in cellular membranes to amplify the stimulative action of parathyroid hormone on intestinal transport of calcium and its release from bone. Severe deficiency of vitamin D blocks this regulatory effect upon calcium, but does not block the inhibitory effect of parathyroid hormone on renal tubular transport of amino acids and phosphorus. SpeculationAn excess of parathyroid hormone rather than a simple deficiency of vitamin D at the renal tubular epithelial cell appears to cause the disturbance of transport affecting the absorption phosphorus, amino acids and other solutes. This impairment of function is the price paid in renal cellular economy for the conservation of calcium. The cellular mechanisms underlying this coexistent inhibitory effect of parathyroid hormone constitutes an important and fascinating subject for further investigation.

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Prolonged very high dose oral Pi treatment is a major risk factor for the development of tertiary hyperparathyroidism in X-linked hypophosphatemic rickets.