A Genetic Study of Familial Hypophosphatemia and Vitamin D Resistant Rickets With a Review of the Literature

Winters, Robert W.; Graham, John B.; Williams, Trudy; McFalls, Vernon W.; Burnett, Charles H.

doi:10.1097/00005792-195805000-00001

Cited by 272 publications

(68 citation statements)

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“…A similar ratio has also been reported by others [7,33]. The significance of this finding is not clear; there is, of course, at least one X-linked gene which is responsible for renal tubular conservation of phosphorus [49], but how this predisposes to the manifestation ofvitamin D deficiency in males is unknown.…”

Section: Discussionsupporting

confidence: 85%

Hyperparathyroidism as the Cause of Hyperaminoaciduia and Phosphaturia in Human Vitamin D Deficiency

1967

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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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Section: Discussionsupporting

confidence: 85%

Hyperparathyroidism as the Cause of Hyperaminoaciduia and Phosphaturia in Human Vitamin D Deficiency

1967

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“…[13][14][15][16][17][18] There are marked variations in disease severity, both between and within families. However, it is not fully understood whether genotype can play a role in severity of phenotype.…”

Section: Introductionmentioning

confidence: 99%

Non-random distribution of mutations in the PHEX gene, and under-detected missense mutations at non-conserved residues

et al. 1999

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Thirty newly detected mutations in the PHEX gene are reported, and pooled with all the previously published mutations. The spectrum of mutations displayed 16% deletions, 8% insertions, 34% missense, 27% nonsense, and 15% splice site mutations, with two peaks in exon 15, and 17. Since 32.8% of PHEX amino acids were conserved in the endopeptidases family, the number of missense mutations detected at non-conserved residues was smaller than expected, whereas the number of nonsense mutations observed at non-conserved residues was very close to the expected number. Compared with conserved amino acids, the changes in nonconserved amino acids may result in benign polymorphisms or possibly mild disease that may go undiagnosed.

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“…Clinical involvement ranges from minor and unimportant hypophos- phatemia to florid rickets with stunted growth or osteomalacia (Winters et al 1958, Burnett et al 1964, Stickler et al 1970. As an X-linked dominant disorder, the disease tends to be more common in women but more severe in the male.…”

Section: Discussionmentioning

confidence: 99%

Enthesopathy as the presenting feature of X-linked hypophosphatemia: A case report

Chalmers

1993

Acta Orthopaedica Scandinavica

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A Genetic Study of Familial Hypophosphatemia and Vitamin D Resistant Rickets With a Review of the Literature

Cited by 272 publications

References 0 publications

Hyperparathyroidism as the Cause of Hyperaminoaciduia and Phosphaturia in Human Vitamin D Deficiency

Hyperparathyroidism as the Cause of Hyperaminoaciduia and Phosphaturia in Human Vitamin D Deficiency

Non-random distribution of mutations in the PHEX gene, and under-detected missense mutations at non-conserved residues

Enthesopathy as the presenting feature of X-linked hypophosphatemia: A case report

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