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

Fraser, Donald R.; Kooh, Sang Whay; Scriver, Charles R.

doi:10.1203/00006450-196711000-00001

Cited by 145 publications

(59 citation statements)

References 13 publications

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“…During the course of treatment with la-OH-D,, hypeiaminoaciduria subsided, in keeping with repair of the hypocalcemia and suppression of endogenous hyperparathyroidism (1,13,16,37). (Figs.…”

Section: Bone Responsementioning

confidence: 99%

“…Serum total alkaline phosphatase activity in patients I and 2 was determined by a modification of the ,method of Bessey et al (16); the King-Armstrong method (25) was used for patient 3. Urine amino acids were determined by, partition chromatography in two dimensions by the method of Dent (10) and measured semiquantitatively as described previously (13,16). Serum 25-hydroxyvitamin D was measured by the competitive.protein-binding assay of Haddad and Chyu (17).…”

Section: Protocols For Assessment Of 10-oh-d Efficacy(41)mentioning

confidence: 99%

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Response to Crystalline 1α-Hydroxyvitamin D3 in Vitamin D Dependency

Glorieux

et al. 1975

Pediatr Res

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ExtractThe therapeutic response to chemically_synthesized la-hydroxycholecalciferol (la-OH-D,) was studied in three patients with autosomal recessive vitamin D dependency (ARVDD). The daily maintenance dose for vitamin D,, to prevent signs of vitamin D deficiency in these patients, was 40-54.5 fig/kg, or about 100 times normal (Table 1). Withdrawal of maintenance therapy with vitamin D, resulted in the ultimate reappearance of the vitamin D depletion syndrome in patients I and 2 ( Figs. 1 and 2). The third patient presented with the deficiency syndrome despite adequate vitamin D nutrition and was recognized to have ARVDD.Treatment with la-OH-D, by mouth in all three patients at dose levels of 1-3 pg/24 hr (8@100 ng/kg) corrected hypocalcemia and suppressed parathyroid hormone-dependent renal loss of amino acids (Figs. 1,2, and 4). Rickets healed in 7-9 weeks on la-OH-D, alone (Fig. 3 ) The therapeutic response was rapid. It was usually seen first in the rise of serum calcium (Figs. 5 and 6). Withdrawal of la-OH-D, was followed first by a fall of serum phosphorus, then by a fall in serum calcium; the latter occurred within about 2 weeks of withdrawal.Because the synthesis of la-OH-D, is simpler than for la,25-dihydroxycholecalciferol and because the former is an effective therapeutic analog of vitamin D hormone, we believe these studies in ARVDD reveal la-OH-D, to be the agent of choice for treatment of this and analogous diseases. SpeculationVitamin D dependency or pseudodeficiency rickets is believed to be an inborn error of vitamin D hormone biosynthesis. The putative abnormal enzyme is 25-hydroxycholecalciferol 1-hydroxylase in the recessively inherited trait. Consequently, this experiment of nature offers a special opportunity to examine the requirement in human subjects, for la-hydroxyvitamin D, metabolites.Patients with ARVDD (14, 18, 36) develop signs of severe postnatal vitamin D deficiency, despite a nutritional intake of vitamin D, or vitamin D, (40) that would prevent rickets in normal subjects; hence the term pseudodeficiency preferred by some investigators (34). Persistent hypocalcemia appearing soon after birth is accompanied by an excess of circulating parathyroid hormone (I) which in turn is associated with hyperphosphaturia and hyperaminoaciduria (1, 37). Elevated serum alkaline phosphatase activity, severe rachitic bone lesions, and enamel hypoplasia affecting teeth that form postnatally complete the clinical syndrome ( I , l I, 14, 18, 34, 36). Maintenance treatment with vitamin D, only at levels about 100 times the normal requirement fully reverses the manifestations of deficiency hence the term vitamin D dependency (18,36).The origin of the disturbed physiology in ARVDD lies in a selective disturbance of calcium absorption by intestine (18). A defect either in the biosynthesis of the active hormone form of vitamin D or in the ability of target organ(s) to respond to vitamin D hormone has been proposed (36) to explain the dependency on vitamin D,, D,, or 25-OH-D, of patients with ARVDD. ARVDD...

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Section: Bone Responsementioning

confidence: 99%

Section: Protocols For Assessment Of 10-oh-d Efficacy(41)mentioning

confidence: 99%

Response to Crystalline 1α-Hydroxyvitamin D3 in Vitamin D Dependency

Glorieux

et al. 1975

Pediatr Res

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“…Though the rise in serum PTH is a well-characterized bio-adaptive response in VDD (Fraser et al, 1967), a majority of volunteers with chronic VDD have normal PTH values (Goswami et al, 2000). Vitamin D and its metabolites act through vitamin D receptor (VDR) and the latter promotes transcription of calbindin-9k and calcium transporter TVRP6 genes (Ramasamy, 2006).…”

Section: Introductionmentioning

confidence: 99%

Presence of 25(OH)D deficiency and its effect on vitamin D receptor mRNA expression

et al. 2008

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Background and objectives: Vitamin D and its metabolites act through vitamin D receptor (VDR). We hypothesized that subjects with low serum 25(OH)D levels but normal PTH might have increased VDR expression. Design and Methods: VDRmRNA expression was assessed by real time PCR in duodenal mucosa and PBMC (peripheral blood mononuclear cells) in 45 subjects with normal duodenoscopy and in PBMC alone in 48 healthy volunteers with hypovitaminosis D. 25(OH)D, PTH and VDRmRNA expression in PBMC was reassessed after 8 weeks of oral cholecalciferol (60 000 IU per week) in a subset (n ¼ 23) of healthy volunteers. Results and Conclusions: The VDRmRNA expressions in the duodenum and PBMC were significantly correlated (r ¼ 0.42), but the expression was 13 times higher in the former than the latter. The mean VDRmRNA expression was similar in 25(OH)Ddeficient subjects with or without PTH elevation, both in the duodenum and PBMC. The PBMC VDRmRNA expression showed no significant change after cholecalciferol supplementation. A weak correlation coefficient between duodenal mucosa and PBMC VDRmRNA suggests that caution needs to be exercised while using the latter as a surrogate for other sites.

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“…La hipocalcemia estimula la parathormona y el hiperparatiroidismo secundario puede provocar alteracion funcional del tubulo proximal del rinon, con aminoaciduria, acidosis tubular proximal, fosfaturia y glicosuria, o, dicho en otros terminos el hiperparatiroidismo secundario puede provocar un sindrome de Fanconi (10). No se ha aclarado por que, en algunos de estos casos, la alteracion funcional del tubulo no compromete la reabsorci6n de glucosa y no hay glicosuria (11).…”

Section: Comentariounclassified