Mild Idiopathic Infantile Hypercalcemia – Part 2: A Longitudinal Observational Study

2021 ◽  
Author(s):  
Nina Lenherr-Taube ◽  
Michelle Furman ◽  
Esther Assor ◽  
Yesmino Elia ◽  
Carol Collins ◽  
...  
Keyword(s):  
Vitamin D ◽  
Dietary Assessment ◽  
Dietary Calcium ◽  
Urinary Calcium ◽  
Renal Ultrasound ◽  
Vitamin D Metabolism ◽  
Low Calcium Diet ◽  
Observational Cohort ◽  
Idiopathic Infantile Hypercalcemia ◽  
Serum Pth

Abstract Context Idiopathic Infantile Hypercalcemia (IIH) is an uncommon disorder with variable clinical features. The natural history and response to dietary calcium and vitamin D restriction in IIH remains unclear. Objective The aim of this study is to describe the clinical and biochemical response to dietary calcium and vitamin D restriction in a genetically characterized cohort of mild IIH. Methods This is a longitudinal, observational cohort study of 20 children with mild IIH monitored for a median of 21months. Biochemical measures, dietary assessment and yearly renal ultrasound results, since the time of diagnosis, were obtained and assessed prospectively every 4-6 months. Results Median age at initial diagnosis was 4·5 months. Median levels of serum calcium (2·82 mmol/l) and 1,25 (OH)2 D (192 pmol/l) were elevated whereas serum PTH was reduced (10 ng/l). Urinary calcium:creatinine ratio was elevated for some, but not all individuals (median 1·49 mmol/mmol). All patients who were managed with a low calcium diet showed an improvement in serum and urinary calcium measures, but the serum concentration of 1,25(OH)2D and 1,25(OH)2D/PTH ratio remained elevated. In 2 of the 11 subjects, renal calcification worsened. There were no differences in response between individuals with CYP24A1 or SLC34A1/A3 variants. Conclusion The clinical presentation of mild IIH is variable and dietary calcium and vitamin D restriction does not consistently normalize elevated 1,25(OH)2D concentrations or prevent worsening of renal calcification in all cases. Therapeutic options should target the defect in vitamin D metabolism.

scholarly journals Craniotabes in Normal Newborns: The Earliest Sign of Subclinical Vitamin D Deficiency

2008 ◽  
Vol 93 (5) ◽  
pp. 1784-1788 ◽  
Author(s):  
Junko Yorifuji ◽  
Tohru Yorifuji ◽  
Kenji Tachibana ◽  
Shizuyo Nagai ◽  
Masahiko Kawai ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Urinary Calcium ◽  
University Hospital ◽  
X Rays ◽  
Intact Pth ◽  
Calcium Phosphorus ◽  
Serum Pth ◽  
Normal Neonates ◽  
Breast Fed

Abstract Context: Craniotabes in otherwise normal neonates has been regarded as physiological and left untreated. Objective: Our objective was to investigate the role of vitamin D deficiency in the development of craniotabes in normal neonates. Design and Setting: Newborn screening of craniotabes was conducted at the single largest obstetrical facility in Kyoto, Japan. Follow-up study at 1 month was conducted at Kyoto University Hospital. Subjects: A total of 1120 consecutive normal Japanese neonates born in May, 2006, through April, 2007, were included in the study. Main Outcome Measures: The incidence of craniotabes was scored each month. Neonates with craniotabes were followed up at 1 month with measurements of serum calcium, phosphorus, alkaline phosphatase (ALP), intact PTH, 25-OH vitamin D (25-OHD), urinary calcium, phosphorus, creatinine, and hand x-rays. Results: Craniotabes was present in 246 (22.0%) neonates, and the incidence had obvious seasonal variations, highest in April-May and lowest in November. At 1 month, infants with craniotabes had significantly higher serum ALP compared with normal neonates; 6.9% of them had elevated intact PTH over 60 pg/ml, and 37.3% had 25-OHD less than 10 ng/ml. When separately analyzed according to the method of feeding, 56.9% of breast-fed infants showed 25-OHD less than 10 ng/ml, whereas none of formula/mixed-fed infants did, and breast-fed infants had significantly higher serum PTH and ALP compared with formula/mixed-fed infants. Summary: These results suggest that craniotabes in normal neonates is associated with vitamin D deficiency in utero, and the deficiency persists at 1 month in many of them, especially when breast-fed.

PTH regulates expression of ClC-5 chloride channel in the kidney

2000 ◽  
Vol 278 (2) ◽  
pp. F238-F245 ◽  
Author(s):  
Ian V. Silva ◽  
Carol J. Blaisdell ◽  
Sandra E. Guggino ◽  
William B. Guggino
Keyword(s):  
Vitamin D ◽  
Protein Expression ◽  
Chloride Channel ◽  
Urinary Calcium ◽  
Kidney Cortex ◽  
Lower Serum ◽  
Protein Levels ◽  
Calcium Reabsorption ◽  
Mrna And Protein Expression ◽  
Serum Pth

Mutations in the chloride channel, ClC-5, have been described in several inherited diseases that result in the formation of kidney stones. To determine whether ClC-5 is also involved in calcium homeostasis, we investigated whether ClC-5 mRNA and protein expression are modulated in rats deficient in 1α,25(OH)2 vitamin D3 with and without thyroparathyroidectomy. Parathyroid hormone (PTH) was replaced in some animals. Vitamin D-deficient, thyroparathyrodectomized rats had lower serum and higher urinary calcium concentrations compared with control animals as well as lower serum PTH and calcitonin concentrations. ClC-5 mRNA and protein levels in the cortex decrease in vitamin D-deficient, thyroparathyroidectomized rats compared with both control and vitamin D-deficient animals. ClC-5 mRNA and protein expression increase near to control levels in vitamin D-deficient, thyroparathyroidectomized rats injected with PTH. No significant changes in ClC-5 mRNA and protein expression in the medulla were detected in any experimental group. Our results suggest that PTH modulates the expression of ClC-5 in the kidney cortex and that neither 1α,25(OH)2 vitamin D3 nor PTH regulates ClC-5 expression in the medulla. The pattern of expression of ClC-5 varies with urinary calcium. Animals with higher urinary calcium concentrations have lower levels of ClC-5 mRNA and protein expression, suggesting that the ClC-5 chloride channel plays a role in calcium reabsorption.

Contrasting effects of intravenous and oral etidronate on vitamin D metabolism in man

1988 ◽  
Vol 74 (1) ◽  
pp. 101-106 ◽  
Author(s):  
P. J. Lawson-Matthew ◽  
D. F. Guilland-Cumming ◽  
A. J. P. Yates ◽  
R. G. G. Russell ◽  
J. A. Kanis
Keyword(s):  
Vitamin D ◽  
Urinary Excretion ◽  
Progressive Increase ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Renal Tubular Reabsorption ◽  
Early Effects ◽  
Renal Tubular

1. We have studied the early effects of intravenously and orally administered etidronate on vitamin D metabolism and indirect indices of calcium and skeletal metabolism in 17 patients with Paget's disease of bone. 2. Administration of etidronate by mouth (700–1400 mg daily for 1 month) or its intravenous infusion (300 mg daily for 5 days) decreased bone resorption as judged by urinary excretion of hydroxyproline and significantly increased renal tubular reabsorption of phosphate. No significant change in serum activity of alkaline phosphatase was noted with either regimen. 3. When etidronate was given by mouth there was a progressive decrease in fasting urinary calcium excretion and a rise in serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. In contrast, intravenous etidronate decreased serum values of l,25-(OH)2D3 and was associated with a progressive increase in fasting calcium excretion, suggesting a decrease in the net influx of calcium from the extracellular compartment to bone. Significant inverse correlations were noted between the change induced in 1,25-(OH)2D3 values at 2 weeks and the changes in serum calcium, phosphate and fasting urinary excretion of calcium. 4. These observations suggest that the different effects of intravenous and oral etidronate on l,25-(OH)2D3 values are a consequence of different doses of etidronate used and the different effects of these regimens on the accretion of calcium into bone.

Effects of Dietary Calcium and Phosphorus on Vitamin D Metabolism and Calcium Absorption in Hamster

1996 ◽  
Vol 211 (3) ◽  
pp. 281-286 ◽  
Author(s):  
H. P. Schedl ◽  
T. Conway ◽  
R. L. Horst ◽  
D. L. Miller ◽  
C. K. Brown
Keyword(s):  
Vitamin D ◽  
Calcium Absorption ◽  
Dietary Calcium ◽  
Vitamin D Metabolism ◽  
Calcium And Phosphorus

scholarly journals IDIOPATHIC INFANTILE HYPERCALCEMIA . DESCRIPTION OF CLINICAL CASES AND REVIEW.

2017 ◽  
Vol 63 (1) ◽  
pp. 51-57
Author(s):  
Yulia V. Tikhonovich ◽  
Anna A. Kolodkina ◽  
Kristina S. Kulikova ◽  
Yulia Yu. Golubkina ◽  
Natalia Yu. Kalinchenko ◽  
...  
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Family Counseling ◽  
Compound Heterozygous ◽  
Loss Of Function ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Low Calcium Diet ◽  
Idiopathic Infantile Hypercalcemia ◽  
Vitamin D Supplements

Vitamin D plays a central role in calcium homeostasis. Impaired degradation  of 1,25-dihydroxyvitamin D due to loss-of-function mutations in CYP24A1 leads to significant hypercalcemia, hypercalciuria,  suppressed level of parathyroid hormone (PTH),  nephrocalcinosis and nephrolithiasis.  This condition has been called Idiopathic infantile hypercalcemia. Treatment includes low calcium diet, rehydration, furosemid,  avoidance of vitamin D supplements  and sun protection.   In severe  cases   glucocorticoids, ketoconazole,  bisphosphonates  and  hemodiafiltration may be used. Early diagnosis of the disease allows to develop an individual plan for managing these patients to prevent the formation of kidney disease, to conduct a genetic family counseling. Here, we describe the cohort of  patients (3  children, 2 adults)  with significant hypercalcemia due to  homo- and compound heterozygous mutations in CYP24A1, describe  the main clinical and laboratory characteristics, diagnosis, principles and foundations of the management of patients with this pathology.

scholarly journals Evaluation of Ergocalciferol or Cholecalciferol Dosing, 1,600 IU Daily or 50,000 IU Monthly in Older Adults

2011 ◽  
Vol 96 (4) ◽  
pp. 981-988 ◽  
Author(s):  
N. Binkley ◽  
D. Gemar ◽  
J. Engelke ◽  
R. Gangnon ◽  
R. Ramamurthy ◽  
...  
Keyword(s):  
Vitamin D ◽  
Alkaline Phosphatase ◽  
Serum Calcium ◽  
Urinary Calcium ◽  
Community Dwelling ◽  
Individual Response ◽  
Specific Alkaline Phosphatase ◽  
Bone Specific Alkaline Phosphatase ◽  
Hydroxyvitamin D ◽  
Serum Pth

Abstract Context: Whether ergocalciferol (D2) and cholecalciferol (D3) are equally effective to increase and maintain serum 25-hydroxyvitamin D [25(OH)D] concentration is controversial. Objective: The aim of the study was to evaluate the effect of daily and once monthly dosing of D2 or D3 on circulating 25(OH)D and serum and urinary calcium. Design, Setting and Participants: In a university clinical research setting, 64 community dwelling adults age 65+ were randomly assigned to receive daily (1,600 IU) or once-monthly (50,000 IU) D2 or D3 for 1 yr. Main Outcome Measures: Serum 25(OH)D, serum calcium, and 24-h urinary calcium were measured at months 0, 1, 2, 3, 6, 9, and 12. Serum PTH, bone-specific alkaline phosphatase, and N-telopeptide were measured at months 0, 3, 6, and 12. Results: Serum 25(OH)D was less than 30 ng/ml in 40% of subjects at baseline; after 12 months of vitamin D dosing, levels in 19% of subjects (n = 12, seven receiving daily doses and five monthly doses) remained low, despite compliance of more than 91%. D2 dosing increased 25(OH)D2 but produced a decline (P < 0.0001) in 25(OH)D3. Substantial between-individual variation in 25(OH)D response was observed for both D2 and D3. The highest 25(OH)D observed was 72.5 ng/ml. Vitamin D administration did not alter serum calcium, PTH, bone-specific alkaline phosphatase, N-telopeptide, or 24-h urine calcium. Conclusions: Overall, D3 is slightly, but significantly, more effective than D2 to increase serum 25(OH)D. One year of D2 or D3 dosing (1,600 IU daily or 50,000 IU monthly) does not produce toxicity, and 25(OH)D levels of less than 30 ng/ml persist in approximately 20% of individuals. Substantial between-individual response to administered vitamin D2 or D3 is observed.

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