Mild Idiopathic Infantile Hypercalcemia – Part 1: Biochemical and Genetic Findings

2021 ◽  
Author(s):  
Nina Lenherr-Taube ◽  
Edwin J Young ◽  
Michelle Furman ◽  
Yesmino Elia ◽  
Esther Assor ◽  
...  
Keyword(s):  
Vitamin D ◽  
Dietary Assessment ◽  
Molecular Genetic ◽  
Elevated Serum ◽  
Molecular Genetic Analysis ◽  
Vitamin D Metabolites ◽  
Genetic Associations ◽  
Cross Sectional ◽  
Severe Hypercalcemia ◽  
Idiopathic Infantile Hypercalcemia

Abstract Context Idiopathic Infantile Hypercalcemia (IIH), an uncommon disorder characterized by elevated serum concentrations of 1,25(OH)2D and low PTH levels, may present with mild to severe hypercalcemia during the first months of life. Biallelic variants in the CYP24A1 or SLC34A1 genes are associated with severe IIH. Little is known about milder forms. Objective To characterize the genetic associations and biochemical profile of mild IIH. Methods This is a cross-sectional study including children between 6 months and 17 years of age with IIH who were followed in the Calcium Clinic at the Hospital for Sick Children (SickKids), Toronto, Canada. 20 children with mild IIH on calcium-restricted diets were evaluated. We performed a dietary assessment and analysed biochemical measures including vitamin D metabolites and performed a stepwise molecular genetic analysis. Complementary biochemical assessments and renal ultrasounds were offered to first-degree family members of positive probands. Results The median age was 16 months. Median serum levels of calcium (2·69 mmol/L), urinary Calcium:Creatinine ratio (0·72 mmol/mmol) and 1,25(OH)2D (209 pmol/L) were elevated while intact PTH was low normal (22·5 ng/L). Mean1,25(OH)2D/PTH and 1,25(OH)2D/25(OH)D ratios were increased by comparison to healthy controls. Eleven subjects (55%) had renal calcification. Genetic variants were common (65%) with the majority being heterozygous variants in SLC34A1 and SLC34A3 while a minority showed variants of CYP24A1 and other genes related to hypercalciuria. Conclusion The milder form of IIH has a distinctive vitamin D metabolite profile and is primarily associated with heterozygous SLC34A1 and SLC34A3 variants.

scholarly journals Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

2016 ◽  
Vol 37 (5) ◽  
pp. 521-547 ◽  
Author(s):  
Peter J. Tebben ◽  
Ravinder J. Singh ◽  
Rajiv Kumar
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Active Form ◽  
Elevated Serum ◽  
Diagnosis And Treatment ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Stone Formers ◽  
25 Hydroxyvitamin D

AbstractHypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.

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.

A Cross-Sectional Study on Biochemical Parameters of Bone Turnover and Vitamin D Metabolites in Healthy Dutch Children and Young Adults

2002 ◽  
Vol 57 (5-6) ◽  
pp. 170-179 ◽  
Author(s):  
Inge M. van der Sluis ◽  
Wim C. Hop ◽  
Johannes P.T.M. van Leeuwen ◽  
Huib A.P. Pols ◽  
Sabine M.P.F. de Muinck Keizer-Schrama
Keyword(s):  
Vitamin D ◽  
Young Adults ◽  
Bone Turnover ◽  
Biochemical Parameters ◽  
Cross Sectional Study ◽  
Vitamin D Metabolites ◽  
Sectional Study ◽  
Cross Sectional ◽  
Children And Young Adults ◽  
Dutch Children

scholarly journals FINDIET 2007 Survey: energy and nutrient intakes

2010 ◽  
Vol 13 (6A) ◽  
pp. 920-924 ◽  
Author(s):  
Pirjo Pietinen ◽  
Merja Paturi ◽  
Heli Reinivuo ◽  
Heli Tapanainen ◽  
Liisa M Valsta
Keyword(s):  
Vitamin D ◽  
Dietary Habits ◽  
Salt Intake ◽  
Picture Book ◽  
Dietary Assessment ◽  
Population Based ◽  
Nutrient Intakes ◽  
Finnish Population ◽  
Cross Sectional ◽  
Positive Direction

AbstractObjectiveThe National FINDIET surveys are carried out every 5 years to monitor dietary habits and nutrient intake of the adult Finnish population. The latest survey was carried out in 2007.DesignCross-sectional population-based study. Dietary assessment was carried out using 48 h recall interviews. A picture book of food portions was used to estimate portion sizes and the national Food Composition Database Fineli® to calculate nutrient intakes.SettingA representative sample taken in five regions in Finland.SubjectsA total of 730 men and 846 women aged 24–64 years.ResultsThe percentage contribution of fat to the total energy intake was 33 % in men and 31 % in women. The respective percentages for SFA in men and women were 13 % and 12 %, respectively, and 0·4 % for trans fatty acids in both genders. The average intakes of folate, vitamin D and fibre fell below the recommended levels, whereas the average salt intake was somewhat higher than the recommendations. Women’s diet was higher in protein, dietary fibre and sucrose compared to that of men.ConclusionsAccording to the FINDIET 2007 Survey, the dietary habits of the adult Finnish population have headed in a positive direction overall. However, although the quality of the fats consumed has continued to improve, and the intake of salt has decreased, they still do not meet the recommended levels of intake. Similarly, the average intakes of folate and vitamin D continue to fall below the recommendations. There is also a need to increase fibre intake and to cut down the intake of sucrose.

scholarly journals Dyslipidemia and Vitamin D Status in Diabetic Patients

2022 ◽  
Vol 05 (01) ◽  
Author(s):  
Mohammed Sassi ◽  
Keyword(s):  
Vitamin D ◽  
Lipid Profile ◽  
Vitamin D Deficiency ◽  
Elevated Serum ◽  
Female Gender ◽  
Serum Levels ◽  
Vitamin D Supplementation ◽  
Diabetic Patients ◽  
Vitamin D Status ◽  
Cross Sectional

Background: Dyslipidemia is one of the most common metabolic syndrome among diabetic patients due to several factors include insulin insufficiency, resistance, and central obesity. Furthermore both vitamin D deficiency and diabetes are most public health worldwide problems. Therefore the aim of the present work to study the dyslipidemia and vitamin D status in diabetes patients and also to study the relation between vitamin D status and lipid profile in diabetic patients. Methods: A Cross sectional study conducted on randomly selected diabetic patients whether have vitamin D deficiency with dyslipidemia, vitamin D deficiency with no dyslipidemia or dyslipidemia with no vitamin D deficiency. A total sample 165 patients enrolled in the study with serum lipid profile, vitamin D and glycemic control measured at beginning and end of the study. The data analysis was done through Chi-square or T test at α< 0.05. Result: The data collected on 165 patients revealed that, patients aged 41-60 years were most common, and female gender was twice as male. This study include both types of diabetes with vitamin D deficiency and dyslipidemia or vitamin D deficiency with no dyslipidemia or dyslipidemia with not vitamin D deficiency as control. Therefore, the result of this work confirmed that vitamin D deficiency significant implicated in elevated serum levels of TG, TC, LDL, VLDL, FPG and HbA1C (P< 0.05). However, vitamin D deficiency has linked to slight increased serum HDL levels. In compared to man, vitamin D deficiency linked significantly to dyslipidemia and abnormal high levels blood glucose and HbA1C par in women. Conclusion: The present study revealed that, vitamin D deficiency associated negatively with serum levels of TC, TG, VLDL, LDL, FPG and HbA1C whereas the deficiency of vitamin D linked to elevated HDL levels. In gender distribution lower vitamin D values associated with elevated serum FPG, HbA1C, lipid profile with exception HDL in women. The data of this study suggested that, diabetic patients with dyslipidemia may improve their lipid profile and glucose hemostasis through vitamin D supplementation

Serum and Bronchoalveolar Lavage Fluid 25(OH)Vitamin D3 Levels in HIV-1 and Tuberculosis: A Cross-Sectional Study from a Tertiary Care Center in North India

2018 ◽  
Vol 16 (2) ◽  
pp. 167-173
Author(s):  
Sanjeev Sinha ◽  
Kartik Gupta ◽  
Dibyakanti Mandal ◽  
B.K. Das ◽  
R.M. Pandey
Keyword(s):  
Vitamin D ◽  
Lavage Fluid ◽  
Cross Sectional Study ◽  
P Value ◽  
Vitamin D Metabolites ◽  
Cross Sectional ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Background: Vitamin D is an immunomodulator, and its deficiency is associated with Tuberculosis (TB) infection. Bronchoalveolar lavage fluid (BALF) is a rich milieu of macrophages that form the first line of defense against invading TB bacilli. As there is an increased prevalence of vitamin D deficiency in TB and human immunodeficiency virus-1 (HIV-1) subjects, we intend exploring the possibility of a localized deficiency of vitamin D metabolites in BALF of these patients. Objective: The primary objective was to assess the level of 25D3 in serum and BALF of subjects and look for a significant difference among patients and controls. The secondary objective was to find a correlation between serum and BALF 25D3 levels. Methods: We performed a cross-sectional study with subjects divided into four groups: Controls (group 1), HIV positive without active TB (group 2), active TB without HIV (group 3), and HIV-TB coinfection (group 4). BALF and serum 25D3 levels were compared between the groups. Results: Among the 149 (an immunomodulator) successive subjects enrolled, there were 40 subjects in group 1 (HIV-TB-), 48 in group 2 (HIV+TB-), 37 in group 3 (HIV-TB+), and 24 in group 4 (HIV+TB+). Females constituted 31.6% of the study subjects. In groups 3 and 4, there were significantly lower serum 25D3 levels compared to group 1 (p-value group 3: 0.002; group 4: 0.012). In groups 2, 3, and 4, there were significantly lower BALF 25D3 levels compared to group 1 (p-value group 2: 0.000; group 3: 0.000; group 4: 0.001). There was a significant correlation between serum and BALF 25D3 levels (Spearman’s rank correlation coefficient 0.318, p-value = 0.0001). Conclusion: Lower levels of serum and BALF 25D3 were observed in HIV, TB, and HIV-TB coinfected patients. Localized deficiency of vitamin D metabolites might be associated with increased vulnerability to TB infection.

scholarly journals Vitamin D status of 51–75-year-old Irish women: its determinants and impact on biochemical indices of bone turnover

2006 ◽  
Vol 9 (2) ◽  
pp. 225-233 ◽  
Author(s):  
Tom R Hill ◽  
Maria M O'Brien ◽  
Christel Lamberg-Allardt ◽  
Jette Jakobsen ◽  
Mairead Kiely ◽  
...  
Keyword(s):  
Vitamin D ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Elevated Serum ◽  
Dietary Calcium Intake ◽  
Vitamin D Status ◽  
Cross Sectional ◽  
Vitamin D Levels ◽  
Serum Pth ◽  
Biochemical Indices

AbstractObjectivesTo assess the vitamin D status of Irish postmenopausal women during wintertime, and to examine its relationship with serum parathyroid hormone (PTH) and biochemical markers of bone turnover. In addition, the determinants of wintertime serum 25-hydroxyvitamin D (25OH–D) levels in these women were investigated.DesignA cross-sectional observational study.SettingCork City, Ireland (52°N).SubjectsNinety-five apparently healthy, free-living postmenopausal women (aged 51–75 years), not taking any medication and free from any condition likely to affect vitamin D status or calcium/bone metabolism.ResultsForty-eight per cent and 7% of women had serum 25OH–D levels <50 nmol l−1and <25 nmol l−1, respectively. 25OH–D levels in these women were positively associated with dietary calcium intake (P= 0.0002) and use of vitamin D-containing supplements (P= 0.031), and negatively associated with cigarette smoking (P= 0.027) and body mass index (BMI) (P= 0.030). Low serum 25OH-D levels (<50 nmol l−1) were associated (P<0.01) with elevated serum PTH levels. There were no significant differences in urinary pyridinium crosslinks or serum osteocalcin, biochemical indices of bone turnover, between subjects with serum 25OH–D levels above or below 50 nmol l−1.ConclusionsA high proportion of Irish postmenopausal women had low vitamin D status (< 50 nmol l−1) during late wintertime, which appeared to lead to elevated levels of serum PTH but not of bone turnover markers. Use of regular low-dose supplemental vitamin D, meeting daily calcium recommendations, cessation of smoking and maintaining BMI in the normal range are important factors that could help maintain adequate vitamin D levels during wintertime in these women.

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