The burden of vitamin D deficiency in household members of children presenting with symptomatic vitamin D deficiency

BACKGROUND: Micronutrient deficiencies are common among household/family members due to shared lifestyle and dietary habits. The extent of biochemical abnormalities in household members of children presenting with symptomatic vitamin D deficiency remains unknown. AIM: Investigate the prevalence of vitamin D deficiency and biochemical osteomalacia in the mothers and siblings of children presenting with symptomatic vitamin D deficiency. METHODS: All mothers and sibling of children referred to a single tertiary endocrine centre between January 2018 and December 2021, with symptomatic vitamin D deficiency were investigated prospectively for vitamin D deficiency [defined as 25 hydroxyvitamin D (25OHD) < 30nmol/L] and biochemical osteomalacia [vitamin D deficiency and elevated alkaline phosphatase (ALP) and/or parathormone (PTH)] as per clinical guidelines. REULTS: Ninety-seven family members (68 siblings and 29 mothers) of 29 index cases (median age 1.7 years, 55.5% male) were investigated. The majority (65.5%, n=19) were of Asian ethnic background. The mean (SD) 25OHD levels of the index, maternal and sibling cohorts were 15 (10), 15 (7) and 20 (10) nmol/L respectively. Vitamin D deficiency was noted in 93% of the maternal and 79% of the sibling cohorts. Biochemical osteomalacia was present in 72% of the maternal and 79% of the sibling cohorts. Mothers of infants had significantly lower mean 25OHD levels compared to mothers of older children [11 (n=12) vs 18 nmol/L (n=17) respectively, p=0.006)], most of whom were symptomatic (66.6%, n=8/12). None of the mothers had hypocalcaemia. Among the 10% (n=7) of the siblings with hypocalcaemia, 86% (n=6/7) had concurrent dietary calcium deficiency and 71.4% (n= 5/7) reported symptoms in retrospect. Hypocalcaemic siblings had significantly lower 25OHD (7 vs 15 nmol/L, p<0.001), higher PTH (175 vs 58 ng/L, p<0.001) and ALP (846 vs 318 IU/L, p<0.001), respectively compared to normocalcaemic siblings. CONCLUSIONS: In view of the substantial morbidity uncovered in household/family members of children diagnosed with symptomatic vitamin D deficiency, we recommend universal supplementation of all risk groups. Biochemical testing and treatment is indicated to replenish stores only in those at highest risk such as mothers of infants, individuals with concurrent dietary calcium deficiency and those with clinical symptoms

Oral iron for prevention and treatment of rickets and osteomalacia in autosomal dominant hypophosphatemia

Autosomal dominant hypophosphatemia (ADH) causes rickets, osteomalacia, and taurodontism due to heterozygous mutations in FGF23, which inhibit the inactivation (cleavage) of the encoded protein, the hormone fibroblast growth factor 23 (FGF23). Iron deficiency increases FGF23 mRNA expression and recent evidence suggests that the recurrent, lateonset, or waxingwaning hypophosphatemic phenotype may be linked to synchronous variations in iron status. The fact that most adult symptomatic ADH patients are females during reproductive age supports the notion of a geneenvironmental interaction. Practically all symptomatic hypophosphatemic patients described in the recent literature were also iron deficient (with/without anemia) at presentation, when measured. Given its interaction with FGF23, correcting iron deficiency should therefore also correct FGF23 excess. Following the original report of successful phenotype reversal in an irondeficient ADH child using oral iron supplementation in 2015, more evidence has emerged that supports the use of the element iron to restore homoeostasis of the element phosphorus (in addition to its own). We put into perspective the recent evidence and add 14 years observational data on the original case that demonstrates the correlation of serum phosphorus and renal tubular phosphate reabsorption in mass per unit volume of glomerular filtrate (TmP/GFR) with serum ferritin. Presentation and relapse of ADH, 12 years apart, occurred during iron deficiency, and the onset of menstrual periods was associated with relapse. Here we propose management guidance for patients affected by ADH throughout the lifespan based on iron stores. Because ferritin correlates best with hypophosphatemia historically, and in longterm observation of the originally treated case, it should be used as the monitoring tool and kept in the normal range. Women with ADH who are of reproductive age and other risk groups require supplementation with oral iron using WHO guidelines. Treatment of this form of FGF23 excess may not require phosphate and active vitamin D, or burosumab.(VLID)4844491Version of recor

Prevention of rickets and osteomalacia in the United Kingdom:Political action overdue

The consequences of vitamin D and dietary calcium deficiency have become a huge public health concern in the UK. The burden of disease from these deficiencies includes rickets, and hypocalcaemic seizures, dilated cardiomyopathy and mostly occult myopathy and osteomalacia. The increasing burden of the disease is intrinsically linked to ethnicity and the population demographic changes in the UK. Three facts have led to the resurfacing of the English disease: (1) the UK has no ultraviolet sunlight for at least 6 months of the year, (2) dark skin produces far less vitamin D than white skin per unit ultraviolet light exposure, and (3) non-European Union immigration over the last century. To date, the UK government demonstrates incomplete understanding of these three facts, and its failure to adjust its prevention programmes to changing demographics is endangering the health and life of UK residents with dark skin, of whom infants are the most vulnerable. Establishing accountability through the implementation of monitored antenatal and infantile supplementation programmes and mandatory food fortification is overdue.</jats:p

Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study

<p>Abstract</p> <p>Background</p> <p>Age- and sex-specific reference intervals are an important prerequisite for interpreting thyroid hormone measurements in children. However, only few studies have reported age- and sex-specific pediatric reference values for TSH_basal(TSH), free T3 (fT3), and free T4 (fT4) so far. Reference intervals are known to be method- and population-dependent. The aim of our study was to establish reference intervals for serum TSH, fT3, and fT4 from birth to 18 years and to assess sex differences.</p> <p>Methods</p> <p>2,194 thyroid hormone tests obtained from a hospital-based pediatric population were included into our retrospective analysis. Individuals with diagnoses or medications likely to affect thyroid function were primarily excluded, as well as the diagnostic groups, if different from the purely healthy subgroup (n = 414). Age groups were ranging from 1 day to 1 month, 1 – 12 months, and 1 – 5, 6 – 10, 11 – 14, and 15 – 18 years, respectively. Levels of fT3, fT4 and TSH were measured on Advia^®Centaur™ automated immunoassay system.</p> <p>Results</p> <p>The final sample size for reference data creation was 1,209 for TSH, 1,395 for fT3, and 1,229 for fT4. Median and 2.5/10/25/75/90/97.5 percentiles were calculated for each age group. Males had greater mean fT3 concentrations than females (p < 0.001). No sex-differences were found for TSH and fT4 between age-matched serum samples. Median concentrations of fT3, fT4 and TSH were greatest during the first month of life, followed by a continuous decline with age.</p> <p>Conclusion</p> <p>Our results corroborate those of previous studies showing that thyroid hormone levels change markedly during childhood, and that adult reference intervals are not universally applicable to children. Moreover, differences of our reference intervals compared to previous studies were observed, likely caused by different antibody characteristics of various analytical methods, different populations or undefined geographic covariates, e.g. iodine and selenium status.</p