Cause Of Rickets Research Articles

Calcium deficiency and causation of rickets in Ethiopian children

To assess the role of calcium in the development of clinical rickets among Ethiopian children coming to Jimma Specialised Hospital outpatient, department. Case control study. Jimma Specialised Teaching Hospital and surrounding urban and rural community in the catchment area. One hundred and thirty five under five year old children (30 cases of rickets and 104 non-rachitic cases) who came for paediatric service in Jimma hospital. The mean (+/- SD) level of calcium intake for cases and controls was 664.5 (+/- 102.7) mg and 645.8(+/- 144.4) mg, respectively. There was no statistically significance difference between the two groups in the mean level of calcium intake (t = 0.659, P > 0.05). Generally, in both cases and controls the majority of the study participants were taking calcium below the recommended daily calcium requirement of 800 mg for age group according to Food and Nutrition Board of the National Research Council. When adjusted for different co-variates including age, sex, breast feeding history, history of diarrhoea lasting longer than 14 days and 24 hours calcium intake children and religion, occupation, educational status and residence the mothers/care givers using logistic regression model, frequency of exposure to sunlight ( OR = 1.55, 95%CI: 1.2, 2.0), being from rural areas (OR = 5.0, 95% CI: 1.1, 23.3) and age 12-23 months (OR= 4.5, 95% CI: 1.2, 16.5) were significantly associated with rickets (P < 0.05). It was found that Ethiopian children with rickets and without had a low calcium intake as compared to the recommended daily allowance. The fact that there was no difference in the dietary calcium intake between cases and controls and the significant difference observed between case and controls in terms of frequency of exposure to sunlight per week reflects that vitamin D deficiency emanating from poor exposure to radiant energy is the main cause of rickets in Ethiopian children. This study also documented the fact that rural children are at a higher risk of developing rickets as compared to their urban counterparts which could be mainly due to the traditional beliefs and practices more prevalent in the rural areas. Enhancing behaviour change communication about the benefits of exposing children to sunlight is very important in preventing the prevalence of rickets.

Vitamin D deficiency rickets caused by improper lifestyle in Japanese children

Nutritional rickets is considered rare in developed countries. However, reports on vitamin D deficiency rickets caused by improper lifestyle have recently increased. The clinical and laboratory characteristics of patients with vitamin D deficiency rickets treated at Fukuoka Children's Hospital, Fukuoka, Japan, were evaluated to clarify current causes and ways to prevent this disease. Clinical records were reviewed, and obtained information and data were summarized. Eight patients with vitamin D deficiency rickets (five boys and three girls) were treated during the past 10 years (January 1992 to December 2001). Two infants were referred to the hospital for hypocalcemia and convulsion, and six toddlers (1-2 years old) for bowlegs. One patient lacked exposure to sunlight, and six had an unbalanced diet. The cause of rickets could not be established in one patient. Anthropometric and laboratory data did not indicate malnutrition. Serum alkaline phosphatase was 2518.3 +/- 1401.7 IU/l, calcium was 8.2 +/- 2.6 mg/dL (including 4.7 mg/dL in one infant and 4.8 mg/dL in another), and phosphorus was 4.9 +/- 1.0 mg/dL. High sensitive parathyroid hormone was 1393.1 +/- 321.7 pg/mL (reference range, 180-560), 1,25-dihydroxyvitamin D was 86.0 +/- 61.5 pg/mL (reference range, 20-70), and 25-hydroxyvitamin D was 11.6 +/- 5.6 ng/mL (reference range, 10-30). The patients recovered with a change to a balanced diet, the promotion of weaning, and/or an increase in sunlight exposure. Vitamin D deficiency rickets remains a common condition that is best managed by education and disease prevention.

Obstructive uropathy as cause of rickets: Often a forgotten entity

Obstructive uropathy as cause of rickets: Often a forgotten entity

Nutritional rickets: deficiency of vitamin D, calcium, or both?

Nutritional rickets remains a public health problem in many countries, despite dramatic declines in the prevalence of the condition in many developed countries since the discoveries of vitamin D and the role of ultraviolet light in prevention. The disease continues to be problematic among infants in many communities, especially among infants who are exclusively breast-fed, infants and children of dark-skinned immigrants living in temperate climates, infants and their mothers in the Middle East, and infants and children in many developing countries in the tropics and subtropics, such as Nigeria, Ethiopia, Yemen, and Bangladesh. Vitamin D deficiency remains the major cause of rickets among young infants in most countries, because breast milk is low in vitamin D and its metabolites and social and religious customs and/or climatic conditions often prevent adequate ultraviolet light exposure. In sunny countries such as Nigeria, South Africa, and Bangladesh, such factors do not apply. Studies indicated that the disease occurs among older toddlers and children and probably is attributable to low dietary calcium intakes, which are characteristic of cereal-based diets with limited variety and little access to dairy products. In such situations, calcium supplements alone result in healing of the bone disease. Studies among Asian children and African American toddlers suggested that low dietary calcium intakes result in increased catabolism of vitamin D and the development of vitamin D deficiency and rickets. Dietary calcium deficiency and vitamin D deficiency represent 2 ends of the spectrum for the pathogenesis of nutritional rickets, with a combination of the 2 in the middle.

On the adulteration of bread as a cause of rickets. 1857.

On the adulteration of bread as a cause of rickets. 1857.

Metabolic disease in animals.

Rickets is a metabolic bone disorder characterized by osteopenic changes resulting from the failure of calcification of the osteoid matrix and absent mineralization of hypertrophic cartilage cells at the epiphyseal growth plates in growing primates, herbivores, swine, carnivores, and birds. The causes of rickets include inadequate dietary provision of calcium, phosphorus, and vitamin D. Osteomalacia in reptiles, simian bone disease in nonhuman primates, and osteodystrophia fibrosa (secondary hyperparathyroidism) or "bran disease" in herbivores are caused by a diet that has a much higher content of phosphorus than calcium, combined with inadequate exposure to direct sunlight. Medullary bone consists of interconnected spicules of bone resembling embryonic bone and is established in relation to the shell formation cycle of laying birds. Hypertrophic osteodystrophy develops in large-breed growing dogs, chickens, and guinea pigs and is possibly caused by vitamin C deficiency. Tibial dyschondroplasia is a defect in endochondral ossification characterized by a widened proximal tibial physis that is not penetrated by metaphyseal vascular sprouts, commonly found in growing broiler chickens, turkeys, and exotic birds.

Rickets in childhood.

Bone accretion is a two-stage process, with the osteoblasts laying down osteoid, which is then mineralized. Mineralization of osteoid requires vitamin D to be available in its active form (1,25(OH) 2 D); in addition, mineralization also requires normal levels of serum calcium, phosphorus, and alkaline phosphate. Deficiencies of any of these will result in defective mineralization of bone, in which the mineral-osteoid ratio is reduced (a qualitative abnormality). In the juvenile skeleton deficiencies particularly affect enchondral ossification at the growth plates, giving the characteristic clinical and radiological features of rickets. The bone may be soft, leading to deformity. In this article the causes of rickets in childhood are reviewed, together with the clinical and radiological features and strategies for prevention and treatment.

Rickets: it’s not just vitamin D deficiency

Malnutrition of vitamin D and calcium is still the most common cause of rickets and especially in individuals with dark complexions. The capacity of the two renal enzymes in vitamin D metabolism is rather low. Only approximately 10% of 25-hydroxyvitamin D is 24-hydroxylated and 0.3% is 1α-hydroxylated. The activities of these two enzymes are reciprocally controlled by 1,25-dihydroxyvitamin D itself, and vitamin A antagonizes the action of vitamin D. Mutations in the 25-hydroxyvitamin D-1α-hydroxylase gene cause hereditary vitamin D–dependent rickets type I (VDDRI). The domains that are essential for the enzyme activity were identified and are rather selective. X-linked hypophosphatemic rickets is caused by mutations in the PHEX gene and inactivity of the membrane-bound endopeptidase, resulting in impairment of both Na-dependent P-cotransporter and vitamin D metabolism. Likewise, tumor-induced osteomalacia is related to overproduction by a mesenchymal tumor of the putative phosphatonin with remission after resection of the tumor. These disease mechanisms lead to a rational algorithmic approach to diagnosis of rickets.

Final height of Japanese patients with X-linked hypophosphatemic rickets: effect of vitamin D and phosphate therapy.

X-linked hypophosphatemic rickets (XLH) is one of the most common causes of rickets in infancy and childhood. Combination therapy of vitamin D and phosphate is generally used for patients with XLH. Effect of treatment of vitamin D and phosphate during childhood on final height of XLH has to be elucidated in Japanese. There have been only three Caucasian studies on final height of XLH with treatment since childhood. Purpose of this study is to report adult height and therapeutic effect of 22 Japanese participants (5 males, 17 females) with XLH who were treated with phosphate (33-200 mg/kg/day as phosphorus divided into 3 or 4 doses) and vitamin D (vitamin D2 or 1alpha-hydroxyvitamin D3) for more than five years and evaluate effect of the treatment on the final height retrospectively. Final height (FHt) for all participants was -1.69+/-11.11 SD. FHt (-1.69+/-1.11 SD) was significantly higher than height at the initiation of treatment (-2.38+/-0.88 SD) for all participants (P<0.01). In conclusion, combination therapy of vitamin D and phosphate improved final height of Japanese patients with XLH as is similar to previous Caucasian studies.

Genetic causes of rickets.

Dietary deficiency of vitamin D, genetic disorders of its bioactivation to 1,25-dihydroxyvitamin D [1,25(OH)2D], or disorders of vitamin D action can cause rickets. The rate-limiting, hormonally-regulated, biologically activating step in the synthesis of 1,25(OH)2D is the 1 alpha-hydroxylation of 25-hydroxyvitamin D, which occurs in kidney and other tissues and is mediated by a mitochondrial cytochrome P450 enzyme, P450c1 alpha. After many years of effort, the cDNA and gene for this enzyme were cloned in late 1997. Mutations in the P450c1 alpha gene, located on chromosome 12, cause 1 alpha-hydroxylase deficiency, also known as vitamin D-dependent rickets type I, an autosomal recessive disease characterized by rickets and impaired growth due to failure of renal synthesis of 1,25(OH)2D. X-linked hypophosphatemic rickets, a dominantly inherited disease, is caused by mutations in the PHEX gene, whose function in regulating renal phosphate and vitamin D metabolism remains to be elucidated.

The role of the PHEX gene (PEX) in families with X-linked hypophosphataemic rickets.

For over a hundred years, the bane of rickets (a disease of bone), has been prominent in those countries that have participated in, and seeded, the industrial revolution. Industrialisation had major effects of the demography of populations, and many people moved to dark, heavily industrialised cities to find work. It soon became apparent that rickets could be cured by supplementing the diet with cod liver oil and exposure to sunlight. This in turn led to the discovery that photoactivation of 7-dehydrocholesterol was required to produce vitamin D, an indispensable regulator of bone mineral metabolism. Although inadequate exposure to light and poor dietary intake are the main causes of rickets and osteomalacia, recent research has confirmed the role of familial, and tumour forms of the disease. This review will describe the recent advances in our knowledge of the molecular defects in X-linked hypophosphataemic rickets (HYP), and oncogenic hypophosphataemic osteomalacia (OHO). Although HYP and OHO have different primary defects, both diseases have similarities that suggest a linked or overlapping pathophysiology. Also, without doubt, the recent cloning of the gene defective in HYP (the PHEX gene), has given researchers a new reagent to explore the molecular regulation of bone and its links to kidney endocrine function. The fact that the PHEX gene codes for a Zn metallopeptidase raises new and intriguing questions, and adds new momentum to the research on diseases of bone mineral metabolism.

Food-dependent exercise-induced anaphylaxis to corn

J Allergy Clin Immunol 1998;101:853-4.

Vitamin D deficiency rickets in breast‐fed infants presenting with hypocalcaemic seizures

At the Aga Khan Hospital (AKUH), 65 infants presented with hypocalcaemic seizures, subsequently found to have rickets. Forty-six infants less than 6 months were totally or predominantly breast fed. In a subgroup of 15 mothers and their infants, we found very low plasma levels of 25(OH) vitamin D of < 5 micrograms/l and 7.5 +/- 3.3 micrograms/l, respectively. Neither mothers nor infants received vitamin D supplementation. Maternal vitamin D deficiency and non-supplementation in the infants were the likely causes of rickets in our patients. Prophylactic vitamin D 400 i.u. administered to infants up to 2 years and 800 i.u. to women in pregnancy and during lactation is recommended to prevent vitamin D deficiency.

Lesson of the Week: Hypocalcaemic stridor and infantile nutritional rickets

Nutritional deficiency of vitamin D is considered to be a rare cause of rickets in industrialised countries, mainly because vitamin D is added routinely to formula feeds for infants.1 2 Human breast milk, however, may be deficient in vitamin D, and exclusively breast fed infants who have not received vitamin supplements are at risk. Otherwise well nourished infants may not have the obvious or typical bony deformities of rickets but may present with the symptoms of hypocalcaemia. We describe two infants who presented with stridor and intermittent sudden airway obstruction due to laryngospasm. Both infants had severe hypocalcaemia due to nutritional deficiency of vitamin D. ### CASE 1 A 5 month old black boy weighing 7.5 kg was taken to the accident and emergency department at Queen Elizabeth Hospital for Children with a one month history of intermittent laboured and noisy breathing. The boy's respiratory distress had often been accompanied by generalised rigidity, convulsions, and cyanosis and had usually occurred when he was crying. He was taken to the hospital because he had become apnoeic at home and had been given mouth to mouth resuscitation by his mother. Just after he was …

The Effect of Phosphate Supplementation on Linear Growth in Children with X-Linked Hypophosphatemia

X-linked hypophosphatemia is the most common inherited cause of rickets. Current therapy for this disorder includes vitamin D and phosphate supplementation; however, phosphate therapy has been associated with nephrocalcinosis. The purpose of this study is to evaluate the effect of oral phosphate therapy on growth in patients with X-linked hypophosphatemia treated with either calcitriol or dihydrotachysterol (vitamin D). We retrospectively evaluated the prepubertal growth of 36 children with X-linked hypophosphatemia. The height standard deviation score (Z-score) of patients initially treated with vitamin D alone and the Z-scores of patients treated with vitamin D and phosphate therapy were compared. In addition, the growth of therapy were compared. In addition, the growth of patients treated with vitamin D was compared with that of patients treated with vitamin D and phosphate from the outset of therapy. Patients treated with vitamin D alone for 5.36 +/- 2.18 years had an improvement in Z-score from -3.1 +/- 1.10 to -2.49 +/- 0.66 SDS, P < .05. Adding phosphate therapy for patients initially treated with vitamin D alone for 4.83 +/- 2.99 years did not further improve Z-score (-2.49 +/- 0.66 vs -2.35 +/- 0.83). Initial therapy with vitamin D and phosphate for 4.33 +/- 2.19 years also improved Z-score, (-2.84 +/- 1.02 vs -1.98 +/- 0.82, P < .05). The change in Z-score was similar to the group treated with vitamin D alone compared with the group treated initially with vitamin D and phosphate (0.65 +/- 0.54 vs 0.85 +/- 0.65, respectively). These data demonstrate that both vitamin D alone and in combination with phosphate improved linear growth. Adding oral phosphate for children initially treated with vitamin D alone did not improve Z-score. Initial therapy with vitamin D and vitamin D plus phosphate produced similar changes in linear growth.

A possible genetic defect in 25-hydroxylation as a cause of rickets

We examined two siblings who had severe rickets at ages 2 and 7 years, respectively, despite a history of adequate vitamin D intake. The patients' sera had calcium concentrations at the lower limits of normal, low phosphate concentrations, elevated alkaline phosphatase activity, and low levels of 25-hydroxyvitamin D. Treatment with high doses of vitamin D2 resulted in resolution of the biochemical abnormalities and radiographic deformities; pharmacologic doses of vitamin D2 were required to maintain normal concentrations of 25-hydroxyvitamin D in the serum even though vitamin D absorption was normal. These children may have a genetic defect of the 25-hydroxylation step in vitamin D activation.

Idiopathic Fanconi syndrome in a family. Part I. Clinical aspects.

Fanconi syndrome is a rare cause of rickets in children. Only six families with Fanconi syndrome following an autosomal dominant pattern of inheritance have been reported. In this report, the results of clinical studies performed in three generations of a family of 39 members with autosomal dominant Fanconi syndrome are presented. Twenty-one members of this family provided blood and urine for biochemical evaluation. Many family members have one or more tubular reabsorptive abnormalities; however, the complete Fanconi syndrome was not present in most members. Three children with the complete syndrome all occur in the last generation. When the characteristic features of this family were compared with those of previously reported families with autosomal dominant Fanconi syndrome, several differences became apparent. Two serious manifestations, diabetes mellitus and renal failure, which occur in previous reports did not occur in this family. This report provides information on apparently the largest number of affected individuals in a single family with Fanconi syndrome. In addition, variable expressivity of tubular reabsorptive defects in a family with Fanconi syndrome has never been reported.

Convulsions as a Possible Manifestation of Vitamin D Deficiency Rickets in Infants One to Six Months of Age

During the 42 months of January 1985 through June 1988, five infants between the ages of one and six months had hypocalcemic convulsions associated with vitamin D deficiency rickets. Despite abundant sunlight, convulsions as a manifestation of vitamin D deficiency in young infants are not uncommon in Saudi Arabia and should be considered as a probable cause for hypocalcemic seizure in breast fed infants.

FREQUENCY OF RICKETS IN INFANCY IN BOSTON IN 1898

Classic cases of rickets are now rarely seen in the pediatric practice of Boston physicians. But 90 years ago, 8 out of 10 infants under 2 years of age, seen at the Boston Infants' Hospital, were found to have had rickets, as noted below. Four hundred consecutive infants under two years of age, medical out-patients at the Infants' Hospital, were examined for evidences of rickets. Eighty percent showed more or less marked signs. A rosary was present in every case. Only those enlargements were considered as a rosary which could be felt both parallel and vertical to the long axis of the rib. It was the only symptom in 40 percent. It was accompanied by but one other symptom in 20 percent. The single associated symptom was most often delayed dentition, next, enlargement of the cranial eminences. Delayed dentition occurred in more than 50 percent. Large fontanelle, large eminences, retraction at the diaphragm, and the enlargement of the epiphyses of the extremities were each present in about 15 per cent but were symptoms of later development. Marked rhachitic deformities were rare. About 40 percent of the cases were Russian and Polish Jews. Only 12 per cent came from the southern races. Breast milk was a part of the diet in 43 per cent and formed the whole in 18 per cent. The only influence acting on all alike was improper hygienic surroundings. These therefore must be considered as the most potent cause of rickets in Boston and vicinity.

Magnesium‐deficient rickets in a phenylketonuric patient on dietary treatment

Absolute or relative vitamin D deficiency is the most frequent cause of rickets in children. Many reviews have shown that rickets may appear in association with environmental conditions, wrong dietary habits, gastrointestinal diseases and drug administration. Magnesium deficiency is also an uncommon cause of rickets. We report the case of a phenylketonuric (PKU) child with vitamin D-resistant rickets and magnesium deficiency.