Dependent Rickets Type Research Articles

Seizure as a presenting manifestation of vitamin D dependent rickets type 1.

Seizure as a presenting manifestation of vitamin D dependent rickets type 1.

High FGF23 measurements in a child with vitamin D dependent rickets type I: cause or consequence?

High FGF23 measurements in a child with vitamin D dependent rickets type I: cause or consequence?

Vitamin D dependent rickets type 1 (VDDR-1): two years after discontinuation of treatment

Vitamin D dependent rickets type 1 (VDDR-1): two years after discontinuation of treatment

Vitamin D Dependent Rickets Type II with Alopecia

As a test of the effects of age and information load Ss performed a visual and auditory discrimination task under conditions requiring division of attention. Amount of stimulus information was determined by the number of stimulus alternatives which could occur in a set of trials. Performance by 12 Ss over age 40 was impaired in comparison to 12Ss under age 40. Performance for all Ss was a function of amount of information, but there was no Age X Information Load interaction. It has been reported in the literature that age-related performance decrements are correlated with task complexity. These data indicate that amount of information is not a critical dimension of task complexity as it contributes to age-related performance deficits.

Vitamin D dependent rickets type 1: 2 years after discontinuation of treatment

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

High FGF23 measurements in a child with vitamin D dependent rickets type I: cause or consequence?

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

No evidence of association between mutant alleles of the CYP27B1 gene and multiple sclerosis

An association has previously been reported between susceptibility to multiple sclerosis and the rare mutant alleles of the CYP27B1 gene responsible for autosomal recessive vitamin D–dependent rickets type 1 (VDDR1). In an attempt to replicate this finding, we screened 495 multiplex families and 2,092 single affected families, together with 4,594 cases and 3,583 controls (a total of 17,073 individuals) but were unable to find any evidence supporting this putative association. Our data do not indicate that mutations responsible for VDDR1 influence the risk of developing multiple sclerosis. ANN NEUROL 2013;73:430–432

Clinical and genetic analysis of patients with vitamin D‐dependent rickets type 1A

Vitamin D-dependent rickets type 1A (VDDR-IA, OMIM 264700) is a rare autosomal recessive disorder and is caused by mutations in the CYP27B1 gene. We aim to investigate CYP27B1 mutation in seven patients from four separate families and characterize the genotype-phenotype correlation. The entire coding region of the CYP27B1 gene was sequenced, and genotype-phenotype correlation among patients was assessed. Sequencing analysis identified biallelic CYP27B1 mutations in all patients and monoallelic mutations in their parents. One patient from the first family was compound heterozygous for c.1166G>A (p.Arg389His) and a novel nonsense mutation c.1079 C>A (p.Ser360*). Two patients from the second family were homozygous for a novel splice donor site mutation in intron 1 (c.195+2 T>G), causing partial retention of the intron and a shift in the reading frame. Both novel mutations lead to the complete loss of vitamin D1α-hydroxylase activity. Four patients from families 3 and 4 were homozygous for a previously reported duplication mutation in exon 8 (1319-1325dupCCCACCC, Phe443Profs*24). Interestingly, one patient who was presented with severe hypocalcaemia and seizures at 4months of age as a result of Phe443Profs*24 has improved spontaneously since 11years of age and does not need regular treatment. Her laboratory tests showed normal serum calcium and 1,25(OH)(2) D after refusing to take medication for 12months. There is a good genotype-phenotype correlation in VDDR-IA. However, some patients may recover from the loss of CYP27B1 function, probably due to 1α-hydroxylase activity exerted by a non-CYP27B1 enzyme.

Vitamin D dependent rickets(Type 1) due to autoimmune injuries to the kidney and muscles cured by a low dose of prednisone: 5 years following up

Vitamin D dependent rickets(Type 1) due to autoimmune injuries to the kidney and muscles cured by a low dose of prednisone: 5 years following up

Vitamin D dependent rickets, diagnostic and therapeutic difficulties: two case reports

There are two types of vitamin D dependent rickets (VDDR) that cause rickets in children. Vitamin D dependent rickets type 1 (VDDR-I) is caused by an inborn error of vitamin D metabolism, which interferes with renal conversion of calcidiol (25OHD) to calcitriol (1,25(OH)2D) by the enzyme 1alpha-hydroxylase. Vitamin D dependent rickets type 2 (VDDR-II) is caused by a defect in the vitamin D receptor (VDR). We report cases of two African children affected by VDDR-I and VDDR-II, respectively. Establishing an early diagnosis of these genetic forms of rickets is challenging, especially in developing countries where nutritional rickets (NR) is the most common variety of the disease. A prompt diagnosis is necessary to initiate adequate treatment, resolve biochemical features and prevent complications, such as severe deformities that may require surgical intervention.

Vitamin D dependent rickets type I

Vitamin D is present in two forms, ergocalciferol (vitamin D2) produced by plants and cholecalciferol (vitamin D3) produced by animal tissues or by the action of ultraviolet light on 7-dehydrocholesterol in human skin. Both forms of vitamin D are biologically inactive pro-hormones that must undergo sequential hydroxylations in the liver and the kidney before they can bind to and activate the vitamin D receptor. The hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D], plays an essential role in calcium and phosphate metabolism, bone growth, and cellular differentiation. Renal synthesis of 1,25(OH)2D from its endogenous precursor, 25-hydroxyvitamin D (25OHD), is the rate-limiting and is catalyzed by the 1α-hydroxylase. Vitamin D dependent rickets type I (VDDR-I), also referred to as vitamin D 1α-hydroxylase deficiency or pseudovitamin D deficiency rickets, is an autosomal recessive disorder characterized clinically by hypotonia, muscle weakness, growth failure, hypocalcemic seizures in early infancy, and radiographic findings of rickets. Characteristic laboratory features are hypocalcemia, increased serum concentrations of parathyroid hormone (PTH), and low or undetectable serum concentrations of 1,25(OH)2D despite normal or increased concentrations of 25OHD. Recent advances have showed in the cloning of the human 1α-hydroxylase and revealed mutations in its gene that cause VDDR-I. This review presents the biology of vitamin D, and 1α-hydroxylase mutations with clinical findings.

Raquitismo vitamina D dependente tipo II.

Rickets is a rare child disease especially in developed countries. Nutritional rickets remains the most prevalent condition, although congenital forms are well known. In the latest group, vitamin D dependent rickets type II is the rarest form and it can course with or without alopecia. There is a mutation on the receptor for vitamin D, with peripheral resistance to the vitamin D action. The authors present two clinical cases of vitamin D dependent rickets type II, in which the alopecia was a peculiar clinical sign that allowed the diagnoses. With prolonged calcium infusions, we achieved normal seric levels of calcium and correct bone disorders; alopecia persisted. This treatment is the most effective way to control the disease.

Celiac disease and vitamin D dependent rickets type I. Case report

Celiac disease and vitamin D dependent rickets type I. Case report

Diffuse osteopenia and myelopathy in a puppy fed a diet composed of an organic premix and raw ground beef

An 8-month-old Shetland Sheepdog was evaluated because of the sudden onset of signs of neck pain, collapse, and inability to rise. A cursory diet history indicated that the dog had been fed a raw meat-based diet. Initial evaluation of the dog revealed small physical stature, thin body condition, and signs of cranial cervical myelopathy. Radiographically, diffuse osteopenia of all skeletal regions was identified; polyostotic deformities associated with fracture remodeling were observed in weight-bearing bones, along with an apparent floating dental arcade. Hypocalcemia and hypophosphatemia were detected via serum biochemical analyses. The dog's diet was imbalanced in macronutrients and macrominerals. The dog received supportive care and treatment of medical complications; neurologic abnormalities improved rapidly without intervention. Dietary changes were implemented during hospitalization, and a long-term feeding regimen was established. Following discharge from the hospital, exercise restriction was continued at home. Serial follow-up evaluations, including quantitative bone density measurements, revealed that dietary changes were effective. After 7 months, the dog was clinically normal. In the dog of this report, vitamin D-dependent rickets type I and suspected nutritional secondary hyperparathyroidism developed following intake of a nutritionally incomplete and unbalanced diet. The raw meat-based, home-prepared diet fed to the dog was not feed-trial tested for any life stage by the Association of American Feed Control Officials, and its gross nutrient imbalance induced severe metabolic, orthopedic, and neurologic abnormalities. Inadvertent malnutrition can be avoided through proper diet assessment and by matching nutrient profiles with patients' nutritional needs.

Targeted ablation of the 25-hydroxyvitamin D 1alpha -hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction.

The active form of vitamin D, 1alpha,25-dihydroxyvitamin D [1alpha,25(OH)2D], is synthesized from its precursor 25 hydroxyvitamin D [25(OH)D] via the catalytic action of the 25(OH)D-1alpha-hydroxylase [1alpha(OH)ase] enzyme. Many roles in cell growth and differentiation have been attributed to 1,25(OH)2D, including a central role in calcium homeostasis and skeletal metabolism. To investigate the in vivo functions of 1,25(OH)2D and the molecular basis of its actions, we developed a mouse model deficient in 1alpha(OH)ase by targeted ablation of the hormone-binding and heme-binding domains of the 1alpha(OH)ase gene. After weaning, mice developed hypocalcemia, secondary hyperparathyroidism, retarded growth, and the skeletal abnormalities characteristic of rickets. These abnormalities are similar to those described in humans with the genetic disorder vitamin D dependent rickets type I [VDDR-I; also known as pseudovitamin D-deficiency rickets (PDDR)]. Altered non-collagenous matrix protein expression and reduced numbers of osteoclasts were also observed in bone. Female mutant mice were infertile and exhibited uterine hypoplasia and absent corpora lutea. Furthermore, histologically enlarged lymph nodes in the vicinity of the thyroid gland and a reduction in CD4- and CD8-positive peripheral T lymphocytes were observed. Alopecia, reported in vitamin D receptor (VDR)-deficient mice and in humans with VDDR-II, was not seen. The findings establish a critical role for the 1alpha(OH)ase enzyme in mineral and skeletal homeostasis as well as in female reproduction and also point to an important role in regulating immune function.

Genetics of vitamin D biosynthesis and its disorders.

The principal hormone regulator of bone mineralization is vitamin D, which must be activated by a metabolic pathway consisting of a 25-hydroxylase and a 1alpha-hydroxylase to yield 1,25 (OH)(2)D. The hormonal regulation of vitamin D activation is at the level of the 1alpha-hydroxylase. We review the biology of vitamin D, the biochemistry of its activation and the molecular biology of the vitamin D-metabolizing enzymes. Recent advances have resulted in the cloning of the human vitamin D 1alpha-hydroxylase and the identification of mutations in its gene that cause Vitamin D Dependent Rickets type I.

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.

GENETIC DISORDERS OF VITAMIN D BIOSYNTHESIS

The principal hormonal regulator of bone mineralization is vitamin D, which must be activated by a metabolic pathway consisting of a 25-hydroxylase and a 1 alpha-hydroxylase to yield 1,25 dihydroxy vitamin D. The hormonal regulation of vitamin D activation is at the level of the 1 alpha-hydroxylase. This article reviews the biology of vitamin D, and describes the biochemistry of its activation and the molecular biology of the vitamin D-metabolizing enzymes. Recent advances, principally in the authors' laboratories, have resulted in the cloning of the human vitamin D 1 alpha-hydroxylase and the identification of mutations in its gene that cause Vitamin D Dependent Rickets type I.

Implantable central venous access devices in children with metabolic disease

We have inserted 20 totally implantable central venous devices in 17 patients with severe metabolic disease over a 43-month span. Patient ages ranged from 2 months to 17 years (mean, 4.2 years). The underlying pathology was Gaucher's disease in six patients, vitamin D—dependent rickets type II in five, propionic acidemia in two, and methylmalonic acidemia, 3-hydroxyl-3-methylglutaryl coenzyme A (CoA) lyase deficiency, fructose 1,6-diphosphatase deficiency, and urea cycle disorder in one child each. There were seven complications (six due to catheter-related infection and one due to occlusion of the system) during a total of 7,278 patient-catheter days. The infection rate was 0.8 per 1,000 days. Six catheters were removed due to complications and two due to completion of treatment. There were no operative complications or deaths. Our experience demonstrates that a totally implantable device may be useful in children with metabolic disease who need long-term venous access. Attention should be given to minimize the infection rate to reduce the rate of catheter removal.

Vitamin D 3 elicits calcium response and activates blood monocyte-derived macrophages from patients with vitamin D dependent rickets type II

We studied the effects of vitamin D 3 metabolites on intracellular free Ca 2+ concentration ([Ca 2+] i) and the respiratory burst of monocyte-derived macrophages (MDM) from patients with vitamin D dependent rickets type II. Treatment of MDM from the patients and healthy donors with 1 nM 1,25(OH) 2D 3 produced a rapid elevation of [Ca 2+] i and similarly primed both types of cells for enhanced capacity for O 2 − release with phorbol diester. These results suggest that macrophages may have distinct non-genomic pathways of vitamin D 3, which partly explain the absence of immunodeficiency and the disappearance of rickets after treatment with vitamin D 3 in the patients.