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Мета: визначити вплив консервативної терапії на генетично зумовлені порушення метаболізму кісткової тканини у хворих на вітамін-D-залежний рахіт (ВDЗР) І типу. Матеріал і методи. На базі консультативно-поліклінічного відділу ДУ «Інститут травматології та ортопедії НАМНУ» було обстежено та проліковано 48 пацієнтів із діагнозом «вітамін-D-залежний рахіт І типу». Консервативне лікування пацієнтів з рахітоподібними захворюваннями проводилось в 4 етапи. Перший етап включав в себе повне обстеження пацієнта на кальцій, фосфор крові та сечі, визначення рівня кальцидіолу та кальцитріолу крові, показників паратиреоїдного гормона та остеокальцину, а також маркера кісткоутворення P1NP і остеорезорбції B-CTx. На першому етапі в обов’язковому порядку діти проходили генетичне дослідження для виявлення змін (поліморфізму) в алелях рецепторів до вітаміну D та колагену першого типу. Обстеження на наступних етапах проводилось в повному обсязі, окрім генетичних досліджень. Результати. Всебічне вивчення метаболізму вітаміну D і біохімічних показників життєдіяльності кісткової тканини у хворих на ВDЗР І типу дозволило впритул підійти до розуміння деяких питань патогенезу та сутності остеомаляційних і в подальшому остеопоротичних змін різного ступеня, об’єктивувати ці зміни у відповідних показниках біохімічного дослідження та залежно від змін розробити різні схеми медикаментозної корекції порушень кісткового обміну за даного захворювання. Висновки. Для медикаментозного лікування ВDЗР І типу альфакальцидол є препаратом вибору, бо має можливість трансформуватись печінкою в кальцитріол, обійшовши генетично пошкоджене ниркове 1α-гідроксилювання. На підставі вивчення біохімічних показників у пацієнтів з вітамін-D-залежним рахітом І типу розроблено патогенетично обґрунтовану ефективну медикаментозну терапію ортопедичних проявів, що включає холекальциферол (80 000 Од/міс) та альфакальцидол (7,5 мкг/міс). Запропоноване лікування дає значне покращення метаболізму кісткової тканини, що відображається в біохімічних і клінічних показниках вже після першого 3-місячного етапу лікування (p < 0,05).

The term "vitamin D dependent rickets" describes a group of genetic disorders that are characterized by early-onset rickets due to the inability to maintain adequate concentrations of active forms of vitamin D or a failure to respond fully to activated vitamin D. Although the term is now admittedly a pathophysiological misnomer, there remains clinical relevance for its continued use, as patients have a lifelong "dependency" on administration of specialized regimens of vitamin D replacement. This review provides an update on the molecular bases for the three forms of vitamin D dependent rickets, and summarizes current protocols for management of affected subjects.

Rickets is a metabolic bone disease that develops as a result of inadequate mineralization of growing bone due to disruption of calcium, phosphorus and/or Vitamin D metabolism. In addition, several rare genetic causes of rickets have also been described, which can be divided into two groups. The first group consists of genetic disorders of Vitamin D biosynthesis and action, such as Vitamin D-dependent rickets Type 1A, Type 1B, Type 2A (VDDR2A) and Type 2B. The second group involves genetic disorders of excessive renal phosphate loss (hereditary hypophosphatemic rickets). VDDR2A is a rare autosomal recessive disorder caused by mutation in the Vitamin D receptor gene, leading to end-organ resistance to 1,25(OH)2 Vitamin D3. It clinically represents growth retardation presenting in the 1st year of life and frequently associated with alopecia totalis, which differentiates it from VDDR Type 1. Due to target organ resistance, its response to Vitamin D is poor. We report two cases of familial VDDR2A, with alopecia and oral manifestations.

The review summarizes clinical features, biochemical and molecular-genetic characteristics, laboratory and instrumental indicators, as well as approaches to the treatment of ricket-like diseases: vitamin D-dependent rickets, renal tubular acidosis, de Toni-DebreFanconi syndrome. Differential diagnosis of this disease group is associated with a number of difficulties, the main of which are a fairly low frequency of certain forms occurrence and a strong resemblance with other diseases, that disrupt the metabolism, associated with the influence of many hereditary and external factors. Establishing an accurate diagnosis is important not only for correct and timely treatment, but also for medical-genetic family counseling and genetic risk calculation, since different disease forms have different inheritance types. A competent and timely diagnosis should be based on knowledge of the distinctive features of very similar diseases. The data described in this article can be used by doctors at all stages of the patient survey.

Rickets is a defect of bone mineralization caused by vitamin D deficiency, seen most significantly at growth plates that result in radiological bony abnormalities like metaphyseal flaring and cupping, physeal widening with focal and generalised osteomalacia. Here we present a rare case of 7 years old male, a case of vitamin D3 deficiency rickets in a known case of multi drug resistant pulmonary tuberculosis. The patient had suffered left proximal fibular fracture following trivial fall 1.5 month back and had delayed bony union leading to difficulty in walking and pain. The patient was treated with oral vitamin D supplementation. In vitamin D deficiency rickets, there is decreased bone mineralization leading to weak bones and delayed fracture healing in children. Low serum vitamin D levels also caused decreased immunity with increased susceptibility to respiratory infections like pulmonary tuberculosis. Appropriate treatment with injectable or oral vitamin D3 with adequate exposure of sunlight and proper nutrition is the best modality of treatment.

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Rickets is softening of bones due to defective mineralization of cartilage in the epiphyseal growth plate, leading to widening of ends of long bones, growth retardation, and skeletal deformities in children. The predominant cause is deficiency or impaired metabolism of vitamin D. The observation that some forms of rickets could not be cured by regular doses of vitamin D, led to the discovery of rare inherited abnormalities of vitamin D metabolism or vitamin D receptor. Vitamin D dependent rickets (VDDR) is of two types: Type I is due to defective renal tubular 25-hydroxyvitamin D 1-α hydroxylase and type II is due to end-organ resistance to active metabolite of vitamin D. Typical signs are observed from the first month of life. The patient with rickets described below had markedly increased serum alkaline phosphatase and 1,25-dihydroxyvitamin D. We attribute these abnormalities to impaired end-organ responsiveness to 1,25-dihydroxyvitamin D.

Rickets is an important problem even in countries with adequate sun exposure. The causes of rickets/osteomalacia are varied and include nutritional deficiency, especially poor dietary intake of vitamin D and calcium. Non-nutritional causes include hypophosphatemic rickets primarily due to renal phosphate losses and rickets due to renal tubular acidosis. In addition, some varieties are due to inherited defects in vitamin D metabolism and are called vitamin D dependent rickets. This chapter highlights rickets/osteomalacia related to vitamin D deficiency or to inherited defects in vitamin D metabolism. Hypophosphatemic rickets and rickets due to renal tubular acidosis are discussed in other sections of the journal.

Measurement of 1,25(OH)2D, the most biologically active form of vitamin D, circulating levels is relevant in several physiopathological states such as chronic kidney disease, parathyroid dysfunction, sarcoidosis, and vitamin D dependent rickets. Our study determined the performances of a novel automated 1,25(OH)2D immunoassay in a core-laboratory environment. We observed satisfactory analytical performances for this assay and an excellent agreement with a well established LC-MS/MS method. Furthermore, this assay allows a reduced TAT, integration in automated core-laboratories and potential consolidation with other tests of the bone and mineral metabolism.

Hintergrund: Trotz Rachitisprophylaxe tritt die Vitamin-D-Mangel-Rachitis (VDR) in Deutschland noch immer relativ haufig auf. Aufgrund der Untersuchung eines grosen Patientenkollektivs werden aktuelle Aspekte zur Haufigkeit, Atiologie, Pathophysiologie und Diagnostik der VDR dargestellt. Methode: In einer retrospektiven Studie von 1989–1999 wurden 182 unbehandelte Kinder und Jugendliche mit gesicherter VDR erfasst und 4 verschiedenen Gruppen zugeordnet: 1. klassische Rachitis (n=115), 2. Antikonvulsivarachitis (n=16), 3. Rachitis bei schwerer Behinderung (n=27) und 4. so genannte Immigrantenrachitis (n=24). In den Seren aller und in den gleichzeitig gewonnenen Morgenurinproben der meisten Patienten wurden zahlreiche Parameter des Kalzium-, Knochen- und Vitamin-D-Stoffwechsels mit Hilfe etablierter Methoden untersucht. Ergebnisse: Das mediane Alter betrug in den 4 Gruppen 13 Monate, 7,8 Jahre, 9 Jahre und 13 Jahre. Die klassische VDR (Gruppe 1) betraf vorwiegend Jungen (75 von 115 Kindern), die Immigrantenrachitis (Gruppe 4) vorwiegend Madchen (20 von 24 Kindern), wahrend fur die beiden anderen Gruppen keine Geschlechtsabhangigkeit bestand. Unter Berucksichtigung der von den einsendenden Kliniken versorgten Kinder ergab sich fur die VDR in Deutschland weiterhin eine hohe Inzidenz von uber 400 Fallen/Jahr. Eine Auswertung der Laborparameter der homogensten und grosten Patientengruppe, namlich der Kinder mit klassischer VDR, ergab folgende Ergebnisse: Jeder 2. Patient hatte eine Hypokalzamie und jeder 5. Patient einen z. T. lebensbedrohlichen hypokalzamischen Krampfanfall. Die Serumkonzentrationen von Kalzium und Parathormon der hypokalzamischen Patienten mit und ohne Krampfanfalle unterschieden sich nicht signifikant (p>0,05). Eine Hypophosphatamie fand sich nur bei 63% der Kinder. Dagegen waren ein sekundarer Hyperparathyreoidismus bei allen und eine erhohte Aktivitat der alkalischen Phosphatase bei 107 der 115 Kinder nachweisbar. Die Serumspiegel von 25-Hydroxyvitamin D (25-OHD) waren bei 109 Kindern erniedrigt und bei 6 der 115 Kinder normal. Die bei 24 Patienten gemessenen 1,25-Dihydroxyvitamin-D-Spiegel [1,25-(OH)2D-Spiegel] waren normal oder erhoht. Parathormon war positiv zur Urin-cAMP-Ausscheidung korreliert (p

The high prevalence of vitamin D deficiency in relation to diabetes mellitus is well reported in the literature. However, type I diabetes mellitus (T1DM) in association with resistant rickets is extremely rare and reported in only one previous case. The authors describe here a case of type II vitamin D-dependent rickets (VDDR type II) in a 10-year-old Indian girl who presented with diabetic ketoacidosis (DKA). DKA as a presenting manifestation of T1DM in a patient with VDDR type II has never been reported before in worldwide literature.

Vitamin D-dependent type two rickets (VDDRII) is a rare autosomal recessive disorder caused by mutation in the vitamin D receptor gene, leading to end-organ resistance to 1,25(OH) 2 vitamin D3. It presents with refractory rickets and growth retardation presenting in the first year of life. It is frequently associated with alopecia totalis. Due to target organ resistance, its response to vitamin D is poor. The recommended treatment is giving supraphysiological dose of 1,25(OH) 2 vitamin D3 and a high dose of oral or intravenous calcium. The response of alopecia to treatment is generally poor. We present a 3-year-old male child with VDDRII whose alopecia and rickets partially responded to 1,25(OH) 2 vitamin D3.

This report describes the presenting signs, biochemical abnormalities, and radiographic changes in a 4-month-old kitten with vitamin D-dependent rickets type 2. Details of therapy are described and possible reasons for treatment failure are discussed.

Vitamin-D-dependent rickets type 2 results from autosomal recessive mutations of the vitamin D receptor gene. With congenital total body alopecia and onset of rickets during the second half of the first year of life, patients display rapidly progressing rachitic bone changes, hypocalcemia and secondary hyperparathyroidism. This article describes extensive personal experience with about one third of the world’s reported cases, their clinical course, the physiological consequences, diagnostic steps, molecular findings and therapeutic approach, as they developed over the course of the last 25 years.

Mucopolysaccharidosis I is a metabolic disease of autosomal recessive inheritance caused by deficient activity of α-L-iduronidase. The clinical phenotype presents a wide spectrum of signs in the first year of life. We report a child with clinical features and laboratory data consistent with mucopolysaccharidosis I who precociously developed hydrocephalus and flexion spasms with hypsarrythmia in the electroencephalographic registration characteristic of West's syndrome. His radiologic and biochemical data suggested vitamin D-dependent rickets. To our knowledge, this is the first report of a patient demonstrating an association among mucopolysaccharidosis I, West's syndrome, and vitamin D-dependent rickets. (J Child Neurol 2002;17:149-151).

Ultrapremature babies accompanied by intrauterine growth retardation may require supplemental calcium and phosphorus far above the recommended doses.

Sri Lanka Journal of Child Health , 2006; 35: 148-50 Key words: Vitamin D dependent rickets, identical twins DOI = 10.4038/sljch.v35i4.37

A patient with vitamin D dependent rickets with decreased sensitivity to 1,25-Dihydroxyvitamin D was observed. She suffered from bone pain of two years duration beginning at 12 years of age and was found to be suffering from hypocalcemia, secondary hyperparathyroidism and osteomalacia. Laboratory findings revealed normal serum 25-hydroxyvitamin D (27 ng/ml) and markedly elevated serum 1,25-dihydroxy-vitamin D (131.9 pg/ml). The hypocalcemia was refractory in spite of administration of 25,000 units of vitamin D2, but therapy with high doses of oral la-hydroxyvitamin D3 resulted in significant elevation of the serum calcium level. The clinical findings and course of the patient's disease were quite different from those of other patients with vitamin D dependent rickets reported by other authors.

Rickets diagnosed in a 12-week-old female St Bernard was attributed to an inborn error in vitamin D metabolism. Radiographically the physes were enlarged radially and axially, and metaphyseal bone adjacent to the physes was widened and cup-shaped. Serum biochemical abnormalities were hypocalcaemia, hypomagnesaemia, and hyperparathyroidism. Treatment was given with dihydrotachysterol, a synthetic sterol that is metabolised to a pharmacologically active analogue of 1,25 dihydroxycholecalciferol by the liver. This resolved the rachitic skeletal lesions completely in six weeks, as assessed radiographically, and maintained the serum calcium at the lower end of the normal range.

Vitamin D-dependent rickets Type II is a rare autosomal recessive disorder. Alopecia of the scalp or the body is seen in some families with Vitamin D-dependent rickets Type II. We report a child with this disease, and review the salient features of this disease with emphasis on the associated alopecia. Due to lack of facilities for estimation of 1, 25(OH)2 D and parathyroid hormone, alopecia remains the only clue to the diagnosis of this rare syndrome in association with resistant rickets. Key words: Rickets, Vitamin D metabolism DOI: 10.3126/jnps.v30i1.2460 Journal of Nepal Paediatric Society Vol.30(1) 2010 46-49

An 8 1/2-year-old girl presented with rickets. This had developed despite a normal diet and in the absence of symptoms, signs, or laboratory evidence of malabsorption, hepatic or renal disease. The rickets healed with physiological doses of 1-alpha-hydroxy-cholecalciferol. It is suggested that this case provides evidence for genetic and metabolic heterogeneity in vitamin D-dependent rickets.

A 12-yr-old female patient with an unusual form of vitamin D dependency and alopecia is described. She was a product of consanguineous mating and developed signs and symptoms suggesting vitamin D dependency early in life. Neither 150 microgram/day (6 microgram/kg.day) 1 alpha-hydroxyvitamin D3 nor 5 microgram/day (0.2 microgram/kg.day) 1,25-dihydroxyvitamin D3 proved to have an effect on her abnormal serum chemistry. Seven million international units per day (about 2 x 10(5) IU/kg.day) of native vitamin D restored her serum chemistry to normal and brought about marked improvement on skeletal radiographs, when her serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and 24,25-di-hydroxyvitamin D were 4250, 4.8, and 35 ng/ml, respectively. Even with the high serum levels of vitamin D metabolites, her intestinal 47Ca absorption rate remained in the lower normal range and urinary calcium excretion was decidedly low. Association of hypoparathyroidism was ruled out. These results suggest that the patient has extreme and-organ (intestine) hyposensitivity, probably of congenital origin, to the biologically active metabolites of vitamin D.

Requirements of vitamin D2, vitamin D3, 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3 were studied in five patients with vitamin-D-dependent rickets, a recessively inherited form of v...