1. Rickets

2. Objectives Definition Epidemiology Pathophysiology Presentation Role of vitamin D Etiology Management Summary

3. Definition a disease of growing bone, occurs in children before fusion of the epiphyses, due to unmineralized matrix at the growth plates, resulting in growth retardation and delayed skeletal development

4. epidemiology In developed countries, rickets is a rare disease incidence of less than 1 in 200,000 In saudiarabia[1] retrospective study at King Abdulaziz Medical City-King Fahad National Guard Hospital in Riyadh, Saudi Arabia 2009 196 infants (70%) were exclusively on breast-feeding (127 males, 69 females) with no supplementation The records of Saudi infants and children under the age of 14 months over a 10-year period (between January 1990 and January 2000) were reviewed. 283 infants were studied. Epidemiology of nutritional rickets in children. Al-Atawi MS, Al-Alwan IA, Al-Mutair AN, Tamim HM, Al-Jurayyan NA. Department of Pediatric, National Guard Health Affairs, King Abdulaziz Medical City, Riyadh, Saudi Arabia

5. Epidemiology Higher risk for developing rickets include: Children ages 6 months to 24 months are at highest risk, because of rapidly growing bones Breast-fed infants whose mothers are not exposed to sunlight Breast-fed infants who are not exposed to sunlight Premature Babies dark skin Babies Individuals consuming some medications: Anticonvulsants, Cadmium, Fluoride, Lead, Aluminum

6. Pathophysiology Bone consists of a protein matrix called osteoidand a minerals, principally composed of calcium and phosphate, mostly in the form of hydroxyapatite. Because growth plate cartilage and osteoid continue to expand, but mineralization is inadequate, the growth plate thickens. There is also an increase in the circumference of the growth plate and the metaphysis.

8. Listlessness

9. Protuding abdomen

10. Muscle weakness (especially proximal)

12. Frontal bossing

13. Delayed fontanelle closure

14. Delayed dentition; caries

17. Valgus or varus deformities

18. Bowed legs (genuvarum) in Toddlers

19. Knock-knees(genuvalgum) in older children

20. Anterior bowing of the tibia and femur

21. Coxavara

23. Seizures

25. Vitamin D It is important for calcium homeostasis and for optimal skeletal health. vitamin D3 Cholecalciferol made in the skin or obtained in the diet from fatty fish Vitamin D2 ergocalciferolalciferol Obtained from plants CALCITRIOLE Active Form

27. Vitamin D actions Promotes Ca & P absorption in small gut . Increase Ca & P reabsorption in the kidneys. Direct effect of menirals metabolism of bones "depositioin & resorption "

31. Vitamin D–dependent rickets “type I” a.k.a vitamin D pseudodeficiency (PDDR) because it can be corrected with high daily doses of vitamin D Genetic deficiency disorder, have mutations in the gene encoding renal 1α-hydroxylase Autosomal recessive inheritance, chromosome 12 They have normal levels of 25-D, but low levels of 1,25-D ( LOW calcitriol), high PTH and low serum phosphorus levels. Treatment is calcitriol 0.5-1.5 mcg/d. Also respond to pharmacologic doses of vitamin D (5000-10,000 u/d).

32. Vitamin D–resistant rickets “type II” a.k.a hereditary 1,25-dihydroxyvitamin D–resistant rickets [HVDRR] autosomal recessive inheritance of a mutations in the gene encoding the vitamin D receptor The clinical picture is evident early in life, and consists of rickets with very severe hypocalcemia and alopecia Hypocalcemic and usually normophosphatemic. Some patients have benefited from intravenous calcium (400-1400 mg/m2/d) followed by oral therapy with high doses of calcium

33. Defective 25-hydroxylase Two cases of have been reported, one in US and the other Germany. autosomal recessive Inheritance . The clinical picture resembles that observed in nutritional rickets, with a later age of onset. Treatment with calcidiol in physiologic amounts

34. Familial hypophosphatemia X-linked “PHEX” (PHosphate-regulating gene with homology to Endopeptidases on the X chromosome) & autosomal recessive “DMP1”inheretance kidneys fail to reabsorb sufficient phosphate, leading to low levels of serum P This is usually evident only after age 6-10 months, Prior to this, the glomerular filtration rate is low, which sustains an adequate phosphate level.

35. Familial hypophosphatemia Clinical findings are similar to those of nutritional rickets, but without proximal myopathy. Patients respond well to a combination of oral phosphorus and 1,25-D (calcitriol), 1-3 g of elemental phosphate per day in 5 divided doses + Calcitrol is administered 30–70 ng/kg/day divided into 2 doses

36. Drug-induced rickets Chronic anticonvulsant therapymay cause rickets, regardless of appropriate vitamin D intake. The main mechanism is related to induction of hepatic cytochrome P-450 hydroxylation so generating inactive metabolites

37. Fanconi syndrome is a disorder of proximal renal tubular transport  loss of phosphate, amino acids, glucose, bicarbonate, and uric acid wasting . A potential drug-induced Fanconi syndrome has been noticed in children treated with ifosfamide, a derivative of cyclophosphamide.

38. Renal osteodystrophy

39. Lab works Blood tests: CA P ALP Serum 25(OH)D (is the best test to determine vitamin D status) < 32 ng/mL is considered vitamin D insufficient Metabolic acidosis PTH ( 2nd hyperparathyroidism)

41. skull changes "square headed" or Craniotabes, Frontal and parietal bossing, flat occiput appearance.

43. The best single radiographic view for infants and children younger than 3 years is an anterior view of the knee that reveals the metaphyseal end and epiphysis of the femur and tibia. Shows Widening and cupping and fraying of the metaphyseal regions

44. Bow legs

45. Knock-knees

46. Recommended daily intake of calcium is as follows: 1 to 3 years of age. 500 mg 4 to 8 years of age. 800 mg 9 to 18 years of age. 1,300 mg