1. بسم الله الرحمن الرحيم

2. RICKETS ( الكساح ) “Defective mineralization of the bone growth plate (the metaphysis)”. HISTORY It has been known since Romans & in the 16 th century it was classically described by Whistler & Glisson.

3. BASIC SCIENCE BACKGROUNDS Bone formation is a complex process integrated by hormonal & growth factors (matrix + mineralization). At metaphysis: growth is by mineralization of osteoid tissue & is dependent on adequate calcium (Ca 2+ ), phosphorus (P) & other elements levels (as magnesium, copper & fluorine). At epiphysis & diaphysis: growth is by balance between bone resorption* & re-formation (remodeling) regulated by vitamin D, parathyroid hormone* (PTH), growth hormone (through IGFs), thyroid hormones, insulin, glucocorticoids* & sex hormones (pubertal).

4. * Ca 2+ & P homeostasis: Vitamin D (UV irradiation + Dietary), activated by liver (25 OH-Vit.D) then by kidney (1,25[OH] 2 -Vit.D) by Ca 2+ or P in plasma. PTH ( Ca 2+ ) Intestinal Ca 2+ &P absorption Bone resorption & serum Ca 2+ Distal tubular reabsorption of Ca 2+ serum Ca 2+ Activate 1-hydroxylase 1,25[OH] 2 -Vit.D Renal acid excretion & tubular reabsorption of ( PTH): -P phosphaturia & hypopohsphatemia -Aminoacids generalized aminoaciduria

5. PATHOGENISIS Deficiency of Ca 2+ &/or P in plasma chondrocyte mineralization at the mataphysis (other elements role?). plasma Ca 2+ PTH bone resorption & return of plasma Ca 2+ to N + hyperphosphaturia & plasma P. osteoblastic activity alkaline phosphatase (ALP). Metaphyseal growth slows & bone age is retarded. Trabecular bone demineralization a greater proportion of unmineralized osteoid (osteomalacia). Epiphyseal line is irregular & frayed + new uncalcified osteoid = rachitic metaphysis +/- cortical bone fractures.

6. ETIOLOGY Calciopenic(2 ry -PTH): - vit. D effects ( defects in diet, UV, maternal, hepatic or renal activation, drugs or its action). - Malabsorption ( fatty acids, phytates or Ca 2+ / P). Phosphopenic: - Renal (1 ry isolated, hereditary or acquired Fanconi’ syndrome, prox. renal tubular acidosis or oncogenic). - P deficiency or malabsorption. Combined: - Preterm metabolic bone disease (placento intestinal).

7. PRESENTATION Clinical picture depends on age & associated disease. * Age: -Congenital: usually none but with severe maternal osteomalacia neonatal tetany & enamel defects. -Infantile( 4mo), wide epiphysis (wrists, ankles & costochonderal), boxy & asymmetrical head, delayed teeth eruption, hypotonia (lax abdomen & joints), delayed sitting, wide anterior fontanel, bow-legs, pigeon chest & Harrison groove. -Toddler:+short, not walking or delayed with deformities. -Adolescent: Coxa vara, genu valgum, waddling & pain.

8. -Nutritional: protein-calori malnutrition(weight,mid-arm, s.c.fat, oedema or vit.def.) but if severe, rickets is mild. -Renal: polyuria, acidosis, growth failure or eye signs. -Hepatic: jaundice, steatorrhea or cirrhosis. -Drugs: epilepsy. -Malabsorption: ch. diarrhea, growth failure or vit.def. -Vit. D resistance: alopecia or other siblings. -1 ry hypopohsphatemia : affected sisters or mother (XD). -Preterm: minerals or vit. def. PRESENTATION (Cont’d) *Associated disease:

14. COMPLICATIONS Deformities: mild trauma fractures (greenstick) & pelvic in girls difficult labor. Infection: respiratory. Tetany(-Ca 2+ ): -Latent +ve Chvostek, Trousseau & peroneal signs. -Manifest carpopedal spasms, stridor or generalized convulsions but in neonates cyanosis or apnea. Associated disease: tubular disorder dehydration & malabsorption malnutrition.

15. INVESTIGATIONS Chemistery: - s.ALP, but age interpreted (higher in growth periods). - s.P(phosphopenic or 2 ry PTH), except in renal failure. -N. s.Ca 2+ or low when PTH exhaustion occurs. - s.25 OH-Vit. D in vit. D deficiency & hepatic disease. - s.1,25[OH] 2 Vit.D in renal failure & if s.25OH-Vit.D. - Aminoaciduria in renal tubular disease & 2 ry PTH. -Glucosuria & aminoaciduria in Fanconi’ syndrome. X-ray: mineralization, epiphyseal growth & cupping, fraying & splaying of mataphysis+/-deformity, fracture.

25. DEFFERNTIAL DIAGNOSIS Cause of rickets(see above & by response to treatment). Metaphyseal dysplasia by N. chemistry & no fraying. Hypophosphatasia by s.ALP & loss of teeth. Congenital deformities by N. chemistry & x-ray. Vit. D deficiency by 1-6x10 3 u. for 4-6 wk then lower dose judged by response till healing then 400u./d maint. 6x10 5 u. i.m. vit. D (single) for ignorant parents & DD. Cause treatment, if possible. Prophylaxis for preterm & maternal osteomalacia baby. TREATMENT

31. REFERENCES 1. Forfar and Arneil’s textbook of paediatrics (1998). Campbell AGM & Macintosh N (eds.), 5 th edition, Churchil Livingstone, UK; pp: 301-4, 331, 1057-8, 1194-6, 1866. 2. Nelson textbook of pediatrics (2000). Behrman RE, Kliegman RM & Jenson HB (eds.), 16 th edition, Saunders, USA; pp: 184-7, 1169, 1207, 1600, 1610-1, 1829, 2133-8. THANK YOU