بسم الله الرحمن الرحيم. RICKETS ( الكساح ) “Defective mineralization of...

الله بسمالرحيم الرحمن

RICKETS (الكساح)

“Defective mineralization of the bone growth plate (the metaphysis)”.

HISTORY It has been known since Romans & in the 16th century it was classically described by Whistler & Glisson.

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 (Ca2+), 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).

* Ca2+ & P homeostasis:

Vitamin D (UV irradiation + Dietary), activated by liver (25 OH-Vit.D) then by kidney (1,25[OH]2-Vit.D) by Ca2+or P

in plasma.

PTH ( Ca2+)

Intestinal Ca2+&P absorption

Bone resorption & serum Ca2+

Distal tubular reabsorption of Ca2+ serum Ca2+ Activate 1-hydroxylase 1,25[OH]2-Vit.D Renal acid excretion & tubular reabsorption of ( PTH):

-P phosphaturia & hypopohsphatemia-Aminoacids generalized aminoaciduria

PATHOGENISISDeficiency of Ca2+ &/or P in plasma chondrocyte mineralization at the mataphysis (other elements role?).

plasma Ca2+ PTH bone resorption & return of plasma Ca2+ 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.

ETIOLOGY

Calciopenic(2ry-PTH): - vit. D effects ( defects in diet, UV, maternal, hepatic or renal activation, drugs or its action). - Malabsorption ( fatty acids, phytates or Ca2+/ P).

Phosphopenic: - Renal (1ry isolated, hereditary or acquired Fanconi’ syndrome, prox. renal tubular acidosis or oncogenic). - P deficiency or malabsorption.

Combined: - Preterm metabolic bone disease (placento intestinal).

PRESENTATIONClinical picture depends on age & associated disease. *Age: -Congenital: usually none but with severe maternal osteomalacia neonatal tetany & enamel defects. -Infantile(< 1yr, +/- preterm): craniotebes (> 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.

-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.

-1ry hypopohsphatemia : affected sisters or mother (XD).

-Preterm: minerals or vit. def.

PRESENTATION (Cont’d)*Associated disease:

COMPLICATIONSDeformities: mild trauma fractures (greenstick) & pelvic in girls difficult labor.

Infection: respiratory.

Tetany(-Ca2+): -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.

INVESTIGATIONSChemistery: - s.ALP, but age interpreted (higher in growth periods). - s.P(phosphopenic or 2ry PTH), except in renal failure. -N. s.Ca2+ or low when PTH exhaustion occurs. - s.25 OH-Vit. D in vit. D deficiency & hepatic disease. - s.1,25[OH]2Vit.D

in renal failure & if s.25OH-Vit.D . -Aminoaciduria in renal tubular disease & 2ry PTH. -Glucosuria & aminoaciduria in Fanconi’ syndrome.

X-ray: mineralization, epiphyseal growth & cupping, fraying & splaying of mataphysis+/-deformity, fracture.

DEFFERNTIAL DIAGNOSISCause 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 1-6x103u. for 4-6 wk then lower dose judged by response till healing then 400u./d maint.

6x105u. i.m. vit. D (single) for ignorant parents & DD.

Cause treatment, if possible.

Prophylaxis for preterm & maternal osteomalacia baby.

TREATMENT

REFERENCES1. Forfar and Arneil’s textbook of paediatrics (1998). Campbell AGM & Macintosh N (eds.), 5th 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.), 16th edition, Saunders, USA; pp: 184-7, 1169, 1207, 1600, 1610-1, 1829, 2133-8.

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