RICKETS By- shahbaz ahmed

Definition Rickets is a disease of growing bone that is caused by unmineralized matrix at the growth plates and occurs in children only before fusion of epiphysis.

ETIOLOGY Vitamin D disorders. Calcium deficiency. Phosphorus deficiency. Renal losses.

Vitamin D disorders Nutritional vitamin D deficiency. Congenital vitamin D deficiency. Secondary vitamin D deficiency. Malabsorption Increased degradation. VDDR type 1 VDDR type 2 Chronic kidney disease.

CALCIUM DEFICIENCY Low intake Diet Premature infants Malabsorption Primary disease Dietary inhibitors of calcium absorption.

PHOSPHORUS DEFICIENCY Inadequate intake. Premature infants. Aluminum containing antacids.

RENAL LOSSES Distal renal tubular acidosis. X-linked hypophosphatemic rickets. Autosomal dominant hypophosphatemic rickets. Hereditary hypophosphatemic rickets with hypercalciuria. Overproduction of FGF-23. Fanconi syndrome. Dent disease. Distal renal tubular acidosis.

Clinical features

RADIOLOGY-FIRST LEVEL INVESTIGATION PA radiographs of wrists, knee and chest. FRAYING The edge of metaphysis loses its sharp border. CUPPING The edge of metaphysis changes from convex to flat or concave surface. Seen at distal end of radius, ulna and fibula.

SECOND LEVEL INVESTIGATIONS Blood urea, creatinine, electrolytes, ABG Tubular reabsorption of phosphate (Trp) Urine analysis for specific gravity, glucose, protein, amino acids, potassium and calcium. USG abdomen LFT, malabsorption.

LAB FINDINGS IN DISORDERS CAUSING RICKETS N-NORMAL D-DECREASED I-INCREASED RD-RELATIVELY DECREASED Ca-CALCIUM Pi-INORGANIC PHOSPHORUS PTH-PARATHORMONE ALP-ALKALINE PHOSPHATASE

Treatment of rickets is based on etiology.

NUTRITIONAL VITAMIN D DEFICIENCY Etiology combination of poor intake and cutaneous synthesis. Clinically typical presentation with symptoms of hypocalcemia, prolonged laryngospasm.

Treatment stoss therapy-300000-600000 IU orally/IM as 2-4 doses/day OR 2000-4000 IU/day for 4-6wks for hypocalcemic- intravenous calcium acutely followed by oral calcium supplements

Congenital vitamin d deficiency Occurs when there is severe maternal vit D deficiency. Newborns have symptomatic hypocalcemia, IUGR, decreased bone ossification, classical rachitic changes. Vit D supplementation and adequate intake of calcium and phosphorus. Prenatal vitamins.

Secondary vitamin d deficiency Inadequate absorption , decreased hydroxylation, inadequate intake can leads to deficiency. GI and liver diseases Defects in bile acid metabolism Celiac disease Crohn disease Treatment Vit D supplements, 25-D(25-50mcg/day), 1,25-D

Vit d dependent rickets type1 An autosomal recessive disorder, have mutations in the gene encoding renal 1 α - hydroxylase, preventing conversion of 25-D into 1,25-D. Classic features of rickets.

Treatment These patients respond to long-term treatment with 1,25-D (calcitriol). Initial doses are 0.25-2 μ g/day, and lower doses are used once the rickets has healed. Periodic assessment of urinary excretion of calcium of < 4 mg/kg/day to avoiid nephrocalcinosis

Vit d dependent rickets type 2 Mutations in the gene encoding the vitamin D receptor. Presents mostly in infancy with features of rickets. Approximately 50-70% of children have alopecia, which tends to be associated with a more severe form of the disease and can range from alopecia areata to alopecia totalis.

Treatment extremely high doses of vitamin D 2 , 25-D or 1,25-D, especially patients without alopecia. Calcium (1000-3000mg/day) Treatment of patients who do not respond to vitamin D is difficult.

Calcium deficiency Seen in babies who started weaning with calcium level of < 200 mg/day. Intravenous nutrition without calcium. Malabsorption-celiac disease, intestinal betalipoprotienemia, small bowel resection. Classic signs and symptoms of rickets. Increased levels of alkaline phosphatase, PTH, and 1,25-D. Treatment providing adequate calcium, typically as a dietary supplement (doses of 700 [1-3 yr age], 1,000 [4-8 yr age], 1,300 [9-18 yr age] mg/day of elemental calcium are effective).

PHOSPHOROUS DEFICIENCY Decreased phosphorus absorption can occur in diseases associated with malabsorption(celiac disease, cystic fibrosis, cholestatic liver disease), but if rickets develops, the primary problem is usually malabsorption of vitamin D and/or calcium. Aluminum-containing antacids. Phosphatonin -Phosphatonin is a humoral mediator that decreases renal tubular reabsorption of phosphate and therefore decreases serum phosphorus.

X-Linked Hypophosphatemic Rickets Autosomal Dominant Hypophosphatemic Rickets Autosomal Recessive Hypophosphatemic Rickets Hereditary Hypophosphatemic Rickets with Hypercalciuria Overproduction of Phosphatonin

Fanconi syndrome Generalized dysfunction of the renal proximal tubule. There are renal losses of phosphate, amino acids, bicarbonate, glucose, urate, and other molecules that are normally reabsorbed in the proximal tubule. Presents mainly as hypophosphatemia and proximal renal tubular acidosis. Hypophosphatemia leads to rickets. Failure to thrive is a complication

Dent Disease X-linked disorder. Mutations in gene encoding chloride channels. Affected males have variable manifestations, including hematuria, nephrolithiasis, nephrocalcinosis, rickets, and chronic renal failure. Treatment Oral phosphorus supplements 1,25-D

RICKETS OF PREMATURITY Seen in very low birth weight infants. Pathogenesis- 80% transfer of calcium and phosphorus takes place in 3rd trimester, fails in this.. Rickets occurs because unsupplemented breast milk and standard infant formula do not contain enough calcium and phosphorus to supply the needs of the premature infant.

Clinical manifestations- Nontraumatic fractures Clinical manifestations- Nontraumatic fractures. Respiratory distress develops more than 5 wks after birth of premature infant. Classical rachitic findings

Laboratory findings- Radiological changes Serum phosphorus –low or low-normal Low urine phosphate Trp >95% 1,25-D –high or high-normal Elevated serum calcium levels. Alkaline phosphate levels elevated.

Prevention Provision of adequate amount of calcium, phosphorus, Vit D Increased mineral feeding of infant till weight becomes 3-3.5kg. Treatment Adequate delivery of calcium, phosphorus and Vit D

Distal renal tubular acidosis Failure to thrive Metabolic acidosis Hypercalciuria Nephrocalcinosis Treatment Alkali therapy