1. Nutritional Rickets In Infancy And Childhood Re-Emergence Of A Preventable Problem Arlette Soros, MD, Jayashree Rao, MD, Ricardo Gómez, MD, Stuart A. Chalew, MD, and Alfonso Vargas, MD Department of Pediatrics, Division of Endocrinology Louisiana State University Health Sciences Center and Children’s Hospital – New Orleans

2. Nutritional Vitamin D Deficiency Increase in prevalence in the USA and other developed countries. Vitamin D is required for calcium absorption and promotes normal bone mineralization, being its mayor function to maintain calcium and phosphorus levels within the normal range. ↓ vitamin D → ↓calcium absorption → ↓serum ionized calcium level → stimulates PTH → mobilizes calcium and phosphorus from the bone to restore serum calcium levels.

3. Holick M: Journal of Clinical Investigation, 2006, 116:2062-72

4. Holick M: Journal of Clinical Investigation, 2006, 116:2062-72

7. Characteristics Serum 25(OH)-vitamin D: <20 ng/mL Peak age: between 3 and 18 months Dark skinned mothers Maternal nutritional vitamin D deficiency Chelating natural or pharmaceutical agents Malabsorption syndromes Congenital or perinatal liver disease

8. Description of Clinical Cases Four patients between 0.3 and 3.3 years of age presented to our clinics with –Tetany, carpo-pedal spasms, and/or seizure –Bony deformities (bowed legs, widening of wrists and ankles, “rachitic rosary”) All breastfed without vitamin D supplementation After weaning from breast milk had negligible intake of vitamin D fortified milk or dairy products. Very limited exposure to solar UVB radiation.

9. Table 1a. PatientAge (yrs) Ethnic Group Total Ca Ionized Ca 2+ P 10.3Arabic6.12.66.1 23.3AA6.94.3 32.8AA6.32.24.4 41.5AA7.04.35.0 Normal8.7-10.3 mg/dL 4.3-5.9 mg/dl 4.0-9.5 mg/dL

10. Table 1b. Mg Alkaline Phosphatase PTH25(OH)- vitamin D 1,25(OH) 2 - vitamin D 1.76942521195 1.91158448.1133.9 2.011274545.9186 1.53911565.093 1.7-2.2 mg/dL 70-250 U/L 10-60 pg/mL 20-60 ng/mL 15-90 pg/mL

11. Description and Progress Renal and liver functions were normal. All had complete or near complete resolution of their medical problems with appropriate therapeutic doses of intravenous and then oral calcium plus oral ergocalciferol or calcitriol.

12. Risk Factors (1) Duration of breast feeding without vitamin D supplementation. Maternal vitamin D deficiency. High phytic acid dietary content. Vegetarian diet and/or poor dietary intake of dairy products. Dark skin pigmentation.

13. Risk Factors (2) Seasonal: Increased incidence from late fall to early spring Living at latitudes >35° Environmental factors: air pollution, cloud cover, ozone layer

14. Signs and Symptoms (1) Bony deformities –Bowing of the legs (genu-varum, tibiae vara) –Knock-knees (genu-valgum) –“Rachitic rosary” costochondral junctions –Swelling of the epiphysial growth plates –Frontal bossing of the skull Pathological fractures. Poor growth Delayed dentition

15. Signs and Symptoms (2) Slow motor development. Muscle weakness. Extra skeletal –Tetany –Seizures –Laryngospasm –Hypocalcemic myocardiopathy –Death.

16. Biochemical Indicators Serum 25(OH)-vitamin D: <20 ng/mL. Seasonal fluctuation. Serum 1,25(OH) 2 -vitamin D: low, normal, or elevated; but not enough to compensate Serum PTH: normal or elevated Serum Ca: low Serum P (HPO 4 = ): low Serum Mg: normal Serum Alkaline phosphatase: elevated

17. Treatment (1) Vitamin D 2 (ergocalciferol) Vitamin D 3 (cholecalciferol) 200,000 – 600,000 IU orally with adequate dietary calcium. –2,000–4,000 IU daily for 3 – 6 months. –Single therapy

18. Treatment (2) Vitamin D: 100,000 IU every 3 – 4 months maintains serum 25(OH)-vitamin D concentration within normal range. Subcutaneous or intramuscular in children with malabsorption. Calcium supplementation by IV infusion if tetany or seizure are the presenting symptoms. Adequate oral calcium intake

19. Prevention (1) Vitamin D 400 IU daily and adequate calcium intake: –Breastfed infant supplement with 400 IU vitamin D –Infant taking <500 mL/day of vitamin D fortified milk/formula supplement 400 IU Infant’s with low serum 25(OH)-vitamin D may need >400 – 1,000 IU of vitamin D/day Adequate sunlight exposure.

20. Prevention (2) All formula sold in the USA contains at least 400 IU/L vitamin D. If daily intake is >500ml but <1000ml of fortified milk or formula add 200 IU of vitamin D.

21. Vitamin D Deficiency - Long Term Effects. Osteoporosis in later life. Cancer of the colon, prostate, breast, ovary, esophagus, etc. Autoimmune diseases like type 1 Diabetes Mellitus, Crohn’s disease. Hypertension and heart diseases.

22. Bibliography (1) Holick, Michael: Resurrection of Vitamin D Deficiency and Rickets. J Clin Invest 116:2062-72, 2006 American Academy of Pediatrics, Gartner LM, Greer FR, Section on Breastfeeding and Committee on Nutrition. Prevention of rickets and vitamin D deficiency: New guidelines for vitamin D intake. Pediatrics 111:908-910, 2003 DeLucia MC, Mitnick ME, Carpenter TO. Nutritional rickets with normal circulating 25- hydroxy vitamin D: a call for reexamining the role of dietary calcium intake in North American infants. J Clin Endocrinol Metab 88:3539-3545, 2003

23. Bibliography (2) Ashraf M, Mick J, Atchison J, Petrey B, Abdullatif H and McCormick K: Prevalence of hypovitaminosis D in early infantile hypocalcemia. J Pediatr Endocrinol & Metabol 19:1025, 2006 Finberg L: Vitamin D deficiency and rickets. J Pediatr Endocrinol & Metabol 19:203, 2006 McAllister JC, Lane AT and Buckingham BA: Vitamin D deficiency in the San Francisco Bay area. J Pediatr Endocrinol & Metab 19:205, 2006 Shaikh U and Alpert PT: Nutritional rickets in Las Vegas, Nevada. J Pediatr Endocrinol & Metabol 19:209, 2006

24. Bibliography (3) Shetty AK, Thomas T, Rao J, Vargas A: Rickets and secondary craniosynostosis associated with long-term antacid use in an infant. Arch Pediatr Adolesc Med 152:1243-1245, 1998 Chesney RW: EDITORIAL - A new form of rickets during infancy: Phosphate depletion-induced osteopenia due to antacid ingestion. Arch Pediatr Adolesc Med 152:1168-1169, 1998