Vitamin d resistant rickets

rickets

1. Vit -D resistant rickets By P.Padma Priyanka

2. Calcium deficiency Sec. to inadequate dietary calcium Weaning early from breast milk/formula <200mg/day Low intake/malabsorption IV nutrition

3. Clinical features Classical signs of rickets Infancy or early childhood Lab -  ALK,PTH,1,25-D s.ca -normal/low low urine ca ,serum phosphorus(aminoaciduria) co-existing vit D def Treatment - 700(1-3y) 1000(4-8y) 1300 (9-18y)mg/day

4. Phosphorus deficiency Inadequate intake Isolated malabsorption- aluminium containing antacids Discontinue antacid and short-term phosphorus supplementation

5. Rickets of prematurity Very low birthweight infants(<1000g) and younger gestational age Transfer of calcium and phosphorus 80% occurs in 3 rd trimester Unsupplemeted breastmilk and standard infant formula do not contain enough calcium and phosphorus Risks factors- cholestatic jaundice,parentral nutrition,diuretics and corticosteroids 1-4 months after birth

6. Clinical features Non-traumatic fractures- legs,arms,ribs Respiratory distress and poor ventilation(>5weeks) Negative effects on growth-beyond 1yr Enamel hypoplasia Dolicocephaly Frontal bossing,rachitic rosary,craniotabes,widened wrists and ankles

7. Laboratory findings Low serum phosphorus Low urine phosphate level(reabsorption is >95%) Normal 25-D High 1,25-D  demineralization Serum calcium low,normal,high and hypercalciuria Increaed ALP

8. No single blood test is 100% sensitive for diagnosis of rickets ALP >5-6 times upper limit of normal level for adults phosphorus<5.6mg/ dL Confirmed by radiological evidence of wrists and anklesarms and legs-may reveal fractures Rachitic rosary may be seen in x-ray (but changes are not evident until there is >20-30% reduction in bone mineral content)

9. Diagnosis Screening tests-weekly measuremen tof calcium,phosphorus and ALP Serum HCO 3 - as metabolic acidosis causes bone dissolution Atleast 1 screening x-ray at 6-8weeks

10. Prevention Calcium,phosphorus,vit D parenterally Current aminoacid preparations Early transition to enteral feeds Fortified human milk or preterm infant formula Avoid soy formula Increased mineral feeds till baby reaches 3-3.5kg Vit –D 400IU/day

11. X-linked hypophosphatemic rickets Most common genetic disorder causing rickets due to hypophosphatemia Prevalance of 1/20,000 On Xp22 Female carriers are affected X-linked dominant disorder

12. Pathophysiology Defective gene- PHEX gene Ph osphate-regulating gene with homology to E ndopeptidases on the X -chromosome Indirect role in inactivating the phosphatonin ( humoral mediator) FGF-23 Mutations in PHEX  increased levels of FGF-23

13. Clinical manifestations Rickets Abnormalities of lower extremities and poor growth Delayed dentition Tooth abscesses Hypophosphatemia and short stature without clinically evident bone disease

14. Laboratory findings

15. Treatment Respond well to PHOSPHORUS & CALCITRIOL Phosphorus - daily requirement 1-3g elemental phosphorus in 4-5 divided doses Frequent dosing-2 advantages Calcitriol – 30-70mg/kg/day in 2 divided doses Short stature-GH Several deformities-osteotomies only when Rx led to resolution of bone disease

16. Complications of treatment Occurs when there is not adequate balance

17. Monitoring Laboratory monitoring of Serum calcium Phosphorus ALP PTH Urinary calcium Periodic renal ultrasounds

18. Prognosis Response to therapy is usually good Girls<boys (probably due to X-linked) Short stature may persist despite healing of rickets

19. Autosomal dominant hypophosphatemic rickets

20. Autosomal resistant hypophosphatemic rickets

21. Hereditary hypophosphatemic rickets with hypercalciuria

22. Rachitic leg abnormalities Muscle weakness Bone pain Short stature Disproportionate decreased length of lower extremities Nephrolithiasis sec. to hypercalciuria

23. Lab- hypophosphatemia,renal phospahte wasting,increased serum ALP,increased 1,25-D,low PTH levels Treatment – oral phosphorus 1-2.5g/day of elemental phosphorus in 5 divided doses This decreases serum 1,25-D and corrects hypercalciuria Response- excellent with resolution of pain,weakness,radiographic evidence of rickets

24. Overproduction of phosphatonin Tumor-induced osteomalacia (adults>children) M cCune-Albright syndrome-triad of polyostotic fibrous dysplasia,hyperpigmented macules,polyendocrinopathy ) Epidermal nevus syndrome Neurofibromatosis

25. Fanconi syndrome Sec. to generalized dysfunction of the renal proxinal tubule Loss of phosphate,AA,HCO 3 - ,glucose,urate etc. Some-partial dysfunction Hypophosphatemia,renal tubular acidosis Rickets+bone dissolution  FTT

26. Dent disease X-linked disorder Mutation in gene coding for chloride channel expressed in kidney Mutation in OCRL1 gene—LOWE syndrome Hematuria,nephrolithiasis,nephrocalcinosis,rickets (25%),chronic renal failure Oral phosphorus supplementations

27. Distal renal tubular acidosis AR/AD Manifests as FTT Metabolic acidosis hypercalciuria,nephrocalcinosis Rickets is variable Responds to alkali therapy

28. Summary

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