This document summarizes various causes of rickets, including calcium deficiency, phosphorus deficiency, rickets of prematurity, and several genetic disorders. Calcium deficiency can result from low dietary intake or malabsorption and presents with signs of rickets in infancy. Phosphorus deficiency is usually due to inadequate intake or antacid use. Rickets of prematurity occurs in very low birth weight infants and is prevented by mineral supplementation. The document also describes several genetic causes of rickets, including X-linked hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, and Fanconi syndrome. Treatment involves calcium, vitamin D, and phosphorus supplementation tailored to the specific deficiency.

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

4. 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

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

6. Rickets of prematurity
 Very low birthweight infants(<1000g) and younger
gestational age
 Transfer of calcium and phosphorus 80% occurs in 3rd
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

7. 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

8. 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

9.  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)

10. Diagnosis
 Screening tests-weekly measuremen tof
calcium,phosphorus and ALP
 Serum HCO3
- as metabolic acidosis causes bone
dissolution
 Atleast 1 screening x-ray at 6-8weeks

11. 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

12. 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

15. Pathophysiology
 Defective gene- PHEX gene
 Phosphate-regulating gene with homology to
Endopeptidases on the X-chromosome
 Indirect role in inactivating the
phosphatonin(humoral mediator) FGF-23
 Mutations in PHEX increased levels of FGF-23

16. Mutation of PHEX gene
Increased levels of FGF-23
Decreased phosphate
reabsorption in proximal tubule
Increased phosphate excretion
Inhibits renal 1α-hydroxylase
Decreased production of 1,25-
D

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

18. Laboratory findings

19. 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

20. Complications of
treatment
 Occurs when there is not adequate balance
Increased
phosphorus
Decreased calcium
absorption
Sec.
hyperparathyroidism
Worsen bone
lesions
Increased
calcitriol
Hypercalciuria
Nephrocalcinosis
hypercalcemia

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

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

23. Autosomal dominant
hypophosphatemic rickets
Mutation in dene
encoding FGF-23
Prevents degradation
of FGF-23
Increased levels of
phosphatoin
Hypophosphatemia
Elevated ALP
Low or normal 1,25-D

24. Autosomal resistant
hypophosphatemic rickets
Mutation in gene
encoding dentin matrix
protein 1
Increased FGF-23 levels
Renal phosphate wasting
Hypophosphatemia
Low or normal 1,25-D

25. Hereditary hypophosphatemic
rickets with hypercalciuria
Mutation in gene for Sodium
phosphate cotransporter
Hypophosphatemia
Production of 1,25-D
 Increased absoprtion of
calcium
Supressing PTH
Hypercalciuria

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

27.  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

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

29. Fanconi syndrome
 Sec. to generalized dysfunction of the renal proxinal
tubule
 Loss of phosphate,AA,HCO3
-,glucose,urate etc.
 Some-partial dysfunction
 Hypophosphatemia,renal tubular acidosis
 Rickets+bone dissolutionFTT

30. 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(2
5%),chronic renal failure
 Oral phosphorus supplementations

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

32. Summary

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