vitamin d resistant rickets
TRANSCRIPT
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Vit-D resistant ricketsBy
P.Padma Priyanka
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Calcium deficiency
Sec. to inadequate dietary calcium Weaning early from breast milk/formula <200mg/day Low intake/malabsorption IV nutrition
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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 defTreatment - 700(1-3y) 1000(4-8y) 1300 (9-18y)mg/day
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Phosphorus deficiency
Inadequate intake Isolated malabsorption- aluminium containing
antacids Discontinue antacid and short-term
phosphorus supplementation
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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
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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
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Laboratory findings
Low serum phosphorus Low urine phosphate level(reabsorption is
>95%) Normal 25-D High 1,25-Ddemineralization Serum calcium low,normal,high and
hypercalciuria Increaed ALP
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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)
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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
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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
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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
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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
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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
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Clinical manifestations
Rickets Abnormalities of lower extremities and poor
growth Delayed dentition Tooth abscesses Hypophosphatemia and short stature without
clinically evident bone disease
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Laboratory findings
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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
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Complications of treatment
Occurs when there is not adequate balance Increased
phosphorus
Decreased calcium
absorption
Sec. hyperparathyroid
ism
Worsen bone lesions
Increased calcitriol
HypercalciuriaNephrocalcinosi
shypercalcemia
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Monitoring
Laboratory monitoring ofSerum calciumPhosphorusALPPTHUrinary calciumPeriodic renal ultrasounds
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Prognosis
Response to therapy is usually good Girls<boys (probably due to X-linked) Short stature may persist despite healing of
rickets
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Autosomal dominant hypophosphatemic
ricketsMutation in dene encoding FGF-23
Prevents degradation of
FGF-23
Increased levels of phosphatoin
Hypophosphatemia Elevated
ALP Low or normal
1,25-D
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Autosomal resistant hypophosphatemic
ricketsMutation in gene encoding dentin matrix protein 1
Increased FGF-23 levels
Renal phosphate wasting
HypophosphatemiaLow or normal 1,25-
D
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Hereditary hypophosphatemic rickets
with hypercalciuriaMutation in gene for Sodium phosphate
cotransporter
Hypophosphatemia
Production of 1,25-D
Increased absoprtion of calcium
Supressing PTH
Hypercalciuria
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Rachitic leg abnormalities Muscle weakness Bone pain Short stature Disproportionate decreased length of lower
extremities Nephrolithiasis sec. to hypercalciuria
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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
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Overproduction of phosphatonin
Tumor-induced osteomalacia(adults>children) McCune-Albright syndrome-triad of polyostotic
fibrous dysplasia,hyperpigmented macules,polyendocrinopathy)
Epidermal nevus syndrome Neurofibromatosis
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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 dissolutionFTT
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Dent disease
X-linked disorder Mutation in gene coding for chloride channel
expressed in kidney Mutation in OCRL1 gene—LOWE syndrome Hematuria,nephrolithiasis,nephrocalcinosis,ric
kets(25%),chronic renal failure Oral phosphorus supplementations
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Distal renal tubular acidosis
AR/AD Manifests as FTT Metabolic acidosis hypercalciuria,nephrocalcinosis Rickets is variable Responds to alkali therapy
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Summary
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Thank you