Transcript
Vit-D resistant ricketsBy
P.Padma Priyanka
Calcium deficiency
Sec. to inadequate dietary calcium Weaning early from breast milk/formula <200mg/day Low intake/malabsorption IV nutrition
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
Phosphorus deficiency
Inadequate intake Isolated malabsorption- aluminium containing
antacids Discontinue antacid and short-term
phosphorus supplementation
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
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
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
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)
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
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
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
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
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
Clinical manifestations
Rickets Abnormalities of lower extremities and poor
growth Delayed dentition Tooth abscesses Hypophosphatemia and short stature without
clinically evident bone disease
Laboratory findings
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
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
Monitoring
Laboratory monitoring ofSerum calciumPhosphorusALPPTHUrinary calciumPeriodic renal ultrasounds
Prognosis
Response to therapy is usually good Girls<boys (probably due to X-linked) Short stature may persist despite healing of
rickets
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
Autosomal resistant hypophosphatemic
ricketsMutation in gene encoding dentin matrix protein 1
Increased FGF-23 levels
Renal phosphate wasting
HypophosphatemiaLow or normal 1,25-
D
Hereditary hypophosphatemic rickets
with hypercalciuriaMutation in gene for Sodium phosphate
cotransporter
Hypophosphatemia
Production of 1,25-D
Increased absoprtion of calcium
Supressing PTH
Hypercalciuria
Rachitic leg abnormalities Muscle weakness Bone pain Short stature Disproportionate decreased length of lower
extremities Nephrolithiasis sec. to hypercalciuria
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
Overproduction of phosphatonin
Tumor-induced osteomalacia(adults>children) McCune-Albright syndrome-triad of polyostotic
fibrous dysplasia,hyperpigmented macules,polyendocrinopathy)
Epidermal nevus syndrome Neurofibromatosis
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
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
Distal renal tubular acidosis
AR/AD Manifests as FTT Metabolic acidosis hypercalciuria,nephrocalcinosis Rickets is variable Responds to alkali therapy
Summary
Thank you
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