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

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