Study on the Impact of FOCUS-PDCA Management Model on the Disinfection Qualit...
Approach to a case of vitamin D resistant
1. APPROACH TO A
CASE OF VITAMIN
D RESISTANT
RICKETS
PRESENTED BY:
DR. ADITI TULSIYAN
PG RESDIENT
PAEDIATRICS
2. SOURCES OF VITAMIN D
Cutaneous synthesis
Dietary sources- animal source (Cholecalciferol D2) salmon, cod liver oil, egg yolk
plant source (Ergocalciferoll D3) orange juice, milk
Factors affecting synthesis of Vitamin D in skin
1. Timing of the day
2. Season
3. Skin pigmentation
4. Exposure of skin to UVB
Daily Requirement
Infants 400 IU (10ug)
Children 600 IU (15ug)
Breast milk is poor in Vitamin D (12-40 IU/L)
Dietary Ca Requirement
Infants(0-6 mnths)- 200mg/d
(6-12 mnths)- 260 mg/d
Children >12mnths – 500mg/day
3. VITAMIN D METABOLISM
290-315nm
Absorbed in duodenum
Peripheral conversions occurs in SKIN
COLON MACROPHAGES VASCULAR
SMOOTH MUSCLES BONE PARATHYROID
GLAND
-----INHIBITS ABSOPRTION
OF PHOS FROM DCT
INHIBITS ABSOPRTION
OF PHOS FROM DCT
4. Rickets is a disease of growing bone that is caused by
unmineralized matrix at the growth plate and occurs in
children only before fusion of the epiphyses.
It is derived from the word WRICKETS meaning
TWISTED referring to the characteristic BOW LEGS of
rickets.
The most common cause of rickets is nutritional deficiency
although the incidence of rickets overall has decreased through
the public health measures
5. CAUSES OF RICKETS
VITAMIN D DISORDERS
Nutritional vitamin D deficiency
Congenital vitamin D deficiency
Secondary vitamin D deficiency
Malabsorption
Increased degradation
Decreased liver 25-hydroxylase
Vitamin D謀ependent rickets type 1 A and B
Vitamin D謀ependent rickets type 2 A and B
Chronic kidney disease
CALCIUM DEFICIENCY
Low intake
Diet
Premature infants (rickets of prematurity)
Malabsorption
Primary disease
Dietary inhibitors of calcium absorption
PHOSPHORUS DEFICIENCY
Inadequate intake
Premature infants (rickets of prematurity)
Aluminum-containing antacids
7. 290-315nm
-----INHIBITS ABSOPRTION OF
PHOS FROM DCT
Level is increased in
ADHR ARHR XLHR
INHIBITS ABSOPRTION
OF PHOS FROM DCTVDDR 1
Mutation in gene for vit D
receptor
VDDR2
8.
9. HEAD
Craniotabes(ping pong skull) – occurs due to thinning of inner table
of occipital bone under the pressure
of intracranial contents with failure of mineralization
Can be elicited by gentle pressure with both thumbs
which produces dent with crackling sensation
elicited b/w 3-12 months of life
Frontal Bossing
Craniosyntosis
Delayed closure of fontanels
Delayed Dentition with enamel hypoplasia
Hot cross bun skull (CAPUT QUADRATUM)
11. EXTREMITIES
Enlargement of wrists and ankles d/t physeal overgrowth
Double malleoli
Valgus or varus deformities
Windswept deformity (combination of valgus deformity of 1 leg
with varus deformity of the other leg)
Anterior bowing of the tibia and femur
Coxa vara
Leg pain
Increase fractures (particularly green stick fracture)
String of pearl deformity
12.
13. BACK (RACITIC CAT BACK)
Scoliosis
Kyphosis
Lordosis
HYPOCALCEMIC SYMPTOMS
Tetany
Seizures
Stridor due to laryngeal spasm
Diarrhoea or Constipation
Anemia
GENERAL
Failure to thrive
Listlessness
Muscle Weakness
14. Radiological Findings
Cupping of epiphyseal end
Fraying
Increase in distance between distal end of radius
and metacarpal bones
Rarefaction of Diaphysis
Coarse trabeculation
15. Investigation
Vitamin D status
Based on 25OH level- Best measure to estimate circulating Vitamin D
level because of its minimal regulation
Sufficiency- >50nmol/l
Insufficiency- 30-50 nmol/l
Deficiency - <30nmol/l
1,25 OH LEVEL
S.Ca
S.PO4
ALP
PTH
16.
17. TREATMENT FOR NUTRITIONAL
RICKETS
STOSS THERAPY- 3,00,00-6,00,000 IU/day PO/IM as 2-4 doses over 1 day
2,000-5,000 IU/day over 4-6 week
Calcium supplemenattion (35mg/kg/day)
Followed by daily Vitamin D intake - <1yr- 400IU/day
>1yr- 600 IU/day
Oral calcium – 500mg/day
Calcitriol- 0.05ug/kg/day
Iv calcium- 20mg/kg of CaCl2
100mg/kg of CaGluconate
18. Stoss therapy respond well in case of Vitamin D
deficiency Rickets
Biochemical recovery in few days (96hrs)
EARLIEST biochemical change after starting stoss
therapy- Increase in S.PO4 level
Radiological recovery in 6-7days
19. Response to therapy
Improvement in pain symptoms
Healing of bone malformation
Radiological evidence of healing
zone of provisional calcification appears (WHITE LINE OF FRENKEL)
appears at the end of zone of degeneration
osteoid between this line and diaphysis gradually ossifies
HEALED RICKETS
Bone density returns to normal with slight cupping remains as a stigma of previous
rickets
20.
21. HEALED RICKETS
ABSENT PRESENT
WHITE LINE OF CALCIFICATION
XRAY AFTER 2-4 WEEKS
REPEAT DOSE OF
CHOLECALCIFEROL
PRESENT
White line of calcification
X ray After 2-4 weeks
STOSS THERAPY
ABSENT
HEALED
RICKETS
REFRACTORY
RICKETS
22. CALCIUM DEFICIENCY
Rickets secondary to inadequate dietary calcium
Age of onset- Begins after 6 months of age when child is
being weaned off from breast milk.
Diet rich in phytates, oxalates and phosphates (green
leafy vegetables) leads to decrease absorbtion of
calcium
Risk factors
Malabsorption syndromes
Small bowel resection
Milk allergy
23. Diagnosis
S. Ca - Normal/Decreased
S.Pi - decreased
PTH - Increased
25(OH)D3- Normal
1,25 (OH)D3 –Increased
ALP- Increased
Urinary ca/ pi – DECRERASED
TREATMENT
Calcium supplement
1-3 years (700mg/day)
4-8 years (1000mg/day)
9-18 years (1300mg/day)
24. PHOSPHORUS DEFICIENCY
ETIOLOGY
Inadequate intake
Malabsorption
Rickets of prematurity
Aluminum containing antacids (leads to phosphate chelation)
DIAGNOSIS
S. Ca - Normal
S.Pi - decreased
PTH - N/decreased
25(OH)D3- Normal
1,25 (OH)D3 –Increased
ALP- Increased
Urinary ca/ pi – DECRERASED
26. PHEX GENE- PHosphate regulating gene with homology to Endopeptidase
on X chromoosome
Inactivates FGF 23
HYPOPHOSPHATEMIA DECREASED PRODUCTION OF 1,25D
DECREASED ACTIVITY OF 1a HYDROXYLASE
DECREASED RENAL TUBULAR ABSORBTION OF
PHOSPHATE
INCREASED LEVEL OF FGF 23
MUTATION PHEX GENE
27. CLILNICAL MANIFESTATION
LOWER limb deformities are predominating
feature – COXA VARA
GENU VALGUM
GENU VARUM
DENTAL ABNORMALITIES- Pulp deformities,
recurrent dental abscess
Abnormalities of maxillofacial region
Premature closure of sutures
28. DIAGNOSIS
S. Ca - Normal
S.Pi - Decreased
FGF23- Increased
PTH - Normal
25(OH)D3- Normal
1,25 (OH)D3 –Decreased
ALP- Increased
Urinary ca- Normal
Urinary pi – DECRERASED
29. Treatment
Phosphorus
1-3g /day in 4 divided doses.(frequent dosing reduces diarrhoea)
Calcitriol
30-70 ng/kg /day in 2 divided doses
Osteotomy required for severe bone deformities
Short Stature- Growth Hormone
30. COMPLICATIONS OF TREATMENT
OCCURS IF THE BALANCE BETWEEN PHOSPHORUS AND CALCIUM
IS INADEQUATE
WORSENS BONE LESIONS
SEC HYPERPARATHYROIDISM
DECREASED CALCIUM ABSORTION
INCREASED PHOSPHORUS
HYPERCALCIURIA
NEPHROCALCINOSIS
HYPERCALCEMIA
INCREASED CALCITRIOL
32. DIAGNOSIS
S. Ca - Normal
S.Pi - Decreased
FGF23- Increased
PTH - Normal
25(OH)D3- Normal
1,25 (OH)D3 –Decreased
ALP- Increased
Urinary ca- Normal
Urinary pi – DECRERASED
33. AUTOSOMAL RECESSIVE
HYPOPHOSPHATEMIC RICKETS
TYPE 1 – MUTATION IN DENTIN MATRIX
PROTEIN (DMP1)
TYPE 2- MUTATION IN ENPP1 GENE
Causes arterial calcification of infancy
Both types lead to increase in level of FGF3
34. HEREDITARY
HYPOPHOSPHATEMIC RICKETS
WITH HYPERCALCIURIA AR
Mutation in Sodium Phosphorus
cotransporter in proximal tubule (SLC34A3)
Leg abnormalities are the dominating
symptoms here
Short stature (upper segment>lower segment)
Muscle weakness
Bone Pain
Kidney stones
Hypercalcuria
Supression of PTH
Increased Intestinal absorption of Calcium
INCREASED PRODUCTION OF 1,25D
HYPOPHOSPHATEMIA
MUTATION IN SLC34A3
35. Diagnosis
S. Ca - Increased
S.Pi - Decreased
FGF3- Normal
PTH - Decreased
25(OH)D3- Normal
1,25 (OH)D3 –Increased
ALP- Increased
Urinary ca- Normal
Urinary pi – DECRERASED
39. RICKETS OF PREMATURITY
Risk factors: Prematurity, birth weight<1000g,
complicated neonatal course
prolonged use of parenteral nutrition, use of diuretics and
corticosteroids
Age of presentation: 1-4 months
Presenting Features: Nontraumatic fractures
Respiratory distress d/t atelectatsis and poor ventilation
develops >5 weeks after birth
Enamel Hypoplasia
Dolichocephaly
Rachitic Findings
40. DIAGNOSIS:
S. Ca - N/LOW/HIGH
S.Pi - Decreased
FGF3- Normal
PTH - Decreased
25(OH)D3- Normal
1,25 (OH)D3 –Increased
ALP- Increased (>5-6 times the upper limit of adults)
Urinary ca- Normal
Urinary pi – DECRERASED
SCREENING xray at 6-8 weeks of age for infants who are high risk for
rickets
41. Clinical Approach to A case of
RICKETS
Past History- H/O Recurrent pneumonia, tetanic episodes
H/o oily stool, bleeding or any other history s/o FAT MALABSORPTION
h/s/o chronic liver disease
h/o hematuria, proteinurea, UTI
h/s/o CKD
h/o polyuria (s/o FACONI SYNDROME)
Dietary History- H/o breastfeeding, fortified milk or cow milk
dietary fibres interferes with Calcium absorption
42. ANTENATAL HISTORY- Poor nutrition, inadequate sun exposure
BIRTH HISTORY- Prematurity, birth weight<1000g,
complicated neonatal course
prolonged use of parenteral nutrition, use of diuretics and
corticosteroids
TREATMENT HISTORY – Phenobarbital , Phenytoin- Increases degradation of Vitamin D
Al Containing antacid interferes with Phosphate absorption
Protease inhibitors inhibits cytochrome P450 and decreases production of
active form of Vitamin D
FAMILY HISTORY- H/O previous sibling death (s/o CYSTINOSIS)
Important in many genetic cause of rickets
45. Ca Pi PTH 25OH 1,25 0H2D FGF23 Urine
Pi Ca
VITAMIN D Def N/ N
DIETARY Pi Def N N/ N
DIETARY Ca Def N/ N
VDDR1 N N/HIGH NOT
DETECTABLE
V
VDDR2 N N/HIGH
XLH N N N V
ARHR N N N
ADHR N N N
HHRH N N N N
46. MANAGEMENT
Baesd on the etiology
VITAMIN D Deficieny: vitamin D therapy
Calcium supplementation
Phosphorus
Calcitriol
Orthopedic intervention for bone deformities
Physiotherapy