Dr Shilpa Dugar ISPGHAN 2018

1. 8 Year Old With Resistant Rickets
Dr. Shilpa Dugar

2. • 8 year / Male
• First issue, non-consanguineous marriage
• Referred as case of bony deformity (knock knee)
History

3. Mild difficulty in walking / running which increased
over the period of 2 years
August 2015 : Received vitamin D. Dose not
known. No clinical improvement
May 2017 : Received 2 doses of vitamin D
(appropriate dose) over a span of 3 months
No clinical and radiological improvement.

4. Hence referred to KEM in view of bony deformity
Looks like ??
Rickets (Resistant)

5. Stepwise approach to Rickets
S. Ca, P, ALP
Low alk phos: hypophosphatasia
Normal: skeletal dysplasia,
PHP type 1
White line of healing on X ray
Refractory rickets
No healing
Nutritional rickets
Vit. D & Ca
Suspect nutritional rickets
Low S. Ca, P ; high ALP, PTH

6. No significant history – fall, polyuria, polydipsia …..
On Examination:
Genu valgum
Intermalleolar distance : 15cm (N <8 )
No dental abnormality
No alopecia
No pallor / icterus
Anthropometry
Height 106cm (<3rd centile)
Weight 22 kg (-1 Z score)
KEM Hospital

7. • CVS / RS / CNS : normal
• Per Abdomen Examination
• Liver 3cm below costal margin,
• Firm. Span 12.5cm.
• Spleen not palpable, no ascitis.

8. Investigations
Lab Parameters Values
CBC 9 / 6500 /2.5
Serum calcium 9.5 mg/dL (N : 9.4-10.3)
Serum phosphorous 1.8 mg/dL (N: 3.6-5.8)
Alkaline phosphate 455 (N: 71-220) )
Urea 22
Creatinine 0.4
eGFR (0.413* ht(cm)/sr creat) = 109 ml/min/1.73 m2.
{N : 90-120}
Parathormone 40 pg/mL (N: 15-65)
25(OH) vitamin D 75 ng/mL (N: >30-70)

9. Serum sodium 135
Serum potassium 3
Serum Chloride 112
VBG
Ph
Pco2
Hco3
7.28
20
12
ANION GAP 11 meq/L {7-16 meq/L)
Urine Ph 4.5
Investigations

10. • Normal anion gap metabolic acidosis
• Normal renal function tests
• Hypokalemia and hypophosphatemia
• Low urine pH
Investigations

11. What It Could Be ??
RENAL TUBULAR ACIDOSIS

12. S Ca, P, ALP, SE, PTH,
Blood urea, S Creatinine, VBG,
Normal/ low P High Phosphate
Normal anion gap metabolic
acidosis: Renal tubular
acidosis
Normal Ca, normal PTH,
high P excretion:
hypophosphatemic rickets
Low Ca, high PTH: VDDR I, VDDR II
High urea, S Cr, High ALP,
high PTH: Chronic Kidney
Disease
Normal urea, S Creatinine,
Low Ca, High PTH:
Pseudohypoparathyroidism
Approach to Refractory rickets

13. Other Findings To Corroborate
 Glucosuria (2+)
 Phosphaturia (FEphosphate = 60% {5-12})
 Aminoaciduria
 Hyperuricosuria
 No hypercalciuria
All of the above findings s/o ??
Proximal RTA

14. Serum Bilirubin 0.4
SGOT 120
SGPT 89
GGT 70
Is There Anything Missing in Investigations ??
Prothrombin time 17.5/12.2 INR 1.4
Serum protein 5.5
Albumin 3
USG Abdomen - altered echotexture of liver
N0 nephrocalcinosis.
What About Firm Hepatomegaly ??

15. Genu valgum, Proximal RTA, Chronic Liver Disease
1. Wilson Disease
2. Tyrosinemia
3. HFI
4. Galactosemia
5. Fanconi Bickel
6. Other…..

16. Further Workup
• Slit lamp : KF ring present
• Serum ceruloplasmin : 4mg % (20-40)
• 24 hr urinary copper : 350 mcg (<100mcg/24h)
Euro Wilson score 6

17. Case Summary
A child with resistant rickets with Wilson Disease with
proximal RTA
How to treat?

18. Treatment
1. Treatment of WD – chelators, zinc
2. Treatment of RTA
 Potassium & Sodium Citrate (Potrate)
- Dose: 2-10meq/kg/day of base.
- Follow up: depends on serum potassium and
bicarb levels, usually every 3monthly.
- Duration : 4-6months, till bicarb levels normal.
 Phosphorous Supplement ( Adphos )
- Dose: 30-60mg/kg/day in 3-4 divided doses.

19. Treatment of Genu Valgum
 Observation
- Genu valgum < 15 degrees in a child < 4 years age
 Bracing
- rarely used as ineffective
• Surgery
- Adolescent with severe genu valgum
- Unilateral genu valgum
- Marked mechanical axis deviation.
Hemiepiphysiodesis or physeal tethering (staples,
screws, or plate/screws) of medial side

20. WD & osseomuscular presentation
 Osteoporosis, osteomalacia, rickets
 Spontaneous fractures, osteoarthritis, osteochondritis
dissecans, chondrocalcinosis
 RTA, hypoparathyroidism, Vit D deficiency, copper toxicity
 Distal / Proximal RTA
 Copper damage to renal tubules
 Treatment with chelators improves RTA

24.  Wilson’s disease may not always have classic
neuropsychiatric and/or hepatic manifestations.
 Rickets- and osteomalacia-like features may be due to
causes other than vitamin D deficiency.
 Wilson’s disease can rarely involve renal tubules and
bone.
 Radiographic evidence of osteoporosis is present in up to
88% of persons with Wilson’s disease.
 Joint involvement, particularly knees and spine, is also
common, and joint pain may be the presenting symptom
of Wilson’s disease.

25.  Low/normal High
Diagnostic Approach To Resistant Rickets
Serum phosphate
VBG,
Electrolytes
Deranged
RFT
Chronic kidney
disease

26. Normal Anion Gap
With metabolic acidosis
VBG, Electrolytes
RENAL
TUBULAR
ACIDOSIS
PTH, calcium
Normal
PTH + calcium
VITAMIN D
DEPENDENT RICKETS
HYPOPHOSPHATEMIC
RICKETS
Serum PTH, calcium
Normal

27. FEATURES GALACTOSEMIA TYROSINEMIA WILSON
AGE 1-6 months. 1-6months. Older
children.
Usually >3yrs
PRESENATATION Acute Liver Failure
H/O neonatal
sepsis(gr –ve)
Acute Liver Failure.
Hypotonic, rickets
hepatospleenomeg
aly
Heaptic Neurowilson
Haematological
Skeletal
Psychiatric
COAGULOPATHY
/Deranged PT
+ + +
BILIRUBIN Fluctuating levels.
Indirect/direct
Direct Direct
HAEMOLYSIS + -/+ + esp in ALF
URINE Reducing
substance +
N 24 hr urinary copper
>100mcg/24hrs
OPTHAL
EXAMINATION
Oil drop cataract - KF ring + on SLIT
LAMP
SPECIFIC GAL-1-PUT
enzyme
AFP >40,000-2lac
mg/L. urinary
succinyl acetone
Serum ceruloplasmin
<20mg/dL

28.  Fanconi bickel:
 1. Age :
 Infancy :recurrent vomiting, fever, failure to thrive.
 Early childhood: short stature,protuberant
abdomen,moon shaped facies.
 Diagnosis :
 1. Fasting hypoglycemia, postprandial
hypergalactosemia.
 2. mildly deranged LFTs & renal tubular reabsortion
defects
 3. urine: galactosuria,glycosuria.

29. Monitoring
 Hepatic wilson:
 Start with chelator( penicillamine )& zinc acetate.
 Urine routine/CBC after 1week: no proteinuria &
thrombocytopenia : shift to full dose.
 Indicators for response ?
 1. KF ring disappear in 6months
 2. LFTs esp PT settles gradually in 6months-1yr.
 Long term follow up:
 Repeat 24hr urinary copper/ zinc/ LFTs: every 6monthly
 Target for 24hr urinary copper excretion >150mcg/24hr.
 Target for 24hr urinary zinc excretion >2mg/24hr.
 KF ring on slit lamp & Usg Abdomen alternate yr.

30. Treatment Of Wilson With RTA
Drugs Dose Adverse effect caution
Penicillamine
Drug of
choice
20-25m/kg/day
TID
Proteinuria
Bone marrow
depression(platelet)
Rash. Pyridoxine
def.
Gradually increase in
neurowilson.
Empty stomach (1hr
prior to food)
8hr gap :between
subsequent doses.
Zinc
Acetate(maint
enance)
<40kg 25mg TID
>40kg 50 TID
Gastritis 1 hr prior to food. 8hr
gap :between
subsequent doses.
Trientine(1st
line for
neurowilson)
2-12 yrs: 300mg BD
12-18yrs:300-
600mg BD
SLE and severe
bone marrow
depression
Frequent blood
monitoring