1. Case Presentation
A case of recurrent vomiting
Dr Nilam Thaker
Pediatric Nephrologist
Ahmedabad

2. Male/15 months
C/O
 failure to thrive
 vomiting off and on 6-7 month of age
 abdominal distension
No h/o diarrhoea/constipation
fever/cough/cold/breathlessness
jaundice

3. H/O
 Polyuria & polydipsia
No H/O
 dysuria or straining while passing urine
 bony deformity
 visual or hearing problem
 convulsion/change in sensorium

4.  Born full term
 Birth weight – 2.5 kg
 No perinatal problem
 Apparently normal till 4-6 month of age

5. 6 – 9 months
 Vomiting started at 5-6 month of age, not relieved by
treatment
 Investigated for vomiting and abdominal distension at Bhopal
 Had hepatomegaly with abnormal liver enzymes
 Referred to higher center to rule out liver disorder

6.  S/H: only sib
 F/H:
 Grand father(paternal) expired due to renal failure
secondary to diabetes
 Grand father(maternal)- diabetic with renal stone
 mother’s both uncle diabetic with renal failure, on dialysis
 Milestones: mild delay of motor milestones

7. G/E :
Weight 7.6 kg, Height 73cm(expected 10.5kg/78 cm)
Vitals stable
Pallor present
S/E :
Hepatomegaly 7 cm bcm, firm, nontender
rest unremarkable

8. Clinical impression:
“Failure to thrive with anemia with hepatomegaly “
to rule out
- liver disorder
- renal tubular dysfunction

9. Investigations at 9 months( July 2010)
Hb 8.3
Bilirubin(T/D/I) 0.3/0.1/0.2
OT/PT 131/132, GGT 126, Alkaline phophatase 237
Albumin/globulin 4.7/1.9 PT/APTT normal
Blood sugar( after 12 hrs fasting) 61
Triglycerides 219, CPK 51
25 OH vitamin D level 15.4ng/ml
Liver Bx: marked micro- macro vesicular steatosis of most of
hepatocytes

10. Provisional diagnosis was kept as GSD type III
Treatment given
 Calcirol sachet
 Rocaltrol
 Vitamin K 5 mg every monthly
 Multivitamins
 Diet- corn starch

11. After 7-8 months of above Rx, his symptoms were persistent in form of
persistent vomiting and failure to thrive
Required 3 times hospitalization ( between 8-15 month)
- Electrolyte imbalance in form of hypokalemia, hyperchloremia
- Acidosis
- Deranged liver enzymes
- USG : diffuse enlargement of liver with fatty infiltration
nephrocalcinosis
?? Renal tubular disorder

12. Investigated at 15 month of age ( 3/2/11)
SGOT 508, SGPT 901, GGT 36
Urine Ca/Creat ratio 1.32
VBG: PH-7.25, PCO2 35.2,
HCO3 15.3,
Urine sugar nil, RBS 65
Na 129, K 3.82, Cl 96
AG : 17.7(high)  Treatment given:
Potassium citrate,
Lactate 2.9mmol/l
sodamint tab,
Urea 22, Creatinine 0.35 Domstal
Calcium, Phosphorous normal

13. After 3 weeks of treatment
 Urinary complaints( polyuria) decreased
 Vomiting off and on continued
 During episodes of vomiting, blood sugar always
remained > 60
 Weight loss of 300gm (7.6 to 7.3 kg)

15. Case reviewed and history retaken
 Well till about 5-6 months
 No significant hypoglycemia
 No huge hepatomegaly
 Persistent vomiting
 FTT
 Abnormal LFTs
 Tubular dysfunction with hypercalciuria
Any clue???

16. Detailed History taken
Vomiting particularly when given sweet food, fruits
Tolerated salty food without any vomiting

17. Guess what???????

18. Suspected
“ Hereditary Fructose Intolerence”

19. Kept on- fructose free diet
Potassium citrate, sodamint
Iron/ folic acid
With in 1 month
weight gain of 1.4 kg
no vomiting
playful

20. After 4 months of fructose free diet
 Weight gain of 2.6 kg
 No vomiting, polyuria
 Anemic, Hb remained between 8-9
 Acidosis improved, normal electrolytes
Investigated for anemia
S.Iron, Transferrin saturation - normal
S.Ferritin 12.1(low)
Hb elecrophoresis: B thalessemia trait

21. Blood sent for genetic testing for confirmation of HFI
DNA screened for mutations and large scale
deletions/duplications in coding axons 2-9 of the ALDOB gene
Fluorescent sequencing analysis
s/o Homozygous for c.324+1G>A ALDOB mutation

22. date weight height remarks
3/2/11 7.6 73cm
26/2/11 7.3 Kept on fructose
free diet
23/3/11 8.7 75.5
3/5/11 9.2 76.3
4/7/11 9.9 80
7/9/11 10.1
21/10/11 10.3 82.2
1/12/11 10.9 83.4
2/4/12 11.5 86.5

23. date PH HCO3 Lactate Na K Cl
3/2/11 7.25 15.3 2.9 129 3.82 96 Uriliser
Soda bicarb
12/2/11 7.34 10.9 5
26/2/11 7.33 18.9 2.6 137.6 4.49 103.4 Fructose
free diet
4/4/11 7.39 21.8 145 5.08 101
3/5/11 7.37 16.2 134 5.26 97 Incresed
soda bicarb
4/7/11 7.40 18.9
5/9/11 7.36 22.7 140.4 3.98 99.3
21/10/11 7.4 21.9
2/4/12 7.43 23 140.6 4.34 102.3

24. Urine Ca/Creat ratio: ( normal<0.2)
date Urine Ca/creat ratio
22/1/11 1.75 Rocaltrol stopped
4/2/11 1.32 Uriliser started
5/4/11 0.02
2/12/11 0.42
3/4/12 0.38

25. date Bilirubin SGPT SGOT GGTP Protein SAP
(T/D/I) (alb/glob)
8/7/10 0.4/0.1/0.3 132 131 126 4.7/1.9 237
1/10/10 0.2/0.1/0.1 169 111 52 4.5/2.5 192
30/11/10 0.3/0.1/0.2 96 53 4.8/2.3 215
22/1/11 0.2/0.1/0.1 1692 1085 27 301
3/2/11 901 508 36
4/4/11 0.18/0.06/0.12 136 3.93/2.18 276
4/7/11 88 494
2/4/12 0.55/0.09/0.46 160 75.4 4.26/2.72 75.4

26. Present treatment:
 Fructose free diet
 Potassium citrate
 Sodium bicarbonate
 Iron
 Multivitamin
 Udiliv

27. Hereditary Fructose Intolerence
 Disorder of fructose metabolism
 Deficiency of Aldolase B
 Autosomal recessive
 Incidence 1 in 20000 to 1 in 100000 people
 Most cases reported from Europe and North America

28. Fructose metabolism
fructose
fructokinase
fructose 1 phosphate
aldolase B
triose phosphate
gluconeogenesis glycolytic pathway
glucose pyruvate
glycogen
triglyceride

29. FRUCTOSE METABOLISM
Hereditary fructose-
1,6-bisphosphatase
deficiency results in
severely impaired
hepatic
gluconeogenesis and
leads to episodes of
hypoglycemia, apnea,
hyperventillation,
ketosis and lactic
acidosis.

30. Aldolase B
Three isoenzymes of aldolase- A,B,C
Aldolase A – expressed in muscle
Aldolase B- exclusively expressed in liver, kidney, intestine
Aldolase C- expressed in brain

31. Lack of aldolase B
 Impaired gluconeogenesis and glycolysis
 Accumulation of fructose 1 posphate leads to
- decrease in ATP by causing sequestration of
inorganic phosphate
- increase in uric acid, magnesium, lactic acid
 accumulation of fructose leads to dysfunction of liver,
kidney and intestine

32. Clinical features
 Neonate and infant exclusive on breast feeding- no symptoms
 After consumption of fructose containg food,
- nausea, vomiting, diarrhoea
- sweating, giddiness (hypoglycemia)
- fatigue, sometime convulsion, coma
 self-protective aversion to foods containing fructose

33. Clinical features
Long term effects:
Failure to thrive
liver : hepatomegaly, deranged liver function, cirrhosis
Kidney : Fanconi syndrome( proximal tubular
dysfunction)
metabolic acidosis, electrolyte imbalance,
phosphaturia, aminoaciduria, hypercalciuria
nephrocalcinosis

34. Diagnosis
 fructose tolerance test
fructose is injected intravenously and glucose, fructose, and
phosphate levels in the blood are monitored. In HFI, glucose
will not rise after fructose injection.
 Biopsy of liver
determining of activity of fructose-1-phosphate aldolase.
 Molecular analysis of DNA
mutation in aldolase B gene located on chromosome 9q22.3.5

35. Treatment
 Avoidance of fructose, sucrose and sorbitol containing
food
 Treatment of complications
- liver dysfunctions
- renal fanconi syndrome

36. Prognosis
 Excellent for infants who receive rapid diagnosis and
treatment.
 In the absence of substantial hepatic damage, life
expectancy is normal.