Case PresentationA case of recurrent vomiting Dr Nilam Thaker Pediatric Nephrologist Ahmedabad
Male/15 monthsC/O failure to thrive vomiting off and on 6-7 month of age abdominal distensionNo h/o diarrhoea/constipation fever/cough/cold/breathlessness jaundice
H/O Polyuria & polydipsiaNo H/O dysuria or straining while passing urine bony deformity visual or hearing problem convulsion/change in sensorium
Born full term Birth weight – 2.5 kg No perinatal problem Apparently normal till 4-6 month of age
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
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
Clinical impression:“Failure to thrive with anemia with hepatomegaly “ to rule out - liver disorder - renal tubular dysfunction
Investigations at 9 months( July 2010)Hb 8.3Bilirubin(T/D/I) 0.3/0.1/0.2OT/PT 131/132, GGT 126, Alkaline phophatase 237Albumin/globulin 4.7/1.9 PT/APTT normalBlood sugar( after 12 hrs fasting) 61Triglycerides 219, CPK 51 25 OH vitamin D level 15.4ng/mlLiver Bx: marked micro- macro vesicular steatosis of most of hepatocytes
Provisional diagnosis was kept as GSD type IIITreatment given Calcirol sachet Rocaltrol Vitamin K 5 mg every monthly Multivitamins Diet- corn starch
After 7-8 months of above Rx, his symptoms were persistent in form of persistent vomiting and failure to thriveRequired 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
Investigated at 15 month of age ( 3/2/11)SGOT 508, SGPT 901, GGT 36 Urine Ca/Creat ratio 1.32VBG: PH-7.25, PCO2 35.2, HCO3 15.3, Urine sugar nil, RBS 65Na 129, K 3.82, Cl 96AG : 17.7(high) Treatment given: Potassium citrate,Lactate 2.9mmol/l sodamint tab,Urea 22, Creatinine 0.35 DomstalCalcium, Phosphorous normal
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)
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 hypercalciuriaAny clue???
Detailed History takenVomiting particularly when given sweet food, fruitsTolerated salty food without any vomiting
Kept on- fructose free diet Potassium citrate, sodamint Iron/ folic acidWith in 1 month weight gain of 1.4 kg no vomiting playful
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 electrolytesInvestigated for anemia S.Iron, Transferrin saturation - normal S.Ferritin 12.1(low) Hb elecrophoresis: B thalessemia trait
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
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
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.
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
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
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
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
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
Treatment Avoidance of fructose, sucrose and sorbitol containing food Treatment of complications - liver dysfunctions - renal fanconi syndrome
Prognosis Excellent for infants who receive rapid diagnosis and treatment. In the absence of substantial hepatic damage, life expectancy is normal.
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