A case of nephromegaly
Upcoming SlideShare
Loading in...5
×
 

Like this? Share it with your network

Share

A case of nephromegaly

on

  • 1,548 views

 

Statistics

Views

Total Views
1,548
Views on SlideShare
1,548
Embed Views
0

Actions

Likes
0
Downloads
4
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

A case of nephromegaly Presentation Transcript

  • 1. Case PresentationA case of Nephromegaly Dr Nilam Thaker Pediatric Nephrologist Ahmedabad
  • 2. Female / 20 months 20/9/11 Failure to gain weight and height since 1 yearNegative history for: Repeated fever/cough/cold Vomiting/diarrhoea Urinary complaints(polyuria/polydipsia) Convulsion/behavior changes Bony deformity
  • 3.  Born full term with birth weight – 3.2kg Apparently normal for first 6 – 8 months, had an episode of diarrhoea lasted for 4-5 days at 8 months followed by failure to thrive. She was given AKT for 6 months outside !! Delayed motor milestones ( not able to stand or walk) Only sib No significant family history
  • 4. General ExaminationVitals stable, BP 92/48Pallor present,Features of rickets present(wrist widening, open AF, rickety rosary)Weight – 6.9kg, Height 70cm ( expected 11kg , 84 cm)
  • 5. Systemic Examination P/A Bilateral enlarged palpable kidneys Hepatomegaly 4 cm, firm Splenomegaly 2 cm CVS systolic murmur RS, CNS unremarkable
  • 6. Clinical impressionFailure to thriveAnemiaRicketsBilateral nephromegalyHepatosplenomegaly? CHD
  • 7. Investigations Hb 9, TLC 6600, Platelet 3 lac Urea 15, Creatinine 0.4 Bilirubin ( T/D/I) 1.6/0.8/0.8, SGPT 38 S Protein (T/A/G) 5.5/3.4/2.1 SAP 867 Urine routine normal
  • 8. InvestigationUSG Abdomen:Kidneys- RK 93 X 44, LK 98X 44 both enlarged increased echogenicity, normal CMD. No stone, HDN, cysts or focal lesionLiver- enlarged with diffusely altered echotexture, no focal mass lesion; CBD,PV- NSpleen- enlarged with normal echotexture
  • 9. D/D of Bilateral enlarged kidneys Polycystic kidneys Hydronephrosis Pyelonephritis Nephrotic syndrome Storage disorders: GSD type I Tyrosinemia Amyloidosis
  • 10. My suspected diagnosis…. ? Storage disorder with secondary involvement of kidneys ? Hematologic disorder involving kidneys and liver ? Polycystic kidneys
  • 11. Further investigations Hb 7.8, TLC 7400, Platelet 1.27lac PS : hypochromic microcytic RBCs Ca 8.29, Phosph 2.52, SAP 960 Blood gas: PH 7.38, PCO2 39, HCO3 23.6 Na 143.4, K 3.58, Cl 102.2 X ray wrist s/o rickets ECHO Apical muscular VSD
  • 12. Advised further Ix, but not ready to stayTreatment given Calcirol 1 sachet daily 10 d Calcimax-P Iron Multivitamin
  • 13. Follow up : ( 20 days)Rickets was improving…I was still suspecting ◦ ?storage disorder ◦ ? Hematologic disorder with secondary renal involvementGastroenterologist and hemato oncologist’s opinion taken.
  • 14. Summary of proceedings so farWe have a case who presented ◦ with renal complaints, ◦ and then during the work-up found to have liver involvement which was not advanced on presentation Differential diagnosis? Further work-up?
  • 15. Conditions with liver & kidney involvement Wilson’s GSD type-I Galactosemia Hereditary Fructose Intolerance Tyrosinemia type I
  • 16. Further Investigations Urine for metabolic screen Positive for reducing substance, fructose, proteins. TMS Aminoacid profile s/o raised tyrosine level Tyrosine trial I – 317.35µM trial II – 330.36µM (normal 20-275)
  • 17. Confirmation Succinyl acetone study from urine by GC-MS study Urine GC-MS: Significant elevation of succinyl acetone 4 hydroxy phenyl pyruvate 4 hydroxy phenyl lactateS/O Tyrosinemia type-I
  • 18. Further Ix 30/11/11Blood Unit Ref rangeSuccinyl µmol/L <0.1 5.9acetoneTyrosine µMol/L 50-130 446.1Phenylalanine µMol/L 40-120 74.16Methionine µMol/L 20-50 426.23Alpha feto µgm/L <12 35,556proteinUrineSuccinyl µmol/mmol 0-2 314.88acetone creatinine
  • 19. Tests 30/11/11 Normal valueTotal Bilirubin 1.6 mg/dl 0-1Direct Bilirubin 0.5 mg/dl 0-0.6Indirect Bilirubin 1.1 mg/dl 0-0.4SGOT 90 IU/L 15-45SGPT 53 IU/L 10-40GGTP 200U/L 8-78Alkaline phosphatase 1175 IU/L Up to 390Total protein 4.7 gm% 6.3-8.6Albumin 2.9 gm% 3.7-5.6Globulin 1.8 gm% 1.5-3.5A:G Ratio 1.61 0.9-2
  • 20. Tests 30/11/11 Normal rangecalcium 8.5 mg/dl 8.1-10.4Phosphorous 1.3 mg/dl 4-7Sodium 145 135-145Potassium 2.6 3.5-5.3Chloride 132 96-109HCO3 16 22-26Creatinine 0.3 0.3-0.7
  • 21. Urine phosphate 9.98mg/dl FEP 27 s/o TRP 73 ( N 85-95%) phosphate TmP GFR 1.3 ( N 2.9-4.6) leak
  • 22. MRI Abdomen Hepatomegaly with cirrhotic changes & multiple siderotic nodules. No evidence of mass leasion Moderate splenomegaly Moderately enlarged kidneys with parenchymal disease No evidence of lymphadenopathy or ascites
  • 23. Treatment given Diet low in tyrosine and phenylalanine avoid milk/ dry fruit / high protein food Tab NTBC (Nitisinone) 2mg daily after food bd Syp Potassium citrate 4ml bd Syp Joulie solution 2.5 ml qdsAdvised to come for follow up afterone month
  • 24. Came after 4 monthsBlood Unit Ref range 30/11/11 3/4/12Succinyl µmol/L < 0.1 5.9 <0.1acetoneTyrosine µMol/L 50-130 446.1 501.25Phenylalanine µMol/L 40-120 74.16 129.33Methionine µMol/L 20-50 26.234 21.20Alpha feto µgm/L <12 35,556 3093proteinUrineSuccinyl µmol/mmol 0-2 314.88 0.08acetone creatinine
  • 25. Tests 30/11/11 3/4/12 Normal valueTotal Bilirubin 1.6 mg/dl 1.2 0-1Direct Bilirubin 0.5 mg/dl 0.7 0-0.6Indirect Bilirubin 1.1 mg/dl 0.5 0-0.4SGOT 90 IU/L 64 15-45SGPT 53 IU/L 74 10-40GGTP 200U/L 350 8-78Alkaline 1175 IU/L 321 Up to 390phosphataseTotal protein 4.7 gm% 6.1 6.3-8.6Albumin 2.9 gm% 4 3.7-5.6Globulin 1.8 gm% 2.1 1.5-3.5A:G Ratio 1.61 1.9 0.9-2
  • 26. Tests 30/11/11 3/4/11 Normal rangecalcium 8.5 mg/dl 9.1 8.1-10.4Phosphorous 1.3 mg/dl 8.6 4-7Sodium 145 128 135-145Potassium 2.6 5.3 3.5-5.3Chloride 132 98 96-109HCO3 16 13 22-26Creatinine 0.3 0.3 0.3-0.7
  • 27. Treatment modified Joulie solution stopped Potassium citrate decreased Tab sodamint added Tab NTBC continued
  • 28.  Thus there is marked improvement in biochemical profile related to tyrosine metabolism. However morphological changes in liver appear quite severe, but hopefully should improve if we believe the literature.
  • 29. Tyrosinemia Inborn error in the degradation of the amino acid tyrosine. Autosomal recessive. Three types (type I, type II, type III).
  • 30. TAT- tyrosine aminotransferase Phenylalanin 4 HPPD - 4 OH phenylpyruvate dioxygenase FAH – fumeryl acetoacetate hydrolase Tyrosine TAT Tyrosinemia II 4 hydroxy phenyl pyruvate4HPPD Tyrosinemia III Homogentisate Maleylacetoacetate Fumeryl acetoacetate FAH Tyrosinemia I Fumerate Acetoacetate
  • 31. Tyrosinemia type I Deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). Gene for FAH enzyme located on chromosome 15 More than 30 mutation Incidence is 1 in 100000 worldwide
  • 32. Tyrosinemia type I Phenylalanin Tyrosine Fumeryl acetoacetate Succinylacetoacetate Enzyme defect succinyl acetone inhibit Fumerate Acetoacetate δ ALAporphobilinogen
  • 33. Pathophysiology Fumarylacetoacetate and maleylacetoacetate : alkylating agents hepatorenal damage mutagenic properties hepatocellular carcinoma
  • 34. Succinylacetone inhibits tubular transport of glucose aminoacids Phosphate inhibits porphobilinogen synthase accumulation of -aminolevulinate acute porphyria-like neurological symptoms
  • 35.  Liver: severe liver disease with coagulopathy cirrhosis hepatocellular carcinoma Kidneys: tubular dysfunction aminoaciduria, glucosuria, acidosis phosphaturia --- rickets Nervous system: acute peripheral neuropathy painful paraesthesias neurologic crisis
  • 36. Clinical presentation Less than 6 months of age Severe liver involvement with ascites, jaundice, GI bleed More than 6 months of age Renal tubular dysfunctions with acidosis, failure to thrive, rickets hepatosplenomegaly nephromegaly peripheral neuropathy
  • 37. Diagnosis Increased succinylacetone concentration in the blood and urine Elevated plasma concentrations of tyrosine; methionine, and phenylalanineDefinative diagnosis FAH enzyme activity in skin fibroblasts Mutation analysis of FAH gene
  • 38. TreatmentDiet Restriction of phenylalanin and tyrosine avoid milk and milk product, dry fruits, high protein food allows control of acute crises does not prevent progression of the illness
  • 39. NTBC: ( Nitisinone)2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione Inhibition of 4-hydroxyphenylpyruvate dioxygenase. Effect : abolition of the production of the metabolites responsible for the pathogenesis of the disease Dose: 0.5 to 2 mg/kg/d
  • 40. http://www.childrenshospital.org/newenglandconsortium/NBS/descriptions/images/tyro3.gif
  • 41. Liver transplantationReserved for those children who have severe liver failure at clinical presentation and fail to respond to nitisinone therapy have documented evidence of malignant changes in hepatic tissue
  • 42. Prognosis Very good with NTBC Reversal of morphological changes Need for liver transplant may no longer be there