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Protocol based approach to metabolic liver disease seema alam
- 1. Protocol based approach to Metabolic liver disease Seema Alam Professor Dept of Pediatric Hepatology, Institute of Liver & Biliary Sciences, New Delhi.
- 2. Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences
- 3. Definition of Metabolic liver disease (MLD) Inborn errors of metabolism in which hepatomegaly and /or abnormal liver function form part of the clinical disease
- 4. Why is MLD important 1. Cryptogenic cases maybe MLD 2. Treatable MLD with dietary change and chelation therapy 3. Patient and graft survival after liver transplant is better in MLD vs non metabolic liver diseases ………..Ped Trans 2010 : 14 ; 796-805 4. Genetic Counselling for the future family Which MLD to detect? There are about 1000 MLDs :Exhaustive lab work up Most enzyme assays not available in India Emphasis on: curable or palliative / LT therapeutic option. INTRODUCTION
- 5. Red Signs to suspect MLD •Consanguinity •Positive Family history / pedigree analysis •Less males: X-linked • Fatty liver of preg & HELLP…..FAO in fetus •Neonatal Deaths in Family, Miscarriages •Recurrence in Catabolic Stress •H/o specific food avoidance •Special odours •Dispropionate secretory liver functions & Encephalopathy/ Albumin/ INR •Failure to thrive, Intractable Rickets • Multisystemic inv: Hypotonia, delayed dev, Cardiomyopathy, Renal tubular acidosis
- 6. Varied Presentations of MLD Sick child Cholestatic liver disease Organomegaly Cirrhosis + Portal HTN PALF Encephalopathic / Reye’s syndrome / Cyclic vomitings
- 7. SCREEN ALL INFANT / CHILD / ADOLESCENT PRESENTING WITH LIVER DISEASE One risk factor for MLD Protocol 1 / 2 /3 /4 /5 Depending on the type of presentation
- 8. Complete enzyme def presents earlier in neonates Energy deficient presents immediately after birth Toxic variety presents after a gap Approach to encephalopathy or Reye’s syndrome or cyclic vomitings Hyperammonia MA + incr lact Hypoglycemia Ketonemia No Yes No Yes Yes FAOD UCD Mitochon dis & OA Protocol 1
- 9. Approach to encephalopathy or Reye’s syndrome or cyclic vomitings MA + incr lact Hypoglycemia No Yes Gluconeo genetic disorders Mitochondrial disorders Protocol 1
- 10. ALF NGRS in urine FBS, urine NGRS AFP ABG, Ketones Galactosemia Tyrosinemia type I HFI Hypoglycemia ± increased lactate AFP Urinary succinyl acetone GALT Urine Chromatography FAOD Mitochondrial Hepatopathy Acylcarnitine profile Urea Cycle defect Plasma Aminoacidogram & Urinary Orotic acid Wolman’s disease Radiology Protocol 2
- 11. Approach to a cholestatic child with suspected MLD Pruritus GGT GGT Yes No Normal / Low High Low Normal / High PFIC 1 / 2 PFIC 3 BASD FAOD Cystic fibrosis Citrullinemia Liver biopsy with immunohistochemist ry Hyperamonemia Plasma aminoacids Low urea Sweat Chloride test PFIC 3 presents at any age Rest present as infantile cholestasis Protocol 3
- 12. Approach to a child with organomegaly with suspected MLDHepatomegaly Hepatosplenomegaly Present Absent GSD Types 1 / 3 • Wilson disease • CESD Niemann Pick type C Gaucher’s ds CESD Liver biopsy with specific enzyme estimation & Mutations Hypoglycemia Elevated lactate Bone marrow aspiration & Bx Urine NGRS Absent Present HFI GSD Type 1 / 3 present in infants Rest may present at any age Protocol 4
- 13. Approach to a cirrhotic child with suspected MLD + Portal HTN (Splenomegaly, vx, collaterals) Bone marrow Liver Copper Perl’s & PAS-Diastase Enzyme estimation Present Absent GSD Type 4 Wilson disease Gaucher’s ds Hemochromotosis Elevated lactate Hypoglycemia Absent Present HFI GSD Type 4 usually presents as infants Rest may present at any age Protocol 5
- 14. ILBS data Cyclic vomitings = 5 Encephalopathy = 3 Hypoglycemia, Elevated lactate, Ketonuria, Absent urine NGRS, Normal NH3 Suspected Gluconeogenetic disorder (Primary lactatemia) Fruc 1,6 biphosphatase Deficiency (n = 3) No indeterminate cases MLD in none
- 15. Protocol 2 Total ALF (n = 78) Younger age-Gp (0-3 yrs), n = 32 Older age-Gp (>3 yrs), n = 46 • Younger children: 11 MLDs 4 Galactosemia 3 Tyrosinemia 1 Mitochondrial Cytopathy 1 Neonatal hemochromatosis 1 HFI 1 Urea cycle defect - ? Partial OTC deficiency in a girl child 5 Indeterminate • Older children: 6 MLDs 6 Wilson’s disease, 7 Indeterminate
- 16. Protocol 3 Total Cholestatic cases (n = 89) Infants, n = 51 Older children, n = 38 Infants: 10 MLDs 1 Cystic fibrosis 8 PFIC type 2 1 NICCD Older children: 14 MLDs All 14 PFIC (Type 1= 1, Type 2 = 11, Type 3 =2) Indeterminate = 2
- 17. Protocol 4 Organomegaly Hepatomegaly, n = 24 Hepatosplenomegaly, n = 7 Hepatomegaly: 24 MLDs 17 GSD Type 3 4 Wilson’s dis 1 Chanarin-Dorfman syndrome 1 OTC, 1 HFI No indeterminate Hepatosplenomegaly: 7 MLDs 2 Gaucher’s disease 2 Hunter’s diseas 1 Cholesterol ester storage disease 2 Neimann Pick Type C
- 18. Protocol 5 Total CLD (n = 219): 39 MLDs 37 Wilson’s disease 1 HFI 1 Juv hemochromatosis 11 Cryptogenic
- 19. Commonest Presentation for MLD was Organomegaly All 31 cases. 21.7 % of 78 ALF had MLD 17.8 % of Cirrhotics 26.9% cholestatic liver dis had MLD Total cases = 417 Total MLD = 119 (28.5 %) Indeterminate = 25 (5.9 %)
- 20. Discussion Arora et al AIIMS Indian Pediatrics 2010 Unknown etiology 237 (28.2%) Metabolic liver diseases 159 (18.9 %) Tropical Gastroenterology 2010;31(2):108–110 Unknown etiology 6 of 45 (13.3%) MLD 11 of 45 cases ( 25 %)
- 21. Take Home Message Protocol based approach can identify MLD and would also help in reducing the cryptogenic or indeterminate liver disease Organomegaly is the commonest presentation of MLD