approach to inborn errors of metabolism .. dr.padmesh

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Approach to Inborn Errors of Metabolism (Pediatrics)

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  • 1. APPROACH TO INBORN ERRORS OF METABOLISM DR.PADMESH.V DEPT OF PEDIATRICS,DR.SMCSI MCH, KARAKONAM.
  • 2. Dr.Padmesh.V METABOLISM Metabolism Catabolism (Breaking down) Anabolism (Building up) Enzymes play an important role in facilitating the process by serving as catalysts in the conversion of one chemical (metabolite) to another.
  • 3. Dr.Padmesh.V Catabolism : Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy.
  • 4. Dr.Padmesh.V Catabolism : Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy.
  • 5. Dr.Padmesh.V Anabolism : Anabolism is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy.
  • 6. Dr.Padmesh.V Anabolism : Anabolism is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy.
  • 7. Dr.Padmesh.V Anabolism : Anabolism is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy.
  • 8. Inborn errors of metabolism (IEM) Dr.Padmesh.V - Inborn errors of metabolism (IEM) are disorders in which there is a block at some point in the normal metabolic pathway - IEMs occur due to mutations in DNA. DNA Enzyme which code for a Receptor Specific protein Transport vehicle Membrane pump Structural element
  • 9. Dr.Padmesh.V Example of mechanisms in IEM:Precursor Substrate End-Product A B C
  • 10. Dr.Padmesh.V Example of mechanisms in IEM:Precursor Substrate End-Product A B C Abnormal metabolic pathway Toxic Metabolite D
  • 11. Dr.Padmesh.V The number of diseases due to inherited point defects in metabolism now exceeds 500. While the diseases individually are rare, they collectively account for a significant proportion of neonatal and childhood morbidity and mortality. Diagnosis is important not only for treatment but also for genetic counselling and antenatal diagnosis in subsequent pregnancies.
  • 12. Dr.Padmesh.V CLASSIFICATION OF IEM:1. Amino acid metabolism2. Carbohydrate metabolism3. Lipid metabolism4. Protein metabolism5. Pigment metabolism6. Unknown biochemical defects
  • 13. Dr.Padmesh.V CLASSIFICATION OF IEM:1. Amino acid metabolism -Phenylketonuria -Tyrosinosis -Albinism -Alkaptonuria -Cystinosis -Cystinuria -Homocysteinuria -Hartnup disease -Maple syrup disease
  • 14. Dr.Padmesh.V CLASSIFICATION OF IEM:2. Carbohydrate synthesis: -Congenital lactose intolerance -Galatosemia -Glycogen storage disease -Diabetes mellitus -Scurvy
  • 15. Dr.Padmesh.V CLASSIFICATION OF IEM:3. Lipid metabolism: -Abetalipoproteinemia -Progressive lipodystrophy -Lipid storage disorders * Gaucher * Neimann-Pick * Tay-sachs * Hyperlipoproteinemia
  • 16. Dr.Padmesh.V CLASSIFICATION OF IEM:4. Protein Metabolism: -Immunoglobulin deficiencies -Absent clotting factors (Hemophilia, Christmas dis, Hypoprothrombinemia) -Metal binding protein deficiency (Wilson hepatolenticular degeneration) -Alpha-1 anti trypsin deficiency
  • 17. Dr.Padmesh.V CLASSIFICATION OF IEM:5. Pigment metabolism: -Porphyrias -Methemoglobinemias -Albinism -Crigler-Najjar dis -Dubin-Johnson dis -Gilbert dis -Rotor synd -Primary hemochromatosis
  • 18. Dr.Padmesh.V CLASSIFICATION OF IEM:6. Unknown biochemical defect: -Osteogenesis imperfecta -Marfan synd -Achondroplasia -Ehler danlos synd
  • 19. Dr.Padmesh.VAPPROACH TO IEM
  • 20. Dr.Padmesh.V1. Suspecting Inborn Errors:
  • 21. Dr.Padmesh.V Suspecting Inborn Errors: Inborn errors should be suspected when HISTORY:(1) Symptoms accompany starting/changes in diet,(2) Children with seizures,(3) Developmental delay,(4) Recurrent vomiting,(5) Unusual odour of urine,(6) Parental consanguinity,(7) Problems suggestive of inborn error such as retardation or unexplained deaths in first- and second-degree relatives.
  • 22. Dr.Padmesh.V Suspecting Inborn Errors: CLINICALLY: IEM must be also considered in the differential diagnosis of Critically ill newborns, Neurodegeneration, Mental retardation , Coarse facies / dysmorphic features, Parenchymal liver disease, Cardiomyopathy, Organomegaly Unexplained acidosis, Corneal opacity, cataract or dislocation of lens, Hyperammonemia, and Hypoglycemia
  • 23. Dr.Padmesh.V Clinical pointers towards specific IEMs:
  • 24. Dr.Padmesh.VInborn Errors of Amino Acid MetabolismAssociated with Peculiar Odour:
  • 25. Dr.Padmesh.VPatterns of Presentation:1. Encephalopathy with or without metabolic acidosis.2. Acute liver disease: - Jaundice alone - Hepatic failure - Neonatal cholestasis - Hypoglycemia3. Dysmorphic features.4. Cardiac disease.5. Diarrhea6. Hepatomegaly +/- Splenomegaly7. Predominant Neurological symptoms
  • 26. Dr.Padmesh.V 1) Encephalopathy with or without metabolic acidosis: Encephalopathy, seizures,and tone abnormalities are predominant presenting features of -organic acidemias, -urea cycle defects,and -congenital lactic acidosis. Intractable seizures are prominent in -pyridoxine dependency, -non-ketotic hyperglycinemia, -molybdenum co-factor defect,and -folinic-acid responsive seizures.
  • 27. 2) Acute liver disease: could manifest as- Dr.Padmesh.V Jaundice alone: -Gilbert syndrome, -Criggler-Najjar syndrome Hepatic failure (jaundice, ascites, hypoglycemia, coagulopathy): -Tyrosinemia, -galactosemia, -neonatal hemochromatosis, -glycogen storage disease type IV. Neonatal cholestasis: -alpha-1 antitrypsin deficiency, -Niemann-Pick

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