Maple Syrup Urine Disease

Explaining the mechanism and management of a metabolic disorder Maple Syrup Urine Disease

1. MAPLE SYRUP URINE DISEASE It’s Mechanism and Management Presented by, Pavithra B R BSc Microbiology

2. INTRODUCTION

3. MSUD is a Genetic Metabolic Disorder Inherited from Parents Urine People with this condition has the odour of maple syrup or burnt sugar in their urine.

4. MAPLE SYRUP URINE DISEASE Leucine Isoleucine Valine 2-ketoisocaproate 2-keto-3-methylvalerate 2-ketoisovalerate Branched Chain α -ketoacid Dehydrogenase (BCKD) Deficiency of an enzyme complex The body cannot properly breakdown certain part of protein building blocks. MSUD is characterized by deficiency of an enzyme complex (branched chain alpha keto acid dehydrogenase) that is required to breakdown the three branched chain amino acids (BCAA's) leucine, isoleucine and valine in the body. The result of this metabolic failure is that all three BCAA's, along with a number of their toxic by-products, build up in the body and all accumulate abnormally.

5. MAPLE SYRUP URINE DISEASE Distribution MSUD is very rare. It occurs in about 1 in 185,000 births worldwide. Small gene pool. W hen cousins and other close relatives have children together. About 2,000 people in the United States live with MSUD. It affects males and females equally.

6. SYMPTOMS

7. MAPLE SYRUP URINE DISEASE Symptoms Urine smell like Maple Syrup Poor Feeding Vomiting Weight Loss The symptoms and severity of MSUD varies greatly from patient to patient and largely depends upon the amount of residual enzyme activity.

8. MAPLE SYRUP URINE DISEASE Symptoms Irregular sleep pattern Breathing difficulties Near-sightedness Flush around the cheeks Long limbs If untreated, MSUD can lead to coma or death.

9. MAPLE SYRUP URINE DISEASE Types

10. MECHANISM

11. Valine Isoleucine Leucine Branched-Chain Amino Transferases (BCAT) α -ketoacids Step 1 T he first step in a branched amino acid metabolism involves the enzyme branched chain amino transferase . This enzyme converts the three branched chain amino acids valine, isoleucine and leucine into α - ketoisovalerate , α - keto- β - methylvalerate and α - ketoisocaproate . So, these three are known as α -keto acids.

12. Step 2 Branched Chain Ketoacid Dehydrogenase (BCKD) Maple Syrup Urine Disease Irreversible step

13. O nce we have the three alpha keto acids, they can be acted on into the second step by the enzyme branched chain alpha-ketoacid dehydrogenase to produce a variety of metabolites like Propionyl CoA, Acetyl CoA and Isovaleryl CoA. This step is an irreversible step. T hese metabolites can be further processed into other metabolites that can be used in the TCA cycle. Now, what happens in maple syrup urine disease is that the enzyme branched chain alpha-ketoacid dehydrogenase is dysfunctional. So, what happens is we can’t actually process the alpha keto acids or the branching amino acids any further. So, we get an increase in concentration of valine, isoleucine and leucine along with the keto acids themselves. Maple Syrup Urine disease Mechanism

14. MANAGEMENT

15. DIET Whole Protein Restricted Diet Special Metabolic Formula

16. TOO LITTLE TOO MUCH BCAA INTAKE LEUCINE LEUCINE LEUCINE LEUCINE LEUCINE LEUCINE Isoleucine Isoleucine Isoleucine Isoleucine Isoleucine Isoleucine Isoleucine VALINE VALINE VALINE VALINE VALINE VALINE

17. Small amounts of breast milk or standard instant formula Avoid foods high in protein Dietitian will help determine diet routine Your clinic will teach you how to track and limit BCAA

18. Does not contain BCAA Provides necessary nutrients MSUD Anamix ® Early Years DHA for Brain and Eye Development Prebiotics to support immune and digestive health Special Metabolic Formula

19. Laboratory

20. CONCLUSION

21. PREVENTION OF MSUD Genetic Counselling

22. PREVENTION OF MSUD Genetic Testing

23. PREVENTION OF MSUD DNA testing in a foetus before birth

24. REFERENCE Websites https://my.clevelandclinic.org/health/diseases/21168-maple-syrup-urine-disease https://www.epainassist.com/metabolic-disorders/maple-syrup-urine-disease-or-msud https://rarediseases.org/rare-diseases/maple-syrup-urine-disease/#:~:text=Maple%20syrup%20urine%20disease%20(MSUD,and%20valine%2C%20in%20the%20body . YouTube Nutricia Metabolics - https://www.youtube.com/watch?v=DkAVNQBK6uI&t=333s JJ Medicine - https://www.youtube.com/watch?v=MFDPRNNSikw&t=201s

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