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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Rim}}
|QuestionAuthor={{Rim}} (Reviewed by {{YD}})
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Biochemistry
|MainCategory=Biochemistry
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|MainCategory=Biochemistry
|MainCategory=Biochemistry
|SubCategory=General Principles
|SubCategory=General Principles
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|MainCategory=Biochemistry
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|MainCategory=Biochemistry
|MainCategory=Biochemistry
|SubCategory=General Principles
|SubCategory=General Principles
|Prompt=A 7 day old newborn baby is noted to have a seizure episode. The baby was normal at birth but was gradually becoming lethargic and feeding poorly since his fifth day of life. Physical examination of the baby reveals hypotonia in all extremities and a distinctive honey like odor of his diapers. Deficiency of which of the following enzymes is most likely causing the manifestations of this baby?
|Prompt=A 4-day-old newborn is brought to the emergency department (ED) for convulsions. The mother states that her baby is a product of an uneventful vaginal delivery and his neonatal course prior to presentation was normal. She delivered the baby in a rural village abroad and returned to the United States only one day ago. She received all her prenatal vitamins and had regular follow-ups with her obstetrician during pregnancy. In the ED, vital signs are normal, and on physical examination, he appears lethargic and exhibits a stereotyped bicycling movement. The physician notes a distinctive honey-like odor of his diapers. Deficiency of which of the following enzymes is responsible for this patient's condition?
|Explanation=The newborn baby is noted to have [[lethargy]], poor feeding and neurological manifestations of [[hypotonia]] an [[seizure]] during the first week of life. The honey-like characteristic smell of the diapers points out to [[maple syrup urine disease]], an [[autosomal recessive]] disease characterized by the deficiency in branched-chain alpha ketodehydrogenase. Deficiency of this enzyme leads to the elevation of alpha keto acids in the blood due to the impaired breakdown of the branched amino acids [[isoleucine]], [[leucine]] and [[lysine]]. [[Maple syrup disease]] may have a spectrum of clinical presentations that subsequently lead to neurological defects, [[mental retardation]] and [[death]] if left untreated.
|Explanation=Maple syrup urine disease (MSUD) is an autosomal recessive genetic disease characterized by the deficiency of alpha-keto acid dehydrogenase. Patients with MSUD often appear normal at birth. However, plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine) gradually increase, and the disease typically manifests during the 2nd or 3rd day of birth. Manifestations include irritability, poor feeding, convulsions, lethargy, opisthotonus, and a distinctive honey-like/burnt sugar urine odor. Patients may also exhibit stereotyped movements referred to as fencing or bicycling. If left untreated, patients die by the 10th day of birth from ketoacidosis and respiratory failure. The diagnosis of MSUD is confirmed by elevated urinary concentrations of branched-chain amino acid, hydroxyacid, and keto acid. In USA, newborn screening for MSUD is necessary for early treatment and prevention of complications. Management of MSUD involves thiamine supplementation (thiamine is a cofactor for alpha-keto acid dehydrogenase) and dietary restrictions, where patients are advised to avoid foods with branched-chain amino acids.


'''Educational objective:'''
|AnswerA=Acyl-coA dehydrogenase
[[Maple syrup urine disease]] is an [[autosomal recessive]] disease characterized by the deficiency in branched-chain alpha ketodehydrogenase leading to the accumulation of the branched [[amino acid]]s [[leucine]], [[isoleucine]] and [[lysine]] in the [[blood]].
|AnswerAExp=Acyl-coA dehydrogenase is involved in [[fatty acid]] metabolism.
 
'''Reference:'''
First aid for USMLE step 1, 2013. Page 109.
|AnswerA=Acyl-co dehydrogenase
|AnswerAExp=Acyl-co dehydrogenase is involved in the [[fatty acid]] metabolism.  Deficiency in acyl-co A dehydrogenase leads to elevated levels of dicarboxylic acid and decreased levels of [[glucose]] and [[ketone]]s.  The baby's symptoms and signs are characteristic of [[maple syrup disease]] which is caused by the deficiency in branched-chain alpha ketodehydrogenase.
|AnswerB=Lactate dehydrogenase
|AnswerB=Lactate dehydrogenase
|AnswerBExp=The baby's symptoms and signs are characteristic of [[maple syrup disease]] which is caused by the deficiency in branched-chain alpha ketodehydrogenase and not [[lactate dehydrogenase]].
|AnswerBExp=Lactate dehydrogenase catalyzes the conversion from lactate to pyruvate.
|AnswerC=Branched-chain alpha ketodehydrogenase
|AnswerC=Alpha-keto acid dehydrogenase
|AnswerCExp=Branched-chain alpha ketodehydrogenase is involved in the breakdown of branched amino acids such as [[leucine]], [[isoleucine]] and [[lysine]]. Deficiency in branched-chain alpha ketodehydrogenase is the underlying cause of [[maple syrup disease]] of this baby.
|AnswerCExp=Alpha-keto acid dehydrogenase is involved in the breakdown of branched amino acids ([[leucine]], [[isoleucine]] and [[valine]]). MSUD is caused by deficiency of alpha-keto acid dehydrogenase.
|AnswerD=Pyruvate dehydrogenase
|AnswerD=Pyruvate dehydrogenase
|AnswerDExp=Pyruvate dehydrogenase links [[glycolysis]] to [[Krebs cycle]]. Pyruvate dehydrogenase is associated with the accumulation of [[pyruvate]] and [[alanine]] as well as with [[lactic acidosis]].  The baby's symptoms and signs are characteristic of [[maple syrup disease]] which is caused by the deficiency in branched-chain alpha ketodehydrogenase.
|AnswerDExp=Pyruvate dehydrogenase links [[glycolysis]] to [[Krebs cycle]]. Pyruvate dehydrogenase deficiency is associated build-up of [[pyruvate]] and [[alanine]] as well as with [[lactic acidosis]].
|AnswerE=Alpha ketoglutarate dehydrogenase
|AnswerE=Alpha-ketoglutarate dehydrogenase
|AnswerEExp=Alpha ketoglutarate dehydrogenase is involved in [[Krebs cycle]]. The patient's symptoms and signs are characteristic of [[maple syrup disease]] which is caused by the deficiency in branched-chain alpha ketodehydrogenase and not alpha ketoglutarate dehydrogenase.
|AnswerEExp=Alpha ketoglutarate dehydrogenase is involved in [[Krebs cycle]].  
|EducationalObjectives=Maple syrup urine disease (MSUD) is an autosomal recessive genetic disease characterized by the deficiency of alpha-keto acid dehydrogenase. Patients with MSUD often appear normal at birth. However, plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine) gradually increases, and patients initially manifest the disease during the 2nd or 3rd day or birth. The disease typically manifests with irritability, poor feeding, convulsions, lethargy, opisthotonus, and a distinctive honey-like/burnt sugar urine odor. Patients may exhibit stereotyped movements referred to as fencing or bicycling.
 
|References=Strauss KA, Puffenberger EG, Morton DH. Maple Syrup Urine Disease. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2006. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1319/<br>
First Aid 2014 page
|RightAnswer=C
|RightAnswer=C
|WBRKeyword=maple syrup urine disease
|WBRKeyword=Maple syrup urine disease, Enzyme,  Alpha-keto acid dehydrogenase, Autosomal recessive, Ketoacidosis, Convulsions, Newborn screening
|Approved=No
|Approved=Yes
}}
}}

Revision as of 14:39, 11 March 2015
Author [[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Biochemistry
Sub Category SubCategory::General Principles
Prompt [[Prompt::A 4-day-old newborn is brought to the emergency department (ED) for convulsions. The mother states that her baby is a product of an uneventful vaginal delivery and his neonatal course prior to presentation was normal. She delivered the baby in a rural village abroad and returned to the United States only one day ago. She received all her prenatal vitamins and had regular follow-ups with her obstetrician during pregnancy. In the ED, vital signs are normal, and on physical examination, he appears lethargic and exhibits a stereotyped bicycling movement. The physician notes a distinctive honey-like odor of his diapers. Deficiency of which of the following enzymes is responsible for this patient's condition?]]
Answer A AnswerA::Acyl-coA dehydrogenase
Answer A Explanation [[AnswerAExp::Acyl-coA dehydrogenase is involved in fatty acid metabolism.]]
Answer B AnswerB::Lactate dehydrogenase
Answer B Explanation AnswerBExp::Lactate dehydrogenase catalyzes the conversion from lactate to pyruvate.
Answer C AnswerC::Alpha-keto acid dehydrogenase
Answer C Explanation [[AnswerCExp::Alpha-keto acid dehydrogenase is involved in the breakdown of branched amino acids (leucine, isoleucine and valine). MSUD is caused by deficiency of alpha-keto acid dehydrogenase.]]
Answer D AnswerD::Pyruvate dehydrogenase
Answer D Explanation [[AnswerDExp::Pyruvate dehydrogenase links glycolysis to Krebs cycle. Pyruvate dehydrogenase deficiency is associated build-up of pyruvate and alanine as well as with lactic acidosis.]]
Answer E AnswerE::Alpha-ketoglutarate dehydrogenase
Answer E Explanation [[AnswerEExp::Alpha ketoglutarate dehydrogenase is involved in Krebs cycle.]]
Right Answer RightAnswer::C
Explanation [[Explanation::Maple syrup urine disease (MSUD) is an autosomal recessive genetic disease characterized by the deficiency of alpha-keto acid dehydrogenase. Patients with MSUD often appear normal at birth. However, plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine) gradually increase, and the disease typically manifests during the 2nd or 3rd day of birth. Manifestations include irritability, poor feeding, convulsions, lethargy, opisthotonus, and a distinctive honey-like/burnt sugar urine odor. Patients may also exhibit stereotyped movements referred to as fencing or bicycling. If left untreated, patients die by the 10th day of birth from ketoacidosis and respiratory failure. The diagnosis of MSUD is confirmed by elevated urinary concentrations of branched-chain amino acid, hydroxyacid, and keto acid. In USA, newborn screening for MSUD is necessary for early treatment and prevention of complications. Management of MSUD involves thiamine supplementation (thiamine is a cofactor for alpha-keto acid dehydrogenase) and dietary restrictions, where patients are advised to avoid foods with branched-chain amino acids.

Educational Objective: Maple syrup urine disease (MSUD) is an autosomal recessive genetic disease characterized by the deficiency of alpha-keto acid dehydrogenase. Patients with MSUD often appear normal at birth. However, plasma concentrations of branched-chain amino acids (leucine, isoleucine, and valine) gradually increases, and patients initially manifest the disease during the 2nd or 3rd day or birth. The disease typically manifests with irritability, poor feeding, convulsions, lethargy, opisthotonus, and a distinctive honey-like/burnt sugar urine odor. Patients may exhibit stereotyped movements referred to as fencing or bicycling.
References: Strauss KA, Puffenberger EG, Morton DH. Maple Syrup Urine Disease. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2006. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1319/
First Aid 2014 page]]

Approved Approved::Yes
Keyword WBRKeyword::Maple syrup urine disease, WBRKeyword::Enzyme, WBRKeyword::Alpha-keto acid dehydrogenase, WBRKeyword::Autosomal recessive, WBRKeyword::Ketoacidosis, WBRKeyword::Convulsions, WBRKeyword::Newborn screening
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