metabolic disorders 3 Flashcards
Define Medium-Chain Acyl-CoA Dehydrogen Deficiency (MC)
It is a genetic disorder affecting fatty acid metabolism, with a similar frequency to Phenylketonuria (1 in 10,000 induviduals)
How is Medium-Chain Acyl-CoA Dehydrogenase Deficiency inherited?
It is inherited in an autosomal recessive manner.
Describe the biochemical defect in Medium-Chain Acyl-CoA Dehydrogenase Deficiency
It is caused by mutations in medium-chain acyl-CoA dehydrogenase, with about 90% of cases due to a single mutation affecting enzyme stability.
What are some symptoms of Medium-Chain Acyl-CoA Dehydrogenase Deficiency if left untreated?
Symptoms include tiredness, vomiting, sweating, rapid breathing, seizures, and can progress to coma and brain damage.
What are some potential consequences of untreated Medium-Chain Acyl-CoA Dehydrogenase Deficiency?
It can lead to serious and life-threatening problems such as coma, brain damage, and unexpected sudden death.
Describe the importance of early recognition and treatment in Medium-Chain Acyl-CoA Dehydrogenase Deficiency
Early recognition and treatment are crucial as the condition can be life-threatening if not managed promptly.
What is the significance of the K304E mutation in Medium-Chain Acyl-CoA Dehydrogenase Deficiency?
The K304E mutation affects the stability of the enzyme and is responsible for about 90% of MCADD cases.
How does Medium-Chain Acyl-CoA Dehydrogenase Deficiency compare in frequency to Phenylketonuria?
It has a similar frequency to Phenylketonuria, affecting approximately 1 in 10,000 individuals.
Describe the potential symptoms experienced by individuals with Medium-Chain Acyl-CoA Dehydrogenase Deficiency during illness
Symptoms may include tiredness, vomiting, sweating, rapid breathing, and seizures.
What is the risk associated with not being able to eat or tolerate food in individuals with Medium-Chain Acyl-CoA Dehydrogenase Deficiency?
It can lead to serious complications such as coma, brain damage, and even sudden death if not managed appropriately.
How does Medium-Chain Acyl-CoA Dehydrogenase Deficiency affect enzyme stability?
The K304E mutation in MCADD affects the stability of the enzyme, contributing to the biochemical defect.
Describe the potential life-threatening nature of Medium-Chain Acyl-CoA Dehydrogenase Deficiency if not recognized and treated promptly
It can result in serious consequences such as coma, brain damage, and even unexpected sudden death if not managed quickly.
What is the biochemical basis of Medium-Chain Acyl-CoA Dehydrogenase Deficiency?
It is caused by mutations in the medium-chain acyl-CoA dehydrogenase enzyme, with a common mutation affecting enzyme stability.
How does Medium-Chain Acyl-CoA Dehydrogenase Deficiency manifest in individuals who are unwell and unable to eat?
Symptoms may include tiredness, vomiting, sweating, rapid breathing, seizures, and can progress to more severe complications if left untreated.
Describe the potential consequences of untreated Medium-Chain Acyl-CoA Dehydrogenase Deficiency
Untreated MCADD can lead to serious issues like coma, brain damage, and even sudden death.
What are some symptoms that individuals with Medium-Chain Acyl-CoA Dehydrogenase Deficiency may experience if they cannot eat or tolerate food?
Symptoms include tiredness, vomiting, sweating, rapid breathing, seizures, and can escalate to more severe problems if not addressed.
How does the K304E mutation contribute to Medium-Chain Acyl-CoA Dehydrogenase Deficiency?
The K304E mutation affects the stability of the enzyme, playing a significant role in the development of MCADD.
Describe the potential symptoms of Medium-Chain Acyl-CoA Dehydrogenase Deficiency if the condition is not promptly recognized and treated
Symptoms may include tiredness, vomiting, sweating, rapid breathing, seizures, and can lead to more severe complications like coma and brain damage if untreated.
What is the role of the K304E mutation in the biochemical defect of Medium-Chain Acyl-CoA Dehydrogenase Deficiency?
The K304E mutation affects the stability of the enzyme, contributing to the underlying defect in MCADD.
How does Medium-Chain Acyl-CoA Dehydrogenase Deficiency compare in frequency to other metabolic disorders like Phenylketonuria?
It has a similar frequency to Phenylketonuria, affecting approximately 1 in 10,000 individuals.
Describe the potential symptoms individuals with Medium-Chain Acyl-CoA Dehydrogenase Deficiency may experience if they are unwell and unable to eat
Symptoms include tiredness, vomiting, sweating, rapid breathing, seizures, and can lead to more severe complications if not managed appropriately.
What are some potential risks associated with untreated Medium-Chain Acyl-CoA Dehydrogenase Deficiency?
Untreated MCADD can result in serious consequences such as coma, brain damage, and even sudden death if not recognized and treated promptly.
Describe the impact of the K304E mutation on the stability of the enzyme in Medium-Chain Acyl-CoA Dehydrogenase Deficiency
The K304E mutation significantly affects the stability of the enzyme, contributing to the biochemical defect in MCADD.
How does Medium-Chain Acyl-CoA Dehydrogenase Deficiency present in individuals who are ill and unable to consume food?
Symptoms may include tiredness, vomiting, sweating, rapid breathing, seizures, and can progress to more severe complications if not addressed.
Describe the potential outcomes of untreated Medium-Chain Acyl-CoA Dehydrogenase Deficiency
Untreated MCADD can lead to serious complications such as coma, brain damage, and even sudden death if not managed promptly.
What are some symptoms that individuals with Medium-Chain Acyl-CoA Dehydrogenase Deficiency may exhibit if they cannot eat or digest food?
Symptoms include tiredness, vomiting, sweating, rapid breathing, seizures, and can escalate to more severe issues if not addressed.
How does the K304E mutation influence Medium-Chain Acyl-CoA Dehydrogenase Deficiency?
The K304E mutation impacts the stability of the enzyme, playing a crucial role in the development of MCADD.
Describe the potential symptoms of Medium-Chain Acyl-CoA Dehydrogenase Deficiency if not promptly identified and treated
Symptoms may include tiredness, vomiting, sweating, rapid breathing, seizures, and can lead to more severe complications like coma and brain damage if untreated.
What is the function of the K304E mutation in the biochemical defect of Medium-Chain Acyl-CoA Dehydrogenase Deficiency?
The K304E mutation affects the stability of the enzyme, contributing to the underlying defect in MCADD.
Describe Medium-Chain Acyl-CoA Dehydrogen Deficiency (MC)
A condition where mutations interfere with beta-oxidation, preventing the breakdown of fatty acids to acetyl-CoA and their utilization as an energy source.
What is the role of epinephrine and glucagon in the hydrolysis of triacylglycerol?
They stimulate the hydrolysis of triacylglycerol into fatty acids and glycerol.
Define Fatty Acid Oxidation (Beta-oxidation) in mitochondria
A process where each pass removes one acetyl moiety in the form of acetyl-CoA.
How do long-chain fatty acids enter mitochondria?
They cannot freely diffuse across the mitochondrial membrane, so a specific mechanism is necessary for their entry.
Do all acyl-CoA dehydrogenases (ACDHs) catalyze the same chain lengths of fatty acids?
No, there are different isoforms of ACDHs that catalyze very-long-chain, long-chain, medium-chain, and short-chain fatty acids.
Describe the function of the FAD cofactor in Acyl-CoA Dehydrogenase (ACDH) reactions
The FAD cofactor serves as an electron acceptor in the oxidation (dehydrogenation) of acyl-CoA.
How do ACDHs exhibit overlapping substrate specificity?
They share substrates such as ETF, ETF:QO, UQ, and UQH2, with each isoform having specific preferences.
What is the unique substrate for Medium-Chain Acyl-CoA Dehydrogenase (MCAD)?
Octanoyl-CoA is specifically a substrate for MCAD.
Describe the process of Gluconeogenesis
It is the de novo synthesis of glucose in the liver using substrates like amino acids, lactate, and glycerol, but not fatty acids/acetyl-CoA.
What are the products of Ketogenesis?
Ketone bodies such as acetoacetate, beta-hydroxybutyrate, and acetone, which are formed from acetyl-CoA in the liver.
How are ketone bodies generated in the absence of liver function?
Ketone bodies are not produced in the liver, but in other tissues, they are converted back to acetyl-CoA for energy production.
Define Ketogenesis
The process of generating ketone bodies like acetoacetate, beta-hydroxybutyrate, and acetone from acetyl-CoA, primarily occurring in the liver.
Describe the formation of ne (exhaled) in the body.
Formed from acetyl-CoA generated by β-oxidation in the liver, enters circulation to extrahepatic tissues, and is converted back to acetyl-CoA which enters the citric acid cycle.
What are the consequences if children and babies cannot mount a ketotic response during fasting?
Severe consequences due to the need to rapidly mount a ketotic response, especially in the context of impaired fatty acid oxidation.
Define MCADD and explain its impact during fasting.
MCAD deficiency leads to low acetyl-CoA levels due to defective β-oxidation, reduced formation of ketone bodies, and worsened hypoglycemia during fasting.
How does MCADD typically present in young children?
Young children with MCADD often present with intermittent hypoglycemia/vomiting induced by minor infections, inability to mount a ketotic response to fasting, and characteristic patterns of acyl-carnitine esters in blood/urine.
What is the recommended treatment for MCADD?
Avoid fasting, follow a high carbohydrate/low fat diet, avoid medium-chain triglycerides, supplement with carnitine, and be vigilant for signs during metabolic stress like vomiting/diarrhea or prolonged fasting.
Describe a case of MCAD deficiency in a 16-year-old girl.
The 16-year-old girl had her first presentation of MCAD deficiency following an alcoholic binge and subsequent period of starvation, leading to acute encephalopathy progressing to coma.
Describe the management of renal, cardiac, and hepatic in the provided content.
Managed with intensive supportive care including mechanical ventilation, inotropic support, blood products, and renal replacement therapy.
What was the diagnosis confirmed on day 6 in the content?
MCAD deficiency.
How does alcohol consumption affect gluconeogenesis according to the content?
It inhibits gluconeogenesis by accumulating NADH, which inhibits the lactate to pyruvate reaction.
Define MCADD pathophysiology as mentioned in the content.
It is characterized by dicarboxylic aciduria.
What therapy is recommended for MCAD Deficiency according to the content?
Carnitine therapy.
What is elevated octanoylcarnitine diagnostic of in MCAD deficiency?
MCAD deficiency.
How is MCADD screening test conducted according to the content?
Blood from a “Guthrie” heel prick test is used for acyl-carnitine analysis.
Define the purpose of derivatization as butyl esters in acyl-carnitine analysis.
It allows amino acid analysis on the same sample preparation and has been validated for newborn screening of various disorders like phenylketonuria.
What does the elevation of C8 (octanoyl carnitine) indicate in MCADD detection?
MCADD C8 elevated, along with C6 and C10, with internal standards (2H3).
Describe the consequences of CTP II deficiency as mentioned in the content.
Long-chain acylcarnitines cannot enter the matrix, leading to the accumulation of C16+.
What is the consequence of MAD deficiency according to the content?
It causes “multiple acylcarnitine dehydrogenase deficiency” leading to Glutaric acidemia type II.
How are many other defects in fatty acid metabolism easily detected according to the content?
They are easily detected by acyl-carnitine profile in MS/MS analysis.
Define the bottleneck in mitochondrial metabolism caused by VLCAD deficiency as per the content.
It leads to the accumulation of C14-C18 acylcarnitines.
What is the defect in electron transfer proteins that causes consequences similar to other fatty acid metabolism defects?
CTP II deficiency.
Describe the accumulation pattern of acylcarnitines in MAD deficiency according to the content.
It leads to the accumulation of all acylcarnitines.
What does the fragment with m/z 85 confirm in MS/MS analysis of acylcarnitines according to the content?
It confirms that the precursor ion was an acylcarnitine.
How is the diagnosis of MCAD deficiency confirmed through MS/MS analysis?
By detecting elevated octanoylcarnitine and other specific acylcarnitines.
Define the role of collision-induced dissociation in MS/MS analysis of acylcarnitines.
It causes fragmentation of molecules to confirm the presence of specific fragments like m/z 85.
What is the significance of elevated carnitine in plasma from oral supplements in MCAD deficiency?
It indicates the use of carnitine therapy in managing the deficiency.
Describe the process of avoiding dicarboxylic acid formation in MCAD deficiency.
By restoring
How is the MCADD screening test conducted using blood samples according to the content?
It involves analyzing acylcarnitines in blood samples obtained from a “Guthrie” heel prick test.
What is the purpose of using internal standards (2H3) in MCADD detection?
To aid in the accurate identification of specific acylcarnitines like C8, C6, and C10.
Define the role of CPTII/translocase in MCAD deficiency when [Acyl-CoA]/[CoASH] is high.
It works in reverse to restore
Describe the process of diagnosing MCAD deficiency through acyl-carnitine analysis in MS/MS.
By detecting elevated levels of specific acylcarnitines like octanoylcarnitine.
What is the significance of elevated octanoylcarnitine in MCAD deficiency diagnosis?
It is a key marker indicating the presence of MCAD deficiency.
How does VLCAD deficiency lead to the accumulation of C14-C18 acylcarnitines?
Due to the inability of these acylcarnitines to enter the mitochondrial matrix.
Define the role of collision-induced dissociation in confirming the presence of acylcarnitines in MS/MS analysis.
It causes fragmentation of molecules to produce specific fragments like m/z 85, confirming the presence of acylcarnitines.
Describe the process of diagnosing MAD deficiency through acyl-carnitine analysis in MS/MS.
By detecting the accumulation of all acylcarnitines as a characteristic feature of the deficiency.
What is the consequence of MAD deficiency in mitochondrial metabolism according to the content?
It essentially causes a “bottleneck” in mitochondrial metabolism due to defects in electron transfer proteins.
How are the consequences of CTP II deficiency similar to other fatty acid metabolism defects?
They lead to the accumulation of specific acylcarnitines due to the inability of certain acylcarnitines to enter the mitochondrial matrix.
Define the purpose of derivatization as butyl esters in acyl-carnitine analysis according to the content.
It allows for amino acid analysis on the same sample preparation and is validated for newborn screening of various disorders like phenylketonuria.
Describe the process of avoiding the formation of dicarboxylic acids in MCAD deficiency.
By restoring the balance of
What is the significance of elevated carnitine levels in plasma from oral supplements in managing MCAD deficiency?
It indicates the use of carnitine therapy to address the deficiency.
How is the MCADD screening test conducted using blood samples as described in the content?
It involves analyzing acylcarnitines in blood samples obtained from a “Guthrie” heel prick test.
What is the role of derivatization as butyl esters in acyl-carnitine analysis according to the content?
It enables amino acid analysis on the same sample preparation and is validated for newborn screening of various disorders.
Describe the process of diagnosing MCAD deficiency through acyl-carnitine analysis in MS/MS as outlined in the content.
By identifying elevated levels of specific acylcarnitines like octanoylcarnitine.
What does the elevation of octanoylcarnitine indicate in the diagnosis of MCADD according to the content?
It is a key marker indicating the presence of MCAD deficiency.
Define the role of CPTII/translocase in MCAD deficiency when [Acyl-CoA]/[CoASH] levels are high.
It operates in reverse to restore the balance of
Describe the process of diagnosing MCAD deficiency through MS/MS analysis as per the content.
By detecting elevated levels of specific acylcarnitines like octanoylcarnitine.
What is the significance of elevated octanoylcarnitine in the diagnosis of MCAD deficiency?
It serves as a crucial indicator of the presence of MCAD deficiency.
How does VLCAD deficiency lead to the accumulation of C14-C18 acylcarnitines according to the content?
Due to the inability of these acylcarnitines to enter the mitochondrial matrix.
Describe the process of diagnosing MAD deficiency through acyl-carnitine analysis in MS/MS as per the content.
By detecting the accumulation of all acylcarnitines as a characteristic feature of the deficiency.
