Metabolic Flashcards
(51 cards)
A 3-day-old neonate presents with poor feeding, vomiting, jaundice, hepatomegaly, and E. coli sepsis. Urinalysis is positive for reducing substances. Which of the following is the most likely diagnosis?
a) Classic galactosemia
b) Hereditary fructose intolerance
c) Glycogen storage disease type I
d) Phenylketonuria
Correct Answer: a
Classic galactosemia is caused by a deficiency of galactose-1-phosphate uridyltransferase (GALT). It typically presents in the neonatal period with jaundice, vomiting, hepatomegaly, failure to thrive, and increased risk of E. coli sepsis. Urine may test positive for reducing substances (e.g., galactose). Hereditary fructose intolerance presents after introduction of fructose. GSD type I (Von Gierke) presents with hypoglycemia and lactic acidosis, not E. coli sepsis. PKU presents later with developmental delay and musty odor.
A 6-month-old infant presents with hepatomegaly, severe fasting hypoglycemia, lactic acidosis, and hyperuricemia. What is the most likely enzyme deficiency?
a) Glucose-6-phosphatase
b) Debranching enzyme
c) Muscle phosphorylase
d) Acid alpha-glucosidase
Correct Answer: a
The features are consistent with Glycogen Storage Disease type I (Von Gierke disease), which is caused by deficiency of glucose-6-phosphatase. This enzyme is crucial for the final step of gluconeogenesis and glycogenolysis, so deficiency results in severe fasting hypoglycemia, lactic acidosis, hepatomegaly, hyperlipidemia, and hyperuricemia. Debranching enzyme deficiency causes GSD III (Cori disease), which is milder. Muscle phosphorylase deficiency causes McArdle disease (GSD V) with exercise intolerance. Acid alpha-glucosidase deficiency causes Pompe disease (GSD II), which presents with hypotonia and cardiomegaly.
A 2-day-old neonate becomes lethargic and develops vomiting after starting protein feeds. Lab results show hyperammonemia with no acidosis or hypoglycemia. What is the most likely diagnosis?
a) Ornithine transcarbamylase (OTC) deficiency
b) Propionic acidemia
c) Maple syrup urine disease
d) Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
Correct Answer: a
OTC deficiency is the most common urea cycle disorder. It is X-linked and typically presents in the neonatal period with vomiting, lethargy, and hyperammonemia after initiation of protein feeds. A key finding is isolated hyperammonemia without metabolic acidosis or hypoglycemia. Propionic acidemia and MSUD present with metabolic acidosis. MCAD deficiency presents with hypoketotic hypoglycemia, not isolated hyperammonemia.
A 4-month-old infant presents with vomiting, poor feeding, hypotonia, and a maple syrup odor of the urine. Which amino acids are most likely elevated in this condition?
a) Phenylalanine, tyrosine, tryptophan
b) Methionine, cysteine, homocysteine
c) Leucine, isoleucine, valine
d) Glycine, serine, alanine
Correct Answer: c
The presentation is classic for Maple Syrup Urine Disease (MSUD), an autosomal recessive disorder caused by deficiency of the branched-chain alpha-ketoacid dehydrogenase complex. It results in accumulation of the branched-chain amino acids (leucine, isoleucine, and valine), which are neurotoxic at high levels. Clinical features include lethargy, poor feeding, neurologic signs, and the characteristic maple syrup odor of the urine. Early diagnosis and dietary restriction are crucial to prevent neurologic damage.
A 5-day-old infant presents with lethargy, vomiting, hypotonia, and metabolic acidosis with ketosis and hyperammonemia. Urine organic acids show elevated methylmalonic acid. What is the most likely diagnosis?
a) Propionic acidemia
b) Methylmalonic acidemia
c) Maple syrup urine disease
d) Phenylketonuria
Correct Answer: b
Methylmalonic acidemia is caused by a defect in methylmalonyl-CoA mutase or vitamin B12 metabolism. It presents in neonates with poor feeding, vomiting, hypotonia, lethargy, metabolic acidosis with ketosis, and hyperammonemia. The hallmark is elevated methylmalonic acid in urine. Propionic acidemia presents similarly but with elevated propionic acid. MSUD shows elevated branched-chain amino acids and no acidosis. PKU typically presents later with intellectual disability and musty body odor.
A 3-year-old child presents with developmental delay, fair skin, eczema, and a musty body odor. Which dietary intervention is most appropriate?
a) Galactose-free diet
b) Low-phenylalanine diet
c) High-protein diet
d) Low-fat diet with medium-chain triglycerides
Correct Answer: b
This child has classic features of phenylketonuria (PKU), caused by phenylalanine hydroxylase deficiency. It leads to elevated phenylalanine and deficiency of tyrosine, which is required for melanin, dopamine, and other neurotransmitters. The hallmark features include intellectual disability, fair skin and hair, eczema, and a musty odor. The mainstay of treatment is a low-phenylalanine diet with tyrosine supplementation, started early to prevent brain damage.
A child with a history of fasting-induced seizures is found to have hypoketotic hypoglycemia. Which of the following enzyme deficiencies is most likely?
a) Glucose-6-phosphatase
b) Medium-chain acyl-CoA dehydrogenase (MCAD)
c) Pyruvate dehydrogenase
d) Propionyl-CoA carboxylase
Correct Answer: b
MCAD deficiency is the most common fatty acid oxidation disorder. It presents with fasting-induced hypoketotic hypoglycemia, vomiting, lethargy, and seizures, often precipitated by illness or prolonged fasting. There is an inability to generate ketone bodies during fasting, a key diagnostic clue. Glucose-6-phosphatase deficiency (Von Gierke disease) leads to lactic acidosis and hyperuricemia. Pyruvate dehydrogenase deficiency causes lactic acidosis. Propionyl-CoA carboxylase deficiency results in propionic acidemia with metabolic acidosis.
A 1-week-old neonate presents with poor feeding, vomiting, hypotonia, and distinctive sweet-smelling urine. Which of the following diagnostic tests is most specific for confirming the diagnosis?
a) Plasma ammonia level
b) Urine reducing substances
c) Tandem mass spectrometry for branched-chain amino acids
d) Blood glucose
Correct Answer: c
The clinical picture suggests Maple Syrup Urine Disease (MSUD), characterized by accumulation of branched-chain amino acids (leucine, isoleucine, and valine). Tandem mass spectrometry is the most specific test, as it allows quantitative detection of these elevated amino acids. Ammonia may be elevated in many inborn errors but is not specific. Urine reducing substances test for galactosemia. Blood glucose may be normal or low but is not diagnostic.
A neonate develops lethargy, vomiting, and metabolic acidosis. Urine organic acids reveal elevated propionic acid. Which of the following enzymes is most likely deficient?
a) Propionyl-CoA carboxylase
b) Methylmalonyl-CoA mutase
c) Carbamoyl phosphate synthetase I
d) Pyruvate carboxylase
Correct Answer: a
Propionic acidemia is caused by a deficiency of propionyl-CoA carboxylase, leading to accumulation of propionic acid. It presents with vomiting, poor feeding, lethargy, hypotonia, and severe metabolic acidosis often with hyperammonemia. Methylmalonyl-CoA mutase deficiency causes methylmalonic acidemia. CPS1 deficiency causes isolated hyperammonemia without acidosis. Pyruvate carboxylase deficiency results in lactic acidosis and hypoglycemia.
A 7-month-old infant presents with hepatomegaly, hypotonia, macroglossia, and hypertrophic cardiomyopathy. Which enzyme deficiency is most likely responsible?
a) Acid alpha-glucosidase
b) Debranching enzyme
c) Glucose-6-phosphatase
d) Muscle phosphorylase
Correct Answer: a
Pompe disease (GSD type II) is caused by acid alpha-glucosidase (acid maltase) deficiency. It is a lysosomal storage disorder characterized by glycogen accumulation within lysosomes. Infants present with hypotonia (‘floppy baby’), macroglossia, hepatomegaly, and hypertrophic cardiomyopathy. Debranching enzyme deficiency causes Cori disease (GSD III). Glucose-6-phosphatase deficiency causes Von Gierke disease (GSD I) with severe hypoglycemia. Muscle phosphorylase deficiency causes McArdle disease (GSD V), which presents later with exercise intolerance.
A 2-year-old presents with developmental delay, self-mutilation behavior, gouty arthritis, and dystonia. What is the most likely diagnosis?
a) Lesch-Nyhan syndrome
b) Tay-Sachs disease
c) Gaucher disease
d) Homocystinuria
Correct Answer: a
Lesch-Nyhan syndrome is caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT). It leads to excess uric acid production, resulting in gout, nephrolithiasis, and neurologic dysfunction. Self-injurious behavior (e.g., lip or finger biting) is pathognomonic. Tay-Sachs presents with neurodegeneration and cherry-red macula but no hyperuricemia. Gaucher disease involves hepatosplenomegaly and bone crises. Homocystinuria presents with marfanoid habitus and thrombosis but not self-mutilation or hyperuricemia.
A neonate presents with lethargy, poor feeding, hypoglycemia, and elevated galactitol in the lens. Which long-term complication is most likely if untreated?
a) Cardiomyopathy
b) Cataracts
c) Hepatocellular carcinoma
d) Sensorineural deafness
Correct Answer: b
The clinical picture is consistent with classic galactosemia, a disorder of galactose metabolism due to GALT enzyme deficiency. Accumulation of galactose leads to its reduction into galactitol, which deposits in the lens causing early cataract formation. Untreated, it can also lead to liver dysfunction and E. coli sepsis. Cardiomyopathy and sensorineural deafness are not hallmark features. Hepatocellular carcinoma is more related to tyrosinemia type I, not galactosemia.
A child presents with hepatomegaly, growth retardation, fasting hypoglycemia, and normal blood lactate levels. Which enzyme is most likely deficient?
a) Glucose-6-phosphatase
b) Debranching enzyme
c) Pyruvate carboxylase
d) Acid alpha-glucosidase
Correct Answer: b
Cori disease (GSD type III) is due to debranching enzyme deficiency, causing accumulation of limit dextrin-type glycogen. It presents with hepatomegaly, mild fasting hypoglycemia, growth retardation, and normal lactate levels. Unlike Von Gierke disease (GSD I), which causes lactic acidosis due to impaired gluconeogenesis, Cori disease has normal lactate levels. Acid alpha-glucosidase deficiency causes Pompe disease, and pyruvate carboxylase deficiency results in lactic acidosis.
A neonate presents with metabolic acidosis, hyperammonemia, and elevated urine orotic acid. Which of the following is the most likely diagnosis?
a) Ornithine transcarbamylase (OTC) deficiency
b) Carbamoyl phosphate synthetase I deficiency
c) Argininemia
d) Citrullinemia
Correct Answer: a
Ornithine transcarbamylase (OTC) deficiency is the most common urea cycle disorder and is X-linked recessive. It presents in neonates with hyperammonemia and elevated urinary orotic acid due to shunting of carbamoyl phosphate into pyrimidine synthesis. In contrast, CPS I deficiency causes hyperammonemia without orotic aciduria. Argininemia and citrullinemia are other urea cycle disorders but typically present later and do not show orotic aciduria to this extent.
A 6-month-old infant with vomiting, failure to thrive, hypotonia, and lens dislocation is diagnosed with a metabolic disorder. Homocystine is elevated in plasma and urine. What is the most appropriate treatment?
a) Methionine supplementation
b) High-protein diet
c) Pyridoxine, folate, and vitamin B12 supplementation
d) Tyrosine-free diet
Correct Answer: c
The clinical and biochemical features suggest homocystinuria, typically due to cystathionine beta-synthase deficiency. Treatment includes pyridoxine (vitamin B6) (cofactor), folate, and vitamin B12, which may reduce homocysteine levels. Some patients respond to pyridoxine alone (B6-responsive type). Methionine should be restricted, not supplemented. Tyrosine-free diet is used in tyrosinemia, not homocystinuria.
A 1-week-old infant has jaundice, hepatomegaly, coagulopathy, and positive reducing substances in urine. Which dietary exclusion is most appropriate?
a) Fructose
b) Galactose
c) Glucose
d) Phenylalanine
Correct Answer: b
This presentation suggests classic galactosemia, caused by GALT deficiency, leading to accumulation of galactose-1-phosphate. Features include jaundice, hepatomegaly, vomiting, E. coli sepsis, and positive reducing substances in urine. Galactose (and therefore lactose) must be excluded from the diet. Fructose exclusion is used in hereditary fructose intolerance. Glucose is a necessary nutrient. Phenylalanine is restricted in phenylketonuria (PKU).
A newborn develops vomiting and lethargy shortly after starting fruit juices. Which metabolic disorder is most likely responsible?
a) Classic galactosemia
b) Hereditary fructose intolerance
c) Fructose-1,6-bisphosphatase deficiency
d) Glycogen storage disease type I
Correct Answer: b
Hereditary fructose intolerance (HFI) is due to a deficiency of aldolase B. Affected infants develop vomiting, lethargy, hypoglycemia, and hepatomegaly shortly after ingesting fructose-containing foods (like fruit juice or baby food). The disorder can be life-threatening if not recognized early. The key to management is strict avoidance of fructose, sucrose, and sorbitol. Galactosemia presents with reducing substances in urine. Fructose-1,6-bisphosphatase deficiency causes hypoglycemia and lactic acidosis. GSD I presents with severe fasting hypoglycemia and hepatomegaly but is not triggered by fruit.
An infant presents with hepatomegaly, severe fasting hypoglycemia, lactic acidosis, and hyperuricemia. Which of the following enzyme deficiencies is responsible?
a) Debranching enzyme
b) Glucose-6-phosphatase
c) Fructose-1-phosphate aldolase
d) Glycogen phosphorylase
Correct Answer: b
Von Gierke disease (Glycogen Storage Disease type I) is caused by a deficiency of glucose-6-phosphatase. It leads to impaired gluconeogenesis and glycogenolysis, resulting in severe fasting hypoglycemia, lactic acidosis, hyperuricemia, and hyperlipidemia. Hepatomegaly is prominent due to glycogen accumulation. Debranching enzyme deficiency causes Cori disease with milder symptoms. Fructose-1-phosphate aldolase deficiency causes hereditary fructose intolerance. Glycogen phosphorylase deficiency is seen in McArdle disease (muscle form).
A 2-year-old child has coarse facial features, hepatosplenomegaly, developmental delay, and corneal clouding. What is the most likely diagnosis?
a) Hurler syndrome
b) Hunter syndrome
c) Gaucher disease
d) Tay-Sachs disease
Correct Answer: a
Hurler syndrome (Mucopolysaccharidosis type I) is an autosomal recessive lysosomal storage disorder caused by α-L-iduronidase deficiency. It presents with coarse facies, hepatosplenomegaly, developmental delay, corneal clouding, and skeletal abnormalities. Hunter syndrome (MPS II) is similar but X-linked and does not have corneal clouding. Gaucher disease involves hepatosplenomegaly and bone crises, but not corneal clouding. Tay-Sachs shows neurodegeneration and cherry-red macula without organomegaly.
A child with hepatomegaly, normal blood glucose, muscle cramps during exercise, and myoglobinuria is diagnosed with a glycogen storage disorder. Which enzyme is most likely deficient?
a) Glucose-6-phosphatase
b) Muscle phosphorylase
c) Debranching enzyme
d) Acid alpha-glucosidase
Correct Answer: b
McArdle disease (GSD type V) is due to a deficiency of muscle glycogen phosphorylase. It presents with exercise intolerance, muscle cramps, and myoglobinuria after strenuous activity. Blood glucose is typically normal because liver metabolism is unaffected. Glucose-6-phosphatase deficiency (GSD I) causes fasting hypoglycemia. Debranching enzyme deficiency (Cori disease) affects both liver and muscle. Acid alpha-glucosidase deficiency causes Pompe disease, which presents with hypotonia and cardiomegaly.
A newborn with vomiting, lethargy, poor feeding, and hyperammonemia has no acidosis and normal anion gap. Which of the following urea cycle disorders is most likely?
a) Propionic acidemia
b) Methylmalonic acidemia
c) Carbamoyl phosphate synthetase I deficiency
d) Isovaleric acidemia
Correct Answer: c
Carbamoyl phosphate synthetase I (CPS1) deficiency is a urea cycle defect that leads to hyperammonemia without acidosis. This helps distinguish it from organic acidemias like propionic, methylmalonic, or isovaleric acidemia, which cause severe metabolic acidosis with an increased anion gap. CPS1 deficiency causes lethargy, vomiting, and encephalopathy due to ammonia toxicity in the absence of acidosis or elevated orotic acid (which is seen in OTC deficiency).
A 5-day-old neonate presents with persistent vomiting, lethargy, poor feeding, and the smell of sweaty feet. What is the most likely diagnosis?
a) Maple syrup urine disease
b) Isovaleric acidemia
c) Tyrosinemia type I
d) Phenylketonuria
Correct Answer: b
Isovaleric acidemia is a disorder of leucine metabolism caused by isovaleryl-CoA dehydrogenase deficiency. It presents in neonates with poor feeding, vomiting, lethargy, and the characteristic ‘sweaty feet’ odor. It can cause metabolic acidosis and neutropenia. Maple syrup urine disease has a sweet, maple syrup-like odor. Tyrosinemia type I presents with liver failure and cabbage-like odor. PKU typically presents later with musty odor and developmental delay.
A neonate develops hypoglycemia, hepatomegaly, jaundice, and a cabbage-like body odor. Which enzyme deficiency is responsible?
a) Fumarylacetoacetate hydrolase
b) Tyrosine aminotransferase
c) Phenylalanine hydroxylase
d) Homogentisate oxidase
Correct Answer: a
Tyrosinemia type I is caused by fumarylacetoacetate hydrolase deficiency and presents in infancy with liver failure, jaundice, hypoglycemia, renal tubular dysfunction, and a cabbage-like odor. Tyrosine aminotransferase deficiency causes type II tyrosinemia with eye and skin findings. Phenylalanine hydroxylase deficiency causes PKU with developmental delay and musty odor. Homogentisate oxidase deficiency causes alkaptonuria with dark urine and ochronosis, typically presenting later in life.
An infant presents with vomiting, irritability, poor feeding, eczema, a musty body odor, and developmental delay. Which metabolic disorder should be suspected?
a) Homocystinuria
b) Phenylketonuria
c) Maple syrup urine disease
d) Isovaleric acidemia
Correct Answer: b
Phenylketonuria (PKU) is caused by phenylalanine hydroxylase deficiency (or tetrahydrobiopterin cofactor defects), leading to accumulation of phenylalanine. It presents with developmental delay, seizures, eczema, musty/mousy body odor, and hypopigmentation. Newborn screening detects it early. Homocystinuria presents with lens dislocation and thromboembolic events. MSUD has a maple syrup smell and presents in the first few days. Isovaleric acidemia presents with a sweaty feet odor.
