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ABMGG Medical Biochemical Genetics study materials
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ABMGG Medical Biochemical Genetics practice questions

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Question 1Biochemical Genetics

A newborn presents with hyperammonemia, respiratory alkalosis, and no urinary orotic acid. Which enzyme deficiency is most likely?

  1. Ornithine transcarbamylase deficiency
  2. Carbamoyl phosphate synthetase I deficiency Correct answer.
  3. Argininosuccinate lyase deficiency
  4. N-acetylglutamate synthase deficiency

Explanation

Proximal urea cycle defects (CPS I and NAGS) cause hyperammonemia without orotic aciduria because carbamoyl phosphate does not accumulate and spill into pyrimidine synthesis. OTC and distal defects cause orotic aciduria.

Question 2Biochemical Genetics

Elevated plasma phenylalanine with a normal-to-low tyrosine and normal tetrahydrobiopterin metabolites is most consistent with which disorder?

  1. Phenylketonuria due to phenylalanine hydroxylase deficiency Correct answer.
  2. Tyrosinemia type I
  3. Dihydropteridine reductase deficiency
  4. Maple syrup urine disease

Explanation

PAH deficiency blocks conversion of phenylalanine to tyrosine, so phenylalanine rises while tyrosine is low or normal and biopterin metabolism is intact. Pterin defects would show abnormal biopterin profiles.

Question 3Biochemical Genetics

Which analyte is the primary newborn screening marker for classic galactosemia?

  1. Galactocerebroside
  2. Galactose-1-phosphate uridylyltransferase enzyme activity
  3. Total galactose Correct answer.
  4. Galactitol in urine

Explanation

Newborn screening measures total galactose (or galactose plus GALT enzyme) as the primary marker; enzyme testing is confirmatory. Elevated total galactose flags classic galactosemia before symptoms.

Question 4Biochemical Genetics

A child with developmental delay, coarse facial features, and vacuolated lymphocytes has markedly deficient alpha-L-iduronidase. Which condition is this?

  1. Fabry disease
  2. Hurler syndrome Correct answer.
  3. Hunter syndrome
  4. Morquio syndrome

Explanation

Alpha-L-iduronidase deficiency causes Hurler syndrome (MPS I), a mucopolysaccharidosis with coarse features and vacuolated lymphocytes. Hunter syndrome is iduronate-2-sulfatase deficiency.

Question 5Biochemical Genetics

Which laboratory finding characterizes hereditary fructose intolerance?

  1. Deficiency of fructose-1,6-bisphosphatase
  2. Normal liver function with isolated fructosuria
  3. Deficiency of aldolase B with fructose-induced hypoglycemia Correct answer.
  4. Elevated fructose in urine only

Explanation

Hereditary fructose intolerance is aldolase B deficiency; fructose ingestion causes hypoglycemia, lactic acidosis, and liver dysfunction. Essential fructosuria (fructokinase deficiency) is benign.

Question 6Biochemical Genetics

A patient with homocystinuria due to cystathionine beta-synthase deficiency typically shows which combination of findings?

  1. Low methionine and elevated cystine
  2. Elevated methionine and homocysteine Correct answer.
  3. Elevated cystine with normal homocysteine
  4. Low homocysteine with elevated methionine

Explanation

CBS deficiency blocks homocysteine conversion to cystathionine, so homocysteine accumulates and methionine rises because remethylation is intact. Cystine is typically low.

Question 7Biochemical Genetics

Which enzyme is deficient in classic maple syrup urine disease?

  1. Isovaleryl-CoA dehydrogenase
  2. Methylmalonyl-CoA mutase
  3. Branched-chain alpha-ketoacid dehydrogenase complex Correct answer.
  4. Propionyl-CoA carboxylase

Explanation

MSUD results from deficiency of the branched-chain alpha-ketoacid dehydrogenase complex, causing accumulation of leucine, isoleucine, valine, and their ketoacids. The other enzymes cause different organic acidemias.

Question 8Biochemical Genetics

Cerebrospinal fluid analysis in a neonate shows low 5-methyltetrahydrofolate and low homovanillic acid. Which condition should be suspected?

  1. Cerebral folate deficiency due to FOLR1 defect Correct answer.
  2. Aromatic L-amino acid decarboxylase deficiency
  3. Pyruvate dehydrogenase deficiency
  4. Dihydropteridine reductase deficiency

Explanation

FOLR1 defects impair folate transport into the brain, producing low CSF 5-methyltetrahydrofolate with neurotransmitter metabolite depletion. Serum folate is typically normal.

Question 9Biochemical Genetics

A 3-day-old with poor feeding and hyperammonemia has elevated propionylcarnitine (C3) on acylcarnitine profile. Which diagnosis fits best?

  1. Propionic acidemia Correct answer.
  2. Isovaleric acidemia
  3. Glutaric acidemia type I
  4. Methylmalonic acidemia

Explanation

Elevated C3 acylcarnitine with hyperammonemia in a neonate suggests propionic or methylmalonic acidemia; distinguishing them requires urine organic acids (methylmalonic acid versus 3-hydroxypropionate). Propionic acidemia is characterized by C3 elevation with 3-hydroxypropionic acid.

Question 10Biochemical Genetics

Which metabolite is elevated in the urine of a patient with alkaptonuria?

  1. Orotic acid
  2. Methylmalonic acid
  3. Homogentisic acid Correct answer.
  4. Phenylpyruvic acid

Explanation

Alkaptonuria is homogentisate 1,2-dioxygenase deficiency, causing homogentisic acid accumulation that darkens urine and deposits in cartilage (ochronosis).

Question 11Biochemical Genetics

A patient has elevated very-long-chain fatty acids and a normal plasma acylcarnitine profile. Which test best confirms the suspected diagnosis?

  1. ABCD1 gene sequencing Correct answer.
  2. Urine organic acids
  3. Serum lactate
  4. Plasma amino acids

Explanation

Elevated very-long-chain fatty acids suggest an X-linked adrenoleukodystrophy (ABCD1) peroxisomal disorder. ABCD1 sequencing confirms the diagnosis.

Question 12Biochemical Genetics

A neonate with ambiguous genitalia, hyponatremia, hyperkalemia, and elevated 17-hydroxyprogesterone most likely has which disorder?

  1. 11-beta-hydroxylase deficiency
  2. 3-beta-hydroxysteroid dehydrogenase deficiency
  3. 21-hydroxylase deficiency Correct answer.
  4. 17-alpha-hydroxylase deficiency

Explanation

21-hydroxylase deficiency is the most common congenital adrenal hyperplasia, causing salt-wasting, elevated 17-OHP, and virilization in females. 11-beta-hydroxylase deficiency causes hypertension, not salt wasting.

Question 13Biochemical Genetics

A child with recurrent vomiting, lethargy, and elevated C8-C10 acylcarnitines is at risk for which complication during fasting?

  1. Hyperglycemia
  2. Ketotic hypoglycemia
  3. Hypoketotic hypoglycemia Correct answer.
  4. Hyperammonemia

Explanation

Medium-chain acyl-CoA dehydrogenase deficiency impairs fatty acid oxidation, so fasting produces hypoglycemia with inappropriately low ketones (hypoketotic hypoglycemia).

Question 14Biochemical Genetics

Which finding distinguishes Menkes disease from Wilson disease?

  1. High serum copper in Menkes
  2. Normal copper in Menkes
  3. Elevated urinary copper in Menkes only
  4. Low serum copper and ceruloplasmin in Menkes Correct answer.

Explanation

Menkes disease is an ATP7A defect causing copper malabsorption with low serum copper and ceruloplasmin. Wilson disease (ATP7B) causes copper accumulation with elevated hepatic copper and urinary copper.

Question 15Biochemical Genetics

A patient with episodic ataxia and elevated urinary orotic acid has a defect in which pathway?

  1. Lysosomal degradation
  2. Urea cycle (OTC)
  3. Pyrimidine synthesis (UMPS) Correct answer.
  4. Purine salvage (HGPRT)

Explanation

Hereditary orotic aciduria is UMP synthase (UMPS) deficiency in de novo pyrimidine synthesis, causing orotic aciduria, megaloblastic anemia, and developmental delay.

Question 16Biochemical Genetics

Which test is most appropriate to confirm a suspected diagnosis of cystinuria in a child with recurrent stones?

  1. 24-hour urine cystine excretion Correct answer.
  2. Serum cystine
  3. Urine organic acids
  4. Plasma amino acids

Explanation

Cystinuria is diagnosed by elevated urinary cystine excretion with hexagonal crystals; 24-hour urine cystine quantification is confirmatory. Serum cystine is not diagnostic.

Question 17Biochemical Genetics

A neonate with severe lactic acidosis, elevated pyruvate, and a normal lactate-to-pyruvate ratio most likely has a defect in which process?

  1. Fatty acid beta-oxidation
  2. Mitochondrial respiratory chain complex I
  3. Pyruvate dehydrogenase complex Correct answer.
  4. Pyruvate carboxylase

Explanation

PDH deficiency causes lactic acidosis with elevated pyruvate and a normal or high lactate-to-pyruvate ratio because pyruvate cannot enter the TCA cycle. Respiratory chain defects typically raise the lactate-to-pyruvate ratio.

Question 18Biochemical Genetics

Elevated succinylacetone on newborn screening is pathognomonic for which disorder?

  1. Tyrosinemia type I Correct answer.
  2. Homocystinuria
  3. Phenylketonuria
  4. Tyrosinemia type II

Explanation

Succinylacetone is a specific marker for tyrosinemia type I due to fumarylacetoacetate hydrolase deficiency. It is not elevated in tyrosinemia type II.

Question 19Biochemical Genetics

A patient with a peroxisomal biogenesis disorder (Zellweger spectrum) is expected to show which biochemical pattern?

  1. Isolated hyperammonemia
  2. Elevated very-long-chain fatty acids and low plasmalogens Correct answer.
  3. Elevated acylcarnitines only
  4. Normal VLCFA and elevated plasmalogens

Explanation

Zellweger spectrum disorders impair peroxisome assembly, causing accumulation of VLCFA and reduced plasmalogen synthesis. These two findings together are characteristic.

Question 20Biochemical Genetics

Which enzyme deficiency causes Lesch-Nyhan syndrome?

  1. Hypoxanthine-guanine phosphoribosyltransferase Correct answer.
  2. Adenosine deaminase
  3. Adenylosuccinate lyase
  4. Xanthine oxidase

Explanation

Lesch-Nyhan syndrome is HGPRT deficiency in purine salvage, causing hyperuricemia, self-injury, and neurologic dysfunction. Adenosine deaminase deficiency causes SCID.

Question 21Biochemical Genetics

A patient with a mitochondrial DNA point mutation presents with optic neuropathy and maternal family history. Which feature best supports mtDNA inheritance?

  1. Paternal transmission to all offspring
  2. Autosomal recessive transmission
  3. Maternal transmission with variable heteroplasmy Correct answer.
  4. X-linked dominant transmission

Explanation

mtDNA is maternally inherited, and heteroplasmy explains variable severity among relatives. This pattern distinguishes mitochondrial DNA disorders from nuclear-encoded ones.

Question 22Biochemical Genetics

In a patient with suspected ornithine transcarbamylase deficiency, allopurinol challenge testing is used to demonstrate which finding?

  1. Increased urinary orotidine excretion Correct answer.
  2. Decreased urinary orotidine excretion
  3. Low plasma arginine
  4. Elevated plasma citrulline

Explanation

Allopurinol inhibits pyrimidine degradation, so orotate and orotidine accumulate; in OTC deficiency, carbamoyl phosphate overflow increases orotidine excretion after challenge. This is a provocative test for carrier detection.

Question 23Biochemical Genetics

A patient with elevated plasma methionine, homocysteine, and low cystathionine beta-synthase activity but normal folate is most likely to respond to which treatment?

  1. Dietary phenylalanine restriction
  2. Betaine Correct answer.
  3. Copper supplementation
  4. Nitisinone

Explanation

In CBS deficiency, betaine remethylates homocysteine to methionine via betaine-homocysteine methyltransferase, lowering homocysteine. Pyridoxine is also used, but betaine is the answer among these options.

Question 24Biochemical Genetics

A patient with glutaric acidemia type I is at highest risk for which acute complication during illness?

  1. Striatal injury with acute encephalopathy Correct answer.
  2. Cardiomyopathy with arrhythmia
  3. Renal Fanconi syndrome
  4. Hepatic failure with coagulopathy

Explanation

Glutaric acidemia type I predisposes to acute striatal necrosis during catabolic stress, so emergency sick-day protocols aim to prevent encephalopathy.

Question 25Biochemical Genetics

A patient with elevated urinary xanthine and hypoxanthine but low uric acid most likely has a defect in which enzyme?

  1. Adenosine deaminase
  2. PRPP synthetase
  3. Xanthine oxidase Correct answer.
  4. HGPRT

Explanation

Xanthine oxidase catalyzes the final steps of purine catabolism; its deficiency causes xanthine and hypoxanthine accumulation with low uric acid and xanthine stones.

Question 26Biochemical Genetics

A newborn screening result shows an elevated phenylalanine level with a phenylalanine-to-tyrosine ratio of 3.5. Which additional test is most appropriate to confirm a diagnosis of phenylketonuria?

  1. Serum ammonia measurement
  2. Plasma acylcarnitine profile by tandem mass spectrometry
  3. Quantitative plasma amino acid analysis with biopterin cofactor studies Correct answer.
  4. Urinary organic acid profile by gas chromatography-mass spectrometry

Explanation

Confirming PKU requires quantitative plasma amino acid analysis, and measuring pterin metabolites (biopterin and neopterin) distinguishes PAH deficiency from tetrahydrobiopterin defects. The ratio and phenylalanine level alone do not exclude a cofactor disorder, which changes management.

Question 27Biochemical Genetics

Which biochemical finding is characteristic of galactosemia due to GALT deficiency in an untreated infant?

  1. Elevated urinary homogentisic acid with darkening on standing
  2. Low plasma galactose with elevated galactokinase activity
  3. Elevated erythrocyte galactose-1-phosphate and reduced GALT enzyme activity Correct answer.
  4. Low erythrocyte galactose-1-phosphate with normal GALT activity

Explanation

Classic galactosemia results from deficient galactose-1-phosphate uridylyltransferase, causing accumulation of galactose-1-phosphate in erythrocytes and reduced enzyme activity on direct assay. This is the confirmatory pattern after an abnormal newborn screen.

Question 28Biochemical Genetics

A 4-year-old presents with developmental regression, coarse facial features, and hepatosplenomegaly. Enzyme assay shows deficient beta-galactosidase activity, and the same enzyme is also deficient in cultured fibroblasts. Which additional finding is expected?

  1. Elevated urinary glycosaminoglycans with normal oligosaccharides
  2. Reduced plasma free carnitine with elevated C8 acylcarnitine
  3. Low plasma very-long-chain fatty acids
  4. Elevated urinary keratan sulfate and oligosaccharides Correct answer.

Explanation

GM1 gangliosidosis is caused by beta-galactosidase deficiency and produces accumulation of keratan sulfate and oligosaccharides in urine. The clinical picture of regression, coarse features, and organomegaly fits this lysosomal storage disorder.

Question 29Biochemical Genetics

A child with suspected biotinidase deficiency has a plasma biotin level within the reference range. Which finding best supports the diagnosis?

  1. Elevated plasma very-long-chain fatty acids
  2. Low cerebrospinal fluid glucose with elevated protein
  3. Elevated urinary 3-hydroxyisovaleric acid with abnormal biotinidase enzyme activity Correct answer.
  4. Normal urinary organic acids with elevated plasma lactate

Explanation

Biotinidase deficiency impairs recycling of biotin, so plasma biotin may be normal while tissue carboxylase function is impaired, producing elevated 3-hydroxyisovaleric acid and other organic acids. Confirmation rests on direct measurement of biotinidase enzyme activity.

Question 30Biochemical Genetics

A 6-month-old with hypotonia and cardiomyopathy has a plasma acylcarnitine profile showing elevated C14:1. Which enzyme is most likely deficient?

  1. Short-chain acyl-CoA dehydrogenase
  2. Carnitine palmitoyltransferase II
  3. Very-long-chain acyl-CoA dehydrogenase Correct answer.
  4. Medium-chain acyl-CoA dehydrogenase

Explanation

Elevated C14:1 acylcarnitine is the characteristic marker of very-long-chain acyl-CoA dehydrogenase deficiency, which can present in infancy with hypotonia and cardiomyopathy. Carnitine supplementation and avoidance of fasting are key management steps.

Question 31Biochemical Genetics

A patient with a urea cycle disorder has episodic hyperammonemia. Which laboratory pattern is most consistent with a proximal urea cycle enzyme defect rather than a distal one?

  1. Low blood urea nitrogen with markedly elevated urinary orotic acid
  2. Elevated blood urea nitrogen with low urinary orotic acid
  3. Normal blood urea nitrogen with elevated plasma citrulline
  4. Low blood urea nitrogen with normal urinary orotic acid Correct answer.

Explanation

Proximal defects (carbamoyl phosphate synthetase I and ornithine transcarbamylase) limit carbamoyl phosphate formation or its use before orotate is generated, so urinary orotic acid is not elevated; OTC deficiency is the exception that raises orotate. Low BUN reflects impaired ureagenesis.

Question 32Biochemical Genetics

A neonate with confirmed classic galactosemia is started on a soy-based formula. Which complication remains a risk despite dietary lactose restriction?

  1. Cataract formation within days
  2. Acute liver failure in the first week
  3. Sepsis from Escherichia coli
  4. Speech and motor developmental delay Correct answer.

Explanation

Even with early lactose restriction, many children with classic galactosemia develop long-term speech and motor difficulties, and ovarian insufficiency occurs in females. Cataracts and acute liver failure are largely prevented by prompt dietary treatment.

Question 33Biochemical Genetics

A 10-year-old with developmental delay and behavioral problems has elevated urine glycosaminoglycans, and enzyme testing shows deficient iduronate-2-sulfatase. Which clinical feature is most characteristic of this disorder?

  1. Cherry-red macular spot with normal intelligence
  2. Coarse facial features with a clear cornea
  3. Progressive joint stiffness with corneal clouding Correct answer.
  4. Recurrent hypoglycemia with hepatomegaly

Explanation

Iduronate-2-sulfatase deficiency causes mucopolysaccharidosis type II (Hunter syndrome), which shares multisystem storage features with other mucopolysaccharidoses. Corneal clouding is generally absent in Hunter syndrome, distinguishing it from Hurler syndrome, which does show clouding.

Question 34Biochemical Genetics

A patient with episodic encephalopathy has elevated plasma citrulline and elevated urinary orotic acid after a protein load. Which enzyme deficiency best explains this pattern?

  1. N-acetylglutamate synthase
  2. Ornithine transcarbamylase
  3. Argininosuccinate synthetase Correct answer.
  4. Carbamoyl phosphate synthetase I

Explanation

Argininosuccinate synthetase deficiency (citrullinemia) causes citrulline accumulation, and the excess carbamoyl phosphate is shunted to orotic acid, raising urinary orotate. The combination of high citrulline with high orotate localizes the defect to this step.

Question 35Inborn Errors of Metabolism

A newborn with hyperammonemia has low plasma citrulline, elevated urinary orotic acid, and elevated plasma glutamine. Which enzyme is most likely deficient?

  1. N-acetylglutamate synthase
  2. Carbamoyl phosphate synthetase I
  3. Ornithine transcarbamylase Correct answer.
  4. Argininosuccinate lyase

Explanation

Orotic aciduria with low citrulline points to carbamoyl phosphate accumulation that spills into pyrimidine synthesis, which occurs when ornithine transcarbamylase is deficient. Carbamoyl phosphate synthetase I and N-acetylglutamate synthase defects produce low orotic acid, and argininosuccinate lyase defects raise citrulline.

Question 36Inborn Errors of Metabolism

Which finding is most characteristic of classic galactosemia (GALT deficiency) in an untreated neonate?

  1. Ketonuria with hypoglycemia after fasting
  2. Reducing substances in urine with a normal urine glucose oxidase test Correct answer.
  3. Hyperammonemia with respiratory alkalosis
  4. Conjugated hyperbilirubinemia with acholic stools

Explanation

Galactose excreted in urine is a reducing sugar but is not detected by glucose oxidase, so reducing substances are positive while the glucose-specific test is negative. Untreated infants also develop jaundice, hepatomegaly, and cataracts after galactose exposure.

Question 37Inborn Errors of Metabolism

A child with phenylketonuria has a phenylalanine-restricted diet but develops progressive spasticity and white matter changes despite good metabolic control. Which cofactor disorder should be considered?

  1. Homocystinuria
  2. Maple syrup urine disease
  3. Tyrosinemia type I
  4. Tetrahydrobiopterin deficiency Correct answer.

Explanation

Tetrahydrobiopterin is required for phenylalanine hydroxylase and also for tyrosine and tryptophan hydroxylases, so its deficiency causes neurologic disease even when phenylalanine is controlled. It should be suspected when PKU is accompanied by progressive neurologic findings or low neurotransmitter metabolites.

Question 38Inborn Errors of Metabolism

Which laboratory pattern best fits classic maple syrup urine disease?

  1. Elevated methionine with low homocysteine
  2. Elevated leucine, isoleucine, and valine with elevated alloisoleucine Correct answer.
  3. Elevated citrulline with low arginine
  4. Elevated phenylalanine with normal tyrosine

Explanation

BCKDH deficiency blocks degradation of the branched-chain amino acids, producing elevated leucine, isoleucine, and valine; alloisoleucine is a pathognomonic marker. The disorder presents in the neonatal period with poor feeding and encephalopathy.

Question 39Inborn Errors of Metabolism

A neonate develops liver failure, coagulopathy, and a cabbage-like odor. Urine succinylacetone is elevated. Which enzyme is deficient?

  1. Homogentisate 1,2-dioxygenase
  2. 4-hydroxyphenylpyruvate dioxygenase
  3. Fumarylacetoacetate hydrolase Correct answer.
  4. Tyrosine aminotransferase

Explanation

Tyrosinemia type I is caused by fumarylacetoacetate hydrolase deficiency, which leads to accumulation of succinylacetone, a pathognomonic marker. It causes severe liver disease and is treated with nitisinone plus a tyrosine-restricted diet.

Question 40Inborn Errors of Metabolism

Homocystinuria due to cystathionine beta-synthase deficiency is most commonly associated with which clinical finding?

  1. Corneal clouding
  2. Cherry-red macula
  3. Cataracts
  4. Ectopia lentis Correct answer.

Explanation

Cystathionine beta-synthase deficiency causes elevated homocysteine, leading to connective tissue abnormalities including downward lens dislocation (ectopia lentis), marfanoid habitus, and thrombosis. Early diagnosis and treatment reduce these complications.

Question 41Inborn Errors of Metabolism

An infant presents with seizures, hypotonia, and developmental delay. Plasma very long-chain fatty acids are elevated. Which disorder is most likely?

  1. Multiple carboxylase deficiency
  2. X-linked adrenoleukodystrophy Correct answer.
  3. Medium-chain acyl-CoA dehydrogenase deficiency
  4. Carnitine palmitoyltransferase II deficiency

Explanation

Elevated very long-chain fatty acids indicate a peroxisomal disorder, and X-linked adrenoleukodystrophy is the most common. It can present in childhood with neurologic regression and adrenal insufficiency.

Question 42Inborn Errors of Metabolism

Which is the first-line treatment for acute hyperammonemia in a suspected urea cycle disorder?

  1. Intravenous carnitine
  2. High-protein diet
  3. Intravenous sodium phenylacetate and sodium benzoate with arginine Correct answer.
  4. Oral lactulose

Explanation

Nitrogen scavengers such as sodium phenylacetate and sodium benzoate provide alternative pathways for nitrogen excretion, and arginine supports the urea cycle. Protein intake is temporarily restricted, and dialysis is used if ammonia remains high.

Question 43Inborn Errors of Metabolism

A patient with ornithine transcarbamylase deficiency is being counseled about inheritance. Which statement is correct?

  1. The disorder is maternally inherited through mitochondrial DNA
  2. The disorder is X-linked, so heterozygous females may be affected Correct answer.
  3. The disorder is autosomal dominant with complete penetrance
  4. The disorder is autosomal recessive, so both parents must be carriers

Explanation

Ornithine transcarbamylase deficiency is X-linked, and because of lyonization, heterozygous females can have variable symptoms ranging from asymptomatic to severe. Other urea cycle defects are generally autosomal recessive.

Question 44Inborn Errors of Metabolism

A newborn screening result shows elevated immunoreactive trypsinogen and an elevated phenylalanine level. Which statement about newborn screening is most accurate?

  1. Positive screens require confirmatory testing before a diagnosis is made Correct answer.
  2. Newborn screening detects only treatable disorders
  3. Screening results are unaffected by feeding status
  4. A positive screen establishes the diagnosis and treatment should begin without confirmation

Explanation

Newborn screening identifies infants at increased risk, and all positive results require confirmatory testing. Screening programs also detect some conditions with limited treatment, and feeding status can affect metabolite levels.

Question 45Inborn Errors of Metabolism

A child with recurrent vomiting, lethargy, and hypoglycemia has elevated propionylcarnitine and elevated 3-hydroxypropionate. Which diagnosis is most likely?

  1. Glutaric acidemia type I
  2. Methylmalonic acidemia
  3. Propionic acidemia Correct answer.
  4. Isovaleric acidemia

Explanation

Propionic acidemia results from propionyl-CoA carboxylase deficiency, producing elevated propionylcarnitine (C3) and 3-hydroxypropionate. Methylmalonic acidemia also raises C3 but is distinguished by elevated methylmalonic acid.

Question 46Inborn Errors of Metabolism

Which finding is most consistent with medium-chain acyl-CoA dehydrogenase deficiency during an acute illness?

  1. Hyperammonemia with orotic aciduria
  2. Metabolic alkalosis
  3. Hypoketotic hypoglycemia Correct answer.
  4. Hyperketotic hypoglycemia

Explanation

MCAD deficiency impairs fatty acid oxidation, so during fasting or illness patients develop hypoglycemia with inappropriately low ketones (hypoketotic hypoglycemia). Treatment includes avoiding fasting and providing glucose during illness.

Question 47Inborn Errors of Metabolism

A patient with biotinidase deficiency presents with alopecia, skin rash, and seizures. What is the appropriate treatment?

  1. Oral biotin supplementation Correct answer.
  2. Tetrahydrobiopterin
  3. Nitisinone
  4. Dietary restriction of leucine

Explanation

Biotinidase deficiency is treated with oral biotin, which usually reverses or prevents symptoms if started early. Untreated deficiency can cause neurologic and dermatologic findings.

Question 48Inborn Errors of Metabolism

A child has developmental regression, coarse facial features, and hepatosplenomegaly. Enzyme assay shows deficient beta-galactosidase. Which disorder is most likely?

  1. Gaucher disease
  2. GM1 gangliosidosis Correct answer.
  3. Tay-Sachs disease
  4. Pompe disease

Explanation

GM1 gangliosidosis is caused by beta-galactosidase deficiency and presents with developmental regression, coarse features, and organomegaly. Enzyme testing is diagnostic and genetic testing can confirm.

Question 49Inborn Errors of Metabolism

Which laboratory finding is most characteristic of classical homocystinuria due to cystathionine beta-synthase deficiency?

  1. Normal homocysteine with elevated cystine
  2. Elevated plasma homocysteine with low methionine Correct answer.
  3. Low plasma homocysteine with elevated methionine
  4. Elevated plasma homocysteine with elevated methionine

Explanation

In CBS deficiency, homocysteine cannot be converted to cystathionine, so homocysteine accumulates and methionine is typically low or normal. Treatment includes pyridoxine, betaine, and dietary methionine restriction.

Question 50Inborn Errors of Metabolism

A patient with suspected carnitine palmitoyltransferase II deficiency has recurrent muscle pain and myoglobinuria after exercise. Which additional test is most useful for confirming the diagnosis?

  1. Urine organic acids during a well state only
  2. Plasma very long-chain fatty acids
  3. Acylcarnitine profile before and after exercise or fasting Correct answer.
  4. Serum phenylalanine level

Explanation

CPT II deficiency can be provoked by exercise or fasting, so acylcarnitine profiling under provocative conditions may reveal abnormal long-chain species. Molecular testing of CPT2 can confirm the diagnosis.