Phenylketonuria (PKU) MCQs With Answer

Phenylketonuria (PKU) MCQs With Answer

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Phenylketonuria (PKU) MCQs With Answer

Phenylketonuria (PKU) is an inborn error of metabolism caused by deficient phenylalanine hydroxylase (PAH) activity, leading to accumulation of phenylalanine and neurological toxicity. This concise, exam-focused guide of PKU MCQs with answers helps B. Pharm students master biochemical basis, clinical presentation, newborn screening, dietary management, tetrahydrobiopterin (BH4) responsiveness, pharmacologic options like sapropterin and pegvaliase, and genetic counseling. Questions emphasize enzyme kinetics, diagnostic methods (including tandem mass spectrometry), complications such as intellectual disability and maternal PKU, and up-to-date therapeutic strategies. Designed to reinforce learning and prepare for exams, this set connects molecular mechanisms to pediatric and neonatal pharmacotherapy. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which enzyme deficiency is classically responsible for classical phenylketonuria (PKU)?

  • Tyrosine aminotransferase
  • Phenylalanine hydroxylase
  • Dihydropteridine reductase
  • Homogentisate oxidase

Correct Answer: Phenylalanine hydroxylase

Q2. What is the primary cofactor required by phenylalanine hydroxylase for conversion of phenylalanine to tyrosine?

  • Tetrahydrobiopterin (BH4)
  • NADPH
  • FAD
  • Pyridoxal phosphate (PLP)

Correct Answer: Tetrahydrobiopterin (BH4)

Q3. Which inheritance pattern does PKU typically follow?

  • Autosomal dominant
  • X-linked recessive
  • Autosomal recessive
  • Mitochondrial inheritance

Correct Answer: Autosomal recessive

Q4. Which laboratory screening method is most widely used in modern newborn screening for PKU?

  • Guthrie bacterial inhibition assay
  • Tandem mass spectrometry of dried blood spots
  • Serum tyrosine measurement by colorimetry
  • Urine ferric chloride test

Correct Answer: Tandem mass spectrometry of dried blood spots

Q5. Accumulation of which amino acid causes the neurotoxicity seen in untreated PKU?

  • Tryptophan
  • Tyrosine
  • Phenylalanine
  • Leucine

Correct Answer: Phenylalanine

Q6. Which clinical feature is most characteristic of untreated classical PKU in infancy and childhood?

  • Progressive hyperpigmentation
  • Severe intellectual disability and developmental delay
  • Hypoglycemia unawareness
  • Cardiomyopathy

Correct Answer: Severe intellectual disability and developmental delay

Q7. Why is tyrosine considered conditionally essential in PKU management?

  • PAH converts tyrosine to phenylalanine so tyrosine is depleted
  • Tyr is synthesized from phenylalanine by PAH, which is deficient, so dietary tyrosine is required
  • Tyr is converted to BH4 in PKU patients
  • Tyr inhibits phenylalanine absorption, so supplementation prevents PKU

Correct Answer: Tyr is synthesized from phenylalanine by PAH, which is deficient, so dietary tyrosine is required

Q8. Which compound is a synthetic form of BH4 used to treat BH4-responsive PKU?

  • Sapropterin dihydrochloride
  • Pegvaliase
  • Levodopa
  • Folinic acid

Correct Answer: Sapropterin dihydrochloride

Q9. Pegvaliase is a pharmacologic therapy for PKU that functions primarily by:

  • Inhibiting PAH to reduce phenylalanine production
  • Enzymatic degradation of phenylalanine in plasma
  • Enhancing BH4 synthesis in the liver
  • Blocking intestinal absorption of phenylalanine

Correct Answer: Enzymatic degradation of phenylalanine in plasma

Q10. Which genetic test result would most directly confirm a diagnosis of PKU?

  • Deletion of the PAH gene promoter only
  • Pathogenic homozygous or compound heterozygous mutations in PAH gene
  • Single heterozygous variant in PAH with normal Phe levels
  • Mutation in the tyrosinase gene

Correct Answer: Pathogenic homozygous or compound heterozygous mutations in PAH gene

Q11. Which enzyme deficiency other than PAH can present with hyperphenylalaninemia and may require BH4 loading tests?

  • Dihydropteridine reductase deficiency
  • Ornithine transcarbamylase deficiency
  • Phenylpyruvate decarboxylase deficiency
  • Methylmalonyl-CoA mutase deficiency

Correct Answer: Dihydropteridine reductase deficiency

Q12. In maternal PKU, uncontrolled maternal hyperphenylalaninemia primarily increases risk of which fetal outcome?

  • Neonatal hypothyroidism
  • Congenital heart defects and microcephaly
  • Increased birth weight and macrosomia
  • Renal agenesis

Correct Answer: Congenital heart defects and microcephaly

Q13. Which dietary approach is the cornerstone of long-term management of classical PKU?

  • High-protein diet with BH4 supplementation
  • Low-phenylalanine diet with Phe-restricted medical formula
  • Ketogenic diet to reduce Phe levels
  • High-tyrosine diet without restriction of natural protein

Correct Answer: Low-phenylalanine diet with Phe-restricted medical formula

Q14. Which monitoring parameter is essential during follow-up of patients on PKU therapy?

  • Serum creatinine
  • Plasma phenylalanine concentration
  • Liver enzyme panel monthly
  • Serum calcium

Correct Answer: Plasma phenylalanine concentration

Q15. Which of the following best describes BH4-responsiveness testing in PKU?

  • Administer sapropterin and measure reduction in plasma Phe
  • Measure urinary BH4 excretion after loading with phenylalanine
  • Genotype only and assume all PAH mutations are BH4-responsive
  • Perform an oral glucose tolerance test

Correct Answer: Administer sapropterin and measure reduction in plasma Phe

Q16. Which metabolite is directly increased in urine and plasma and historically detected in PKU?

  • Homogentisic acid
  • Phenylketones such as phenylpyruvate and phenylacetate
  • Propionylcarnitine
  • Alpha-ketoglutarate

Correct Answer: Phenylketones such as phenylpyruvate and phenylacetate

Q17. Which neurochemical deficiency contributes to cognitive impairment in PKU due to impaired tyrosine availability?

  • Serotonin deficiency only
  • Dopamine and norepinephrine deficiency
  • GABA excess leading to sedation
  • Acetylcholine depletion

Correct Answer: Dopamine and norepinephrine deficiency

Q18. Which pharmacokinetic consideration is important when administering pegvaliase therapy?

  • It is an oral small molecule rapidly absorbed
  • It is a pegylated enzyme administered subcutaneously with immunogenicity risk
  • It inhibits hepatic PAH and requires dose reduction in renal impairment
  • It is inhaled and causes bronchospasm in most patients

Correct Answer: It is a pegylated enzyme administered subcutaneously with immunogenicity risk

Q19. Which statement about newborn screening timing for PKU is correct?

  • Screening should be performed immediately at birth (within 1 hour)
  • Optimal screening is at 24–48 hours after birth to allow feeding-related Phe elevation
  • Screening is unnecessary if parents have no history of PKU
  • Screening must wait until the infant is 6 months old

Correct Answer: Optimal screening is at 24–48 hours after birth to allow feeding-related Phe elevation

Q20. Which ratio is useful to differentiate PKU from other causes of elevated phenylalanine?

  • Plasma Phe:Tyrosine ratio
  • Serum methionine:cysteine ratio
  • Urine glucose:ketone ratio
  • Serum BUN:creatinine ratio

Correct Answer: Plasma Phe:Tyrosine ratio

Q21. Which of the following best explains why early dietary treatment improves outcomes in PKU?

  • Dietary restriction prevents accumulation of neurotoxic Phe during critical brain development
  • Diet increases BH4 production naturally
  • High Phe intake boosts catecholamine synthesis
  • Dietary therapy cures the underlying PAH mutation

Correct Answer: Dietary restriction prevents accumulation of neurotoxic Phe during critical brain development

Q22. Which organ is primarily responsible for peripheral metabolism of phenylalanine in PKU therapy using pegvaliase?

  • Liver via hepatic clearance of the enzyme
  • Circulating plasma where pegvaliase degrades Phe
  • Kidneys by excreting unmetabolized Phe unchanged
  • Intestine via luminal enzyme activity only

Correct Answer: Circulating plasma where pegvaliase degrades Phe

Q23. Which adverse effect is commonly associated with sapropterin therapy?

  • Severe neutropenia
  • Headache and gastrointestinal discomfort
  • Progressive renal failure
  • Cardiac arrhythmias

Correct Answer: Headache and gastrointestinal discomfort

Q24. What is the rationale for supplementing tyrosine in the dietary management of PKU?

  • Tyr competes with Phe for transport across the blood-brain barrier, reducing Phe entry
  • Tyr is deficient because PAH normally produces tyrosine from phenylalanine
  • Tyr directly reduces PAH gene expression
  • Tyr increases excretion of phenylketones in urine

Correct Answer: Tyr is deficient because PAH normally produces tyrosine from phenylalanine

Q25. Which population benefit is most directly achieved by implementing universal newborn screening for PKU?

  • Elimination of all genetic diseases
  • Early detection allowing prompt dietary therapy and prevention of intellectual disability
  • Prevention of maternal PKU in future pregnancies
  • Reduction of adult-onset neurodegenerative disease risk

Correct Answer: Early detection allowing prompt dietary therapy and prevention of intellectual disability

Q26. Which laboratory finding suggests classic PKU rather than mild hyperphenylalaninemia?

  • Plasma phenylalanine slightly elevated at 80–200 µmol/L
  • Markedly elevated plasma phenylalanine often >1,200 µmol/L
  • Isolated low tyrosine with normal phenylalanine
  • Elevated homocysteine only

Correct Answer: Markedly elevated plasma phenylalanine often >1,200 µmol/L

Q27. Which clinical test historically used bacterial inhibition to detect elevated phenylalanine?

  • Guthrie test
  • ELISA for Phe
  • Western blot for PAH
  • BAER auditory test

Correct Answer: Guthrie test

Q28. Which counseling topic is crucial for parents of a child diagnosed with PKU?

  • That PKU is contagious and requires isolation
  • Importance of lifelong dietary adherence and genetic recurrence risks
  • That no monitoring is necessary after infancy
  • That vitamin C supplementation cures PKU

Correct Answer: Importance of lifelong dietary adherence and genetic recurrence risks

Q29. Which enzyme cofactor recycling defect can mimic PKU and requires specific therapy with BH4 and neurotransmitter precursors?

  • Tetrahydrobiopterin (BH4) recycling defect due to dihydropteridine reductase deficiency
  • Biopterin oxidase overactivity
  • Methionine synthase deficiency
  • Branched-chain alpha-ketoacid dehydrogenase deficiency

Correct Answer: Tetrahydrobiopterin (BH4) recycling defect due to dihydropteridine reductase deficiency

Q30. Which counseling point is essential for a woman with PKU planning pregnancy?

  • Stop dietary restrictions during pregnancy to support fetal growth
  • Aim for strict metabolic control with target Phe levels prior to and during pregnancy to prevent fetal teratogenicity
  • Replace sapropterin with high-dose vitamin D during pregnancy
  • No special monitoring is required during pregnancy

Correct Answer: Aim for strict metabolic control with target Phe levels prior to and during pregnancy to prevent fetal teratogenicity

Q31. Which neurotransmitter synthesis pathway is directly affected by decreased tyrosine availability in PKU?

  • Serotonin synthesis from tryptophan
  • Catecholamine synthesis from tyrosine (dopamine, norepinephrine)
  • GABA synthesis from glutamate
  • Acetylcholine synthesis from choline

Correct Answer: Catecholamine synthesis from tyrosine (dopamine, norepinephrine)

Q32. Which laboratory technique can quantify multiple amino acids, including phenylalanine, from a single dried blood spot?

  • Thin-layer chromatography
  • Tandem mass spectrometry (MS/MS)
  • Immunohistochemistry
  • Polymerase chain reaction

Correct Answer: Tandem mass spectrometry (MS/MS)

Q33. Which of the following is a potential complication of long-term strict low-protein diets in PKU patients if not properly supplemented?

  • Excessive iron overload
  • Micronutrient deficiencies and poor bone health
  • Hyperammonemia due to protein excess
  • Increased risk of gout

Correct Answer: Micronutrient deficiencies and poor bone health

Q34. Which therapeutic approach directly targets the genetic root of PKU and is currently investigational?

  • Oral BH4 supplementation
  • Enzyme replacement with pegvaliase
  • Gene therapy to restore PAH expression in liver cells
  • Tyrosine supplementation

Correct Answer: Gene therapy to restore PAH expression in liver cells

Q35. Which of these clinical signs may be seen in infants with untreated PKU related to hypopigmentation?

  • Hypertrichosis
  • Hypopigmented skin and fair hair due to melanin synthesis impairment
  • Accelerated nail growth
  • Blue sclerae

Correct Answer: Hypopigmented skin and fair hair due to melanin synthesis impairment

Q36. When assessing a suspected BH4-deficient hyperphenylalaninemia, which additional laboratory evaluation is recommended?

  • Plasma acylcarnitine profile only
  • Neopterin and biopterin levels in urine or blood
  • Serum iron and ferritin
  • Urine organic acids for propionic acid

Correct Answer: Neopterin and biopterin levels in urine or blood

Q37. Which pharmacologic agent is contraindicated or not useful in treating the primary metabolic defect in classical PKU?

  • Sapropterin
  • Pegvaliase
  • High-dose folic acid as monotherapy
  • Dietary Phe restriction

Correct Answer: High-dose folic acid as monotherapy

Q38. Which biophysical mechanism explains reduced cerebral Phe entry when plasma Phe is lowered?

  • Active renal excretion of Phe reduces brain uptake directly
  • Competition at large neutral amino acid (LNAA) transporters at the blood–brain barrier
  • Phe is converted to an inert polymer in plasma
  • Increased melanin binds Phe in the circulation

Correct Answer: Competition at large neutral amino acid (LNAA) transporters at the blood–brain barrier

Q39. Which strategy may be used to help lower brain phenylalanine levels besides systemic Phe reduction?

  • Supplementation with large neutral amino acids (LNAAs) to compete with Phe at the BBB
  • High-dose vitamin B12 to accelerate Phe clearance
  • Oral charcoal to bind Phe in the gut only
  • Frequent carbohydrate loading to dilute Phe concentrations

Correct Answer: Supplementation with large neutral amino acids (LNAAs) to compete with Phe at the BBB

Q40. Which clinical monitoring frequency is typically recommended for plasma Phe in children with PKU on treatment?

  • Once every 5 years
  • Every 1–2 weeks to monthly depending on age and stability
  • Only at transition to adulthood
  • Never if asymptomatic

Correct Answer: Every 1–2 weeks to monthly depending on age and stability

Q41. Which of the following best describes mild hyperphenylalaninemia?

  • Phe levels are normal and no management required
  • Moderately elevated Phe with minimal clinical signs and may require less strict dietary control
  • Phe levels severely elevated >2000 µmol/L with immediate severe symptoms
  • Only elevated tyrosine rather than phenylalanine

Correct Answer: Moderately elevated Phe with minimal clinical signs and may require less strict dietary control

Q42. Which patient education point is important when prescribing sapropterin?

  • Sapropterin cures PKU permanently after a single dose
  • Response varies; a trial is required to determine BH4-responsiveness and dietary adjustments may follow
  • It should be taken with high-phenylalanine meals to enhance effect
  • It is only effective in dihydropteridine reductase deficiency

Correct Answer: Response varies; a trial is required to determine BH4-responsiveness and dietary adjustments may follow

Q43. Which feature distinguishes tetrahydrobiopterin (BH4) deficiency from classical PAH deficiency?

  • BH4 deficiency does not raise phenylalanine levels
  • BH4 deficiency often features neurotransmitter deficiencies and requires additional neurotransmitter precursor therapy
  • BH4 deficiency is X-linked while PAH deficiency is autosomal recessive
  • BH4 deficiency presents only in adulthood

Correct Answer: BH4 deficiency often features neurotransmitter deficiencies and requires additional neurotransmitter precursor therapy

Q44. Which medication requires careful monitoring for hypersensitivity reactions when used in PKU therapy?

  • Sapropterin
  • Pegvaliase
  • Tyramine supplements
  • Vitamin C

Correct Answer: Pegvaliase

Q45. Which dietary component must be limited to manage phenylalanine intake?

  • Carbohydrates
  • Natural protein sources such as meat, dairy, and legumes
  • Dietary fiber
  • Fatty acids

Correct Answer: Natural protein sources such as meat, dairy, and legumes

Q46. Which of the following is an expected biochemical consequence of untreated PKU in brain tissue?

  • Normal myelination
  • Impaired myelination and white matter abnormalities
  • Excessive synthesis of melanin in neurons
  • Increased synaptic pruning leading to enhanced cognition

Correct Answer: Impaired myelination and white matter abnormalities

Q47. Which role do pharmacists commonly play in multidisciplinary PKU care?

  • Only dispensing standard multivitamins
  • Medication counseling, monitoring BH4/pegvaliase therapy, and advising on drug–diet interactions
  • Performing newborn heel-prick screening at birth
  • Providing genetic sequencing in the clinic

Correct Answer: Medication counseling, monitoring BH4/pegvaliase therapy, and advising on drug–diet interactions

Q48. Which statement about long-term outcomes for individuals with PKU managed early and well is correct?

  • Properly treated individuals can achieve near-normal cognitive outcomes and quality of life
  • Dietary therapy has no impact on cognitive outcomes
  • Even with treatment, all patients develop severe intellectual disability
  • PKU always resolves after puberty regardless of treatment

Correct Answer: Properly treated individuals can achieve near-normal cognitive outcomes and quality of life

Q49. Which investigational area holds promise for future definitive treatment of PKU?

  • Chronic antibiotic suppression of gut flora
  • Liver-directed gene editing or gene transfer restoring PAH activity
  • Topical application of BH4 to skin
  • High-dose iron therapy to chelate phenylalanine

Correct Answer: Liver-directed gene editing or gene transfer restoring PAH activity

Q50. Which statement best summarizes a comprehensive PKU management plan for a B. Pharm student to remember?

  • Only give sapropterin and avoid diet; pharmacotherapy alone is sufficient
  • Combine early detection, individualized dietary Phe restriction, regular Phe monitoring, BH4 responsiveness testing, pharmacologic options when appropriate, and lifelong counseling
  • No follow-up is needed after neonatal period
  • Rely solely on genetic testing to guide all treatment decisions without metabolic monitoring

Correct Answer: Combine early detection, individualized dietary Phe restriction, regular Phe monitoring, BH4 responsiveness testing, pharmacologic options when appropriate, and lifelong counseling

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