Alkaptonuria MCQs With Answer

Alkaptonuria MCQs With Answer offer B. Pharm students a focused review of the biochemical, genetic, and pharmacologic aspects of this rare inborn error of metabolism. This introduction covers homogentisic acid accumulation, HGD gene defects, ochronosis, clinical features such as urine darkening, arthropathy and cardiac involvement, diagnostic tools including urine tests and HPLC, and therapeutic approaches like nitisinone and dietary management. Emphasis on pharmacology, molecular diagnosis, patient counseling, and monitoring prepares pharmacy students for clinical decision-making and exams. Clear, exam-oriented MCQs will reinforce key concepts in biochemistry, genetics, and therapeutics relevant to pharmacy practice. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. What is the primary biochemical defect in alkaptonuria?

• Deficiency of homogentisate 1,2-dioxygenase
• Deficiency of phenylalanine hydroxylase
• Excess tyrosinase activity
• Defect in succinyl-CoA synthetase

Correct Answer: Deficiency of homogentisate 1,2-dioxygenase

Q2. Which metabolite accumulates in alkaptonuria?

• Homogentisic acid
• Homovanillic acid
• Alkaptonic acid
• Protocatechuic acid

Correct Answer: Homogentisic acid

Q3. Alkaptonuria follows which pattern of inheritance?

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

Correct Answer: Autosomal recessive

Q4. Which clinical sign is classically associated with alkaptonuria?

• Darkening of urine on standing
• Hypopigmented skin patches
• Rapid hair greying in infancy
• Excessive sweating

Correct Answer: Darkening of urine on standing

Q5. Ochronosis refers to:

• Deposition of bluish-black pigment in connective tissues
• Inflammation of the ochronary arteries
• Excessive pigment in hair follicles
• Renal deposition of calcium oxalate

Correct Answer: Deposition of bluish-black pigment in connective tissues

Q6. The enzyme homogentisate 1,2-dioxygenase (HGD) normally participates in the degradation of which amino acids?

• Tyrosine and phenylalanine
• Leucine and isoleucine
• Methionine and cysteine
• Tryptophan and histidine

Correct Answer: Tyrosine and phenylalanine

Q7. Which of the following complications is commonly seen in adult patients with alkaptonuria?

• Early-onset degenerative arthritis
• Severe intellectual disability
• Pancreatitis
• Peripheral neuropathy

Correct Answer: Early-onset degenerative arthritis

Q8. Nitisinone acts therapeutically in alkaptonuria by:

• Inhibiting 4-hydroxyphenylpyruvate dioxygenase to reduce HGA production
• Replacing defective HGD enzyme activity
• Binding and removing circulating HGA
• Increasing renal excretion of HGA

Correct Answer: Inhibiting 4-hydroxyphenylpyruvate dioxygenase to reduce HGA production

Q9. A major metabolic side effect of nitisinone therapy is:

• Elevated plasma tyrosine levels
• Hypoglycemia
• Hyperammonemia
• Hyponatremia

Correct Answer: Elevated plasma tyrosine levels

Q10. Which laboratory method is commonly used to quantify homogentisic acid in urine?

• High-performance liquid chromatography (HPLC)
• ELISA for HGD protein
• Complete blood count
• Serum immunofixation electrophoresis

Correct Answer: High-performance liquid chromatography (HPLC)

Q11. At the molecular level, alkaptonuria is caused by mutations in which gene?

• HGD
• PAH
• FAH
• TAT

Correct Answer: HGD

Q12. Which age group typically develops ochronotic arthropathy in alkaptonuria?

• Middle-aged adults (30s–50s)
• Infants under 1 year
• Adolescents (10–19 years)
• Very elderly (>80 years)

Correct Answer: Middle-aged adults (30s–50s)

Q13. Which tissue is characteristically affected by pigment deposition in ochronosis?

• Cartilage and connective tissue
• Hepatocytes
• Pulmonary alveoli
• Skeletal muscle fibers

Correct Answer: Cartilage and connective tissue

Q14. Which cardiovascular complication is associated with long-standing alkaptonuria?

• Aortic valve calcification and stenosis
• Ventricular septal defect
• Hypertrophic cardiomyopathy
• Mitral valve prolapse only

Correct Answer: Aortic valve calcification and stenosis

Q15. Which simple bedside observation may suggest alkaptonuria in a newborn or infant?

• Urine becomes dark on exposure to air
• Blue discoloration of sclera at birth
• Immediate skin hyperpigmentation
• Excessive urine foaming

Correct Answer: Urine becomes dark on exposure to air

Q16. The pigment formed from oxidized homogentisic acid is most similar to:

• Polymeric melanin-like pigment
• Calcium phosphate crystals
• Lipid peroxides
• Glycogen deposits

Correct Answer: Polymeric melanin-like pigment

Q17. Genetic counseling for alkaptonuria should emphasize:

• Autosomal recessive risk and carrier testing
• X-linked carrier risk for mothers only
• Mitochondrial maternal transmission
• No inheritance risk information needed

Correct Answer: Autosomal recessive risk and carrier testing

Q18. Which biochemical test change is expected in the urine of an affected patient?

• High levels of homogentisic acid
• Low urobilinogen levels only
• Absent ketones
• Marked proteinuria as a hallmark

Correct Answer: High levels of homogentisic acid

Q19. Which imaging finding is common in alkaptonuric arthropathy?

• Disc space narrowing and calcification in the spine
• Osteolytic bone lesions like metastases
• Diffuse osteoporosis with no calcification
• Multiple joint effusions without degeneration

Correct Answer: Disc space narrowing and calcification in the spine

Q20. Which of the following is a rationale for dietary therapy in alkaptonuria?

• Restrict phenylalanine and tyrosine to reduce substrate for HGA formation
• High-protein diet to promote HGD expression
• High-tyrosine diet to compete with HGA for excretion
• Low-calorie diet to reduce ochronotic pigment formation

Correct Answer: Restrict phenylalanine and tyrosine to reduce substrate for HGA formation

Q21. Which of the following is a pharmacologic monitoring parameter for patients on nitisinone?

• Plasma tyrosine concentrations
• Serum creatine kinase only
• Random blood glucose frequently
• Serum ammonia routinely

Correct Answer: Plasma tyrosine concentrations

Q22. Which ocular complication can arise from elevated tyrosine due to nitisinone therapy?

• Keratic precipitates/keratopathy from tyrosine crystals
• Retinal detachment
• Optic neuritis
• Conjunctival hemorrhage only

Correct Answer: Keratic precipitates/keratopathy from tyrosine crystals

Q23. Which diagnostic genetic test confirms alkaptonuria?

• Sequencing of the HGD gene to identify pathogenic variants
• Chromosomal karyotype analysis
• MLPA for large deletions in PAH
• Mitochondrial DNA sequencing

Correct Answer: Sequencing of the HGD gene to identify pathogenic variants

Q24. Which of the following best describes the natural history of untreated alkaptonuria?

• Progressive joint and connective tissue degeneration with age
• Sudden neurological deterioration in infancy
• Spontaneous resolution after adolescence
• Rapid renal failure in early childhood

Correct Answer: Progressive joint and connective tissue degeneration with age

Q25. In biochemical pathway terms, homogentisic acid forms from:

• 4-hydroxyphenylpyruvate intermediate of tyrosine catabolism
• Direct oxidation of phenylalanine to HGA
• Degradation of tryptophan
• Ketone body catabolism

Correct Answer: 4-hydroxyphenylpyruvate intermediate of tyrosine catabolism

Q26. Which histopathological feature is seen in ochronotic cartilage?

• Dark pigment deposition in chondrocytes and matrix
• Massive inflammatory infiltrate with neutrophils
• Fatty degeneration of cartilage cells
• Complete absence of proteoglycans only

Correct Answer: Dark pigment deposition in chondrocytes and matrix

Q27. A reliable newborn screening test for alkaptonuria is:

• Not routinely included; diagnosis usually later via urine HGA testing
• Standard heel-prick HGA immunoassay
• Newborn echocardiogram screening
• Universal HGD sequencing at birth

Correct Answer: Not routinely included; diagnosis usually later via urine HGA testing

Q28. Which clinical specialty is often involved for surgical management of alkaptonuric joint disease?

• Orthopedics for joint replacement
• Ophthalmology for joint repair
• Dermatology for cartilage surgery
• Nephrology for joint replacement

Correct Answer: Orthopedics for joint replacement

Q29. Why might alkaptonuria patients develop renal stones?

• Deposition and crystallization of HGA or its complexes in renal tract
• Primary hyperparathyroidism associated with alkaptonuria
• Excessive oxalate absorption unrelated to HGA
• Antibiotic-induced stone formation only

Correct Answer: Deposition and crystallization of HGA or its complexes in renal tract

Q30. Which of the following experimental approaches could directly replace deficient enzyme activity in alkaptonuria?

• Enzyme replacement therapy with HGD (theoretically)
• Beta-lactam antibiotic therapy
• Statin therapy to reduce HGA synthesis
• Calcium channel blockers to prevent pigment deposition

Correct Answer: Enzyme replacement therapy with HGD (theoretically)

Q31. Which biochemical principle explains urine darkening upon alkalinization in alkaptonuria?

• Oxidation and polymerization of homogentisic acid to pigmented compounds
• Precipitation of bilirubin at high pH
• Reduction of urobilinogen under alkaline conditions
• Denaturation of urinary proteins exposing color

Correct Answer: Oxidation and polymerization of homogentisic acid to pigmented compounds

Q32. Which monitoring evaluation is appropriate for long-term management of alkaptonuria patients on therapy?

• Periodic assessment of joint function, cardiac valves, and urine HGA
• Only annual liver biopsy
• Frequent brain MRI scans
• Daily complete blood counts indefinitely

Correct Answer: Periodic assessment of joint function, cardiac valves, and urine HGA

Q33. A pharmacologic interaction concern with nitisinone is:

• Potential inhibition of cytochrome P450 enzymes affecting co-medications
• Complete antagonism of penicillin antibiotics
• Severe hypokalemia when combined with ACE inhibitors
• Marked increase in warfarin metabolism

Correct Answer: Potential inhibition of cytochrome P450 enzymes affecting co-medications

Q34. Which differential diagnosis may present with dark urine but is NOT alkaptonuria?

• Porphyria (e.g., porphobilinogen/porphyrins) on exposure to sunlight
• Type 1 diabetes mellitus with glycosuria
• Hyperthyroidism causing dark urine
• Vitamin C excess causing urine darkening

Correct Answer: Porphyria (e.g., porphobilinogen/porphyrins) on exposure to sunlight

Q35. Which biochemical consequence does accumulated HGA cause in connective tissues?

• Cross-linking and stiffening of collagen leading to degeneration
• Increased collagen synthesis and tissue hypertrophy
• Complete collagen degradation and loss
• Promotion of elastin formation exclusively

Correct Answer: Cross-linking and stiffening of collagen leading to degeneration

Q36. A pharmacist counseling a patient starting nitisinone should advise monitoring for which symptom related to raised tyrosine?

• Visual disturbances or eye irritation
• Excessive hair growth
• Hearing loss
• Persistent cough

Correct Answer: Visual disturbances or eye irritation

Q37. Which assay can be used to screen for HGA in research settings with high sensitivity?

• Gas chromatography–mass spectrometry (GC-MS)
• Standard urine dipstick alone
• Serum protein electrophoresis
• Skin patch testing

Correct Answer: Gas chromatography–mass spectrometry (GC-MS)

Q38. In pharmacotherapy discussions, why is early initiation of nitisinone considered potentially beneficial?

• May reduce long-term HGA accumulation and delay ochronosis/arthropathy
• It immediately reverses existing pigment deposition
• It cures genetic mutations in HGD
• It increases excretion of all aromatic amino acids

Correct Answer: May reduce long-term HGA accumulation and delay ochronosis/arthropathy

Q39. Which laboratory safety consideration is relevant when handling urine samples from patients with alkaptonuria?

• No special infectious precautions beyond standard handling are usually required
• High-level biosafety containment is mandatory
• Samples must be destroyed immediately due to toxicity
• All samples require gamma irradiation before testing

Correct Answer: No special infectious precautions beyond standard handling are usually required

Q40. Which clinical test can help evaluate joint damage severity in alkaptonuria?

• Plain radiography of affected joints and spine
• Skin allergy testing
• Electroencephalography
• Urine culture and sensitivity

Correct Answer: Plain radiography of affected joints and spine

Q41. Which counseling point is important for reproductive-age patients with alkaptonuria?

• Discuss autosomal recessive recurrence risk and carrier testing for partner
• No genetic risk is present for offspring
• Only paternal carriers can transmit the disease
• Pregnancy cures alkaptonuria symptoms permanently

Correct Answer: Discuss autosomal recessive recurrence risk and carrier testing for partner

Q42. Which laboratory finding is NOT typical in alkaptonuria?

• Marked elevation of serum creatine kinase without muscle symptoms
• High urinary homogentisic acid levels
• Normal routine metabolic panels early in disease
• Possible mild renal impairment in advanced disease

Correct Answer: Marked elevation of serum creatine kinase without muscle symptoms

Q43. Which drug class does nitisinone belong to?

• Competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase
• Monoamine oxidase inhibitor
• HMG-CoA reductase inhibitor
• Proteasome inhibitor

Correct Answer: Competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase

Q44. For a suspected case, which simple in-clinic test can suggest presence of HGA in urine?

• Observe urine darkening after standing at room temperature
• Immediate glucose positivity on dipstick
• Presence of nitrites on dipstick
• Strong ketone positivity only

Correct Answer: Observe urine darkening after standing at room temperature

Q45. Which of the following research areas is promising for future alkaptonuria therapies?

• Gene therapy to correct HGD mutations
• Topical ochronosis creams to dissolve pigment
• Systemic antibiotics to break down HGA polymer
• Radiation therapy to remove tissue pigment

Correct Answer: Gene therapy to correct HGD mutations

Q46. Which comorbidity should clinicians be alert for in alkaptonuria patients presenting with back pain?

• Spinal degeneration with possible calcified intervertebral discs
• Autoimmune spondyloarthritis always coexisting
• Spinal infection as the commonest cause
• Primary bone tumors as the typical cause

Correct Answer: Spinal degeneration with possible calcified intervertebral discs

Q47. When considering drug dosing for a patient with alkaptonuria and renal impairment, pharmacists should:

• Adjust dosing based on renal function and drug-specific recommendations
• Ignore renal function since alkaptonuria does not affect kidneys
• Double doses to overcome pigment binding
• Stop all medications permanently

Correct Answer: Adjust dosing based on renal function and drug-specific recommendations

Q48. Which biochemical pathway blockade leads to reduced HGA production when treated with nitisinone?

• Blockade of 4-hydroxyphenylpyruvate conversion to homogentisate
• Blockade of phenylalanine hydroxylation to tyrosine
• Blockade of tyrosine aminotransferase directly
• Blockade of melanin synthesis pathway

Correct Answer: Blockade of 4-hydroxyphenylpyruvate conversion to homogentisate

Q49. Which patient-reported symptom is commonly described in alkaptonuria-related arthropathy?

• Stiffness and chronic pain in weight-bearing joints
• Acute episodic muscle cramps only
• Frequent nosebleeds as the main symptom
• Sensory loss in a glove-and-stocking pattern

Correct Answer: Stiffness and chronic pain in weight-bearing joints

Q50. From a pharmacist’s perspective, what is an important preventive recommendation for patients on nitisinone?

• Regular dietary counseling to limit tyrosine/phenylalanine and ophthalmologic monitoring
• Avoid all dairy products exclusively
• Stop all vitamin supplements permanently
• Increase sun exposure to degrade pigment

Correct Answer: Regular dietary counseling to limit tyrosine/phenylalanine and ophthalmologic monitoring

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com