A 5-month-old boy is admitted to a Mumbai hospital with his third pneumonia, chronic diarrhoea and persistent oral thrush. Chest X-ray shows no thymic shadow and cupping of the costochondral junctions. Absolute lymphocyte count is 300/µL, with very low T, B and NK cells. Accumulation of which metabolite is directly toxic to his lymphocytes?

Deoxyadenosine triphosphate (dATP)

Deoxyguanosine triphosphate (dGTP)

A 55-year-old businessman from Surat wakes at night with a hot, red, very painful swollen right great toe the day after a wedding feast with alcohol. The joint is aspirated in casualty and examined under polarised light. Which finding confirms the likely diagnosis?

Urate crystals with negative birefringence

Pyrophosphate crystals with positive birefringence

Pyrophosphate crystals with negative birefringence

Urate crystals with positive birefringence

A 30-year-old man from Thrissur has had two episodes of renal colic. The stones were radiolucent on X-ray, and urine microscopy shows round, reddish-brown crystals with a dark outline and central Maltese-cross pattern under polarised light. Stone analysis by infrared spectroscopy identifies 2,8-dihydroxyadenine. Which enzyme is deficient?

Adenine phosphoribosyltransferase

Hypoxanthine-guanine phosphoribosyltransferase

A 6-day-old boy, born at term to consanguineous parents in Srinagar, has had seizures since day 2 that do not respond to phenobarbital, levetiracetam or pyridoxine. He feeds poorly and is hypertonic with an exaggerated startle. MRI shows changes resembling hypoxic injury, although Apgar scores were normal. Serum uric acid is 0.4 mg/dL (reference 2.0-5.5 mg/dL), urine sulphite dipstick is positive, and urine xanthine is raised. What is the most likely diagnosis?

Purine nucleoside phosphorylase deficiency

Isolated xanthine oxidase deficiency

A 20-year-old man in a Kolkata OPD has had two attacks of gout and passed a uric acid stone. He has normal intelligence and no abnormal movements. His uncle had similar problems. HGPRT activity in his red cells is about 10% of normal. Why does he overproduce uric acid?

Unused PRPP drives de novo purine synthesis

Renal tubular urate secretion is reduced

Xanthine oxidase is induced in the liver

Muscle ATP breakdown is greatly increased

Nucleotide metabolism, gout and purine disorders

16 NEET-PG practice questions on Nucleotide metabolism, gout and purine disorders, part of Biochemistry. The first 16 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Medium
A 5-month-old boy is admitted to a Mumbai hospital with his third pneumonia, chronic diarrhoea and persistent oral thrush. Chest X-ray shows no thymic shadow and cupping of the costochondral junctions. Absolute lymphocyte count is 300/µL, with very low T, B and NK cells. Accumulation of which metabolite is directly toxic to his lymphocytes?
1. AUric acid
2. BDeoxyguanosine triphosphate (dGTP)
3. CDeoxyadenosine triphosphate (dATP)
4. DOrotic acid
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Answer: C · Deoxyadenosine triphosphate (dATP)
Severe combined immunodeficiency with absent T, B and NK cells and bony changes at the costochondral junctions points to adenosine deaminase deficiency. ADA normally deaminates adenosine and deoxyadenosine; without it deoxyadenosine is phosphorylated to dATP, which inhibits ribonucleotide reductase and blocks DNA synthesis in dividing lymphocytes, which have high kinase activity. Deoxyadenosine also inactivates S-adenosylhomocysteine hydrolase. Live vaccines such as BCG and oral polio must be withheld, and only irradiated blood products are given.
- A: Uric acid is the end product of purine breakdown and does not kill lymphocytes.
- B: dGTP accumulates in purine nucleoside phosphorylase deficiency, which spares B cells largely.
- D: Orotic acid accumulates in pyrimidine and urea cycle defects, not in SCID.
Question 2 · Easy
A 55-year-old businessman from Surat wakes at night with a hot, red, very painful swollen right great toe the day after a wedding feast with alcohol. The joint is aspirated in casualty and examined under polarised light. Which finding confirms the likely diagnosis?
1. APyrophosphate crystals with positive birefringence
2. BUrate crystals with negative birefringence
3. CPyrophosphate crystals with negative birefringence
4. DUrate crystals with positive birefringence
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Answer: B · Urate crystals with negative birefringence
Acute gout of the first metatarsophalangeal joint (podagra) after a purine-rich meal and alcohol is caused by monosodium urate crystals. Under compensated polarised light they are needle-shaped and strongly negatively birefringent, appearing yellow when parallel to the axis of the compensator. Calcium pyrophosphate crystals of pseudogout are rhomboid and weakly positively birefringent, and usually affect the knee or wrist of older people. Alcohol raises urate both by increasing purine turnover and, through lactate, by reducing urate excretion.
- A: Positively birefringent rhomboid calcium pyrophosphate crystals mean pseudogout.
- C: Calcium pyrophosphate crystals are weakly positively birefringent.
- D: Urate crystals are negatively, not positively, birefringent.
Question 3 · Medium
A 30-year-old man from Thrissur has had two episodes of renal colic. The stones were radiolucent on X-ray, and urine microscopy shows round, reddish-brown crystals with a dark outline and central Maltese-cross pattern under polarised light. Stone analysis by infrared spectroscopy identifies 2,8-dihydroxyadenine. Which enzyme is deficient?
1. AHypoxanthine-guanine phosphoribosyltransferase
2. BXanthine oxidase
3. CAdenosine deaminase
4. DAdenine phosphoribosyltransferase
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Answer: D · Adenine phosphoribosyltransferase
Adenine phosphoribosyltransferase normally salvages adenine to AMP. When it is missing, adenine is oxidised by xanthine oxidase to 2,8-dihydroxyadenine, which is very insoluble at any urine pH and forms radiolucent stones and crystal nephropathy that can lead to chronic kidney disease. These stones are easily mistaken for uric acid stones unless analysed by infrared spectroscopy. Treatment is allopurinol or febuxostat, which block the conversion, with a high fluid intake; urine alkalinisation does not help.
- A: HGPRT deficiency raises uric acid and causes Lesch-Nyhan or Kelley-Seegmiller syndrome.
- B: Xanthine oxidase deficiency causes xanthine stones and a very low serum uric acid.
- C: ADA deficiency causes severe combined immunodeficiency, not stones.
Question 4 · Hard
A 6-day-old boy, born at term to consanguineous parents in Srinagar, has had seizures since day 2 that do not respond to phenobarbital, levetiracetam or pyridoxine. He feeds poorly and is hypertonic with an exaggerated startle. MRI shows changes resembling hypoxic injury, although Apgar scores were normal. Serum uric acid is 0.4 mg/dL (reference 2.0-5.5 mg/dL), urine sulphite dipstick is positive, and urine xanthine is raised. What is the most likely diagnosis?
1. APyridoxine-dependent epilepsy
2. BPurine nucleoside phosphorylase deficiency
3. CIsolated xanthine oxidase deficiency
4. DMolybdenum cofactor deficiency
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Answer: D · Molybdenum cofactor deficiency
Molybdenum cofactor is needed by xanthine oxidase (dehydrogenase), sulphite oxidase and aldehyde oxidase. When it is missing, sulphite accumulates and damages the brain, causing intractable neonatal seizures and an MRI picture that mimics hypoxic-ischaemic encephalopathy, while loss of xanthine oxidase activity lowers uric acid and raises xanthine. The combination of very low uric acid with a positive sulphite test points to it rather than to a single enzyme defect. Type A disease can be treated with cyclic pyranopterin monophosphate (fosdenopterin) if started early.
- A: Pyridoxine-dependent epilepsy responds to pyridoxine and does not lower uric acid.
- B: PNP deficiency lowers uric acid but presents with T-cell immunodeficiency, not neonatal sulphite toxicity.
- C: Isolated xanthine oxidase deficiency lowers uric acid but does not cause sulphite toxicity or seizures.
Question 5 · Medium
A 20-year-old man in a Kolkata OPD has had two attacks of gout and passed a uric acid stone. He has normal intelligence and no abnormal movements. His uncle had similar problems. HGPRT activity in his red cells is about 10% of normal. Why does he overproduce uric acid?
1. ARenal tubular urate secretion is reduced
2. BUnused PRPP drives de novo purine synthesis
3. CXanthine oxidase is induced in the liver
4. DMuscle ATP breakdown is greatly increased
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Answer: B · Unused PRPP drives de novo purine synthesis
Partial HGPRT deficiency (Kelley-Seegmiller syndrome) causes early-onset gout and urate stones without the severe neurological features of Lesch-Nyhan syndrome. Less PRPP is used for salvage, so PRPP accumulates and stimulates glutamine PRPP amidotransferase, the committed step of de novo purine synthesis. Hypoxanthine and guanine that cannot be salvaged are also degraded to uric acid. Allopurinol reduces urate production, with high fluid intake to prevent stones.
- A: Reduced excretion is the usual mechanism in primary gout, but this patient has an enzyme defect causing overproduction.
- C: Xanthine oxidase is not induced; more substrate reaches it.
- D: Increased ATP breakdown occurs in exercise or glycogen storage disease, not in HGPRT deficiency.
Question 6 · Easy
Parents in Patna bring their 2-year-old son, who cannot yet sit without support, has twisting dystonic postures and chews his lower lip and fingertips into raw wounds although it clearly hurts him. Orange grit has stained his nappies since early infancy. Serum uric acid is 11 mg/dL. Which enzyme is deficient?
1. AHypoxanthine-guanine phosphoribosyltransferase
2. BXanthine oxidase
3. CPRPP synthetase
4. DAdenine phosphoribosyltransferase
Answer and explanation in LearnFree account
Question 7 · Medium
A 34-year-old woman with rheumatoid arthritis has been well controlled on leflunomide for two years at a rheumatology clinic in Pune. She now wants to become pregnant. Which step of nucleotide synthesis does her drug block?
1. APRPP amidotransferase in purine synthesis
2. BIMP dehydrogenase in guanine nucleotide synthesis
3. CDihydroorotate dehydrogenase in pyrimidine synthesis
4. DThymidylate synthase in dTMP synthesis
Answer and explanation in LearnFree account
Question 8 · Medium
A 10-year-old girl from Bhubaneswar has lifelong mild jaundice, splenomegaly and anaemia (Hb 9.2 g/dL, reticulocytes 9%). The direct Coombs test is negative, osmotic fragility and G6PD are normal, and the smear shows prominent coarse basophilic stippling. Blood lead is normal. Which enzyme deficiency best explains her haemolysis?
1. AGlucose phosphate isomerase
2. BPyruvate kinase
3. CGlucose-6-phosphate dehydrogenase
4. DPyrimidine 5'-nucleotidase
Answer and explanation in LearnFree account
Question 9 · Medium
A 56-year-old man of Han Chinese descent working in Kolkata has recurrent gout with tophi. Before starting urate-lowering therapy he tests positive for HLA-B*58:01, so his physician avoids allopurinol and prescribes febuxostat. How does febuxostat lower serum uric acid?
1. AConversion of uric acid to allantoin
2. BBlocking renal urate reabsorption by URAT1
3. CNon-purine inhibition of xanthine oxidase
4. DInhibition of PRPP amidotransferase
Answer and explanation in LearnFree account
Question 10 · Medium
A 3-year-old boy with Lesch-Nyhan syndrome is started on allopurinol by the paediatric team in Jaipur. While counselling the parents, the resident checks four statements: 1. The disorder is inherited as an X-linked recessive trait. 2. Allopurinol will help prevent urate stones, nephropathy and gout. 3. Allopurinol will reverse his self-injurious behaviour. 4. He cannot salvage hypoxanthine and guanine. Which statements are correct?
1. A1 and 4 only
2. B1, 2 and 3 only
3. C1, 3 and 4 only
4. D1, 2 and 4 only
Answer and explanation in LearnFree account
Question 11 · Medium
An 18-month-old boy has megaloblastic anaemia that did not respond to B12 and folic acid, poor growth and crystalluria. The paediatric registrar suspects hereditary orotic aciduria and lists four points: 1. The defect is in UMP synthase. 2. Plasma ammonia is typically raised. 3. Oral uridine bypasses the block and lowers orotic acid output. 4. It is distinguished from ornithine transcarbamoylase deficiency by a normal ammonia. Which points are correct?
1. A1, 3 and 4 only
2. B1, 2 and 4 only
3. C1, 2 and 3 only
4. D1 and 3 only
Answer and explanation in LearnFree account
Question 12 · Easy
A 1-year-old girl is referred to a paediatric haematology clinic with failure to thrive and megaloblastic anaemia that has not improved after two months of vitamin B12 and folic acid. Serum B12 and folate are normal, ammonia is normal, and the urine contains needle-shaped crystals of orotic acid. What is the treatment of choice?
1. ASodium benzoate
2. BFolinic acid
3. CHydroxocobalamin injections
4. DOral uridine
Answer and explanation in LearnFree account
Question 13 · Hard
A 4-month-old boy in a Bengaluru hospital has severe combined immunodeficiency from adenosine deaminase deficiency, confirmed by absent red cell ADA activity. He received BCG at birth and now has an ulcer at the vaccination site with enlarged left axillary nodes that show acid-fast bacilli. His 5-year-old sister is a full HLA match. After starting antitubercular treatment, what is the definitive treatment for his immunodeficiency?
1. ALifelong intravenous immunoglobulin alone
2. BHLA-matched sibling stem cell transplant
3. CThymus tissue transplantation
4. DPEG-ADA enzyme replacement alone
Answer and explanation in LearnFree account
Question 14 · Medium
A 15-year-old boy with glycogen storage disease type I (doll-like face, large liver, fasting hypoglycaemia and lactic acidosis) is seen in a Vellore clinic with a painful swollen ankle. Serum uric acid is 10.5 mg/dL. Which mechanism contributes to his hyperuricaemia?
1. ADeficient HGPRT activity in the liver
2. BIncreased absorption of dietary purines
3. CLactate competing for renal urate excretion
4. DReduced conversion of urate to allantoin
Answer and explanation in LearnFree account
Question 15 · Medium
A 35-year-old woman who received a kidney transplant in Ahmedabad is maintained on tacrolimus, prednisolone and mycophenolate mofetil. Mycophenolate acts mainly on lymphocytes because they depend on de novo purine synthesis. Which enzyme does it inhibit?
1. AIMP dehydrogenase
2. BDihydroorotate dehydrogenase
3. CDihydrofolate reductase
4. DRibonucleotide reductase
Answer and explanation in LearnFree account
Question 16 · Hard
A 3-year-old girl from Kanpur has had recurrent chest infections, chickenpox that lasted three weeks, and now an unsteady gait and spasticity of the legs. She also has autoimmune haemolytic anaemia. Absolute lymphocyte count is 400/µL; CD3 T cells are markedly low while B cells are nearly normal and immunoglobulins are present. Serum uric acid is 0.8 mg/dL (reference 2.5-5.5 mg/dL). Which enzyme is most likely deficient?
1. APurine nucleoside phosphorylase
2. BXanthine oxidase
3. CAdenosine deaminase
4. DHypoxanthine-guanine phosphoribosyltransferase
Answer and explanation in LearnFree account

Nucleotide metabolism, gout and purine disorders

A 55-year-old businessman from Surat wakes at night with a hot, red, very painful swollen right great toe the day after a wedding feast with alcohol. The joint is aspirated in casualty and examined under polarised light. Which finding confirms the likely diagnosis?

A 20-year-old man in a Kolkata OPD has had two attacks of gout and passed a uric acid stone. He has normal intelligence and no abnormal movements. His uncle had similar problems. HGPRT activity in his red cells is about 10% of normal. Why does he overproduce uric acid?

A 34-year-old woman with rheumatoid arthritis has been well controlled on leflunomide for two years at a rheumatology clinic in Pune. She now wants to become pregnant. Which step of nucleotide synthesis does her drug block?

A 56-year-old man of Han Chinese descent working in Kolkata has recurrent gout with tophi. Before starting urate-lowering therapy he tests positive for HLA-B*58:01, so his physician avoids allopurinol and prescribes febuxostat. How does febuxostat lower serum uric acid?

A 15-year-old boy with glycogen storage disease type I (doll-like face, large liver, fasting hypoglycaemia and lactic acidosis) is seen in a Vellore clinic with a painful swollen ankle. Serum uric acid is 10.5 mg/dL. Which mechanism contributes to his hyperuricaemia?

A 35-year-old woman who received a kidney transplant in Ahmedabad is maintained on tacrolimus, prednisolone and mycophenolate mofetil. Mycophenolate acts mainly on lymphocytes because they depend on de novo purine synthesis. Which enzyme does it inhibit?