A 7-month-old girl was picked up on newborn screening with raised phenylalanine and started on a phenylalanine-restricted diet. Her phenylalanine levels have since stayed in the target range, yet she has developed truncal hypotonia, limb rigidity, drooling, temperature instability and seizures. Serum prolactin is raised, and CSF shows low homovanillic acid and 5-hydroxyindoleacetic acid. Which defect best explains her course?

Dihydropteridine reductase deficiency

Classic phenylalanine hydroxylase deficiency

Aromatic L-amino acid decarboxylase deficiency

Tyrosine hydroxylase deficiency

A 2-day-old term boy in a Bengaluru NICU is comatose with a urea cycle defect suspected. Plasma ammonia was 520 µmol/L on admission and is 900 µmol/L six hours later (reference below 50 µmol/L), despite stopping feeds, a high-glucose infusion with insulin, intravenous sodium benzoate and sodium phenylacetate, and intravenous arginine. He is haemodynamically stable. What is the next best step?

Start haemodialysis without delay

Start intermittent peritoneal dialysis

Give lactulose and rifaximin by nasogastric tube

Perform a double-volume exchange transfusion

A 6-year-old boy from Nagpur, diagnosed elsewhere with spastic diplegic cerebral palsy, has a normal birth history but has been losing milestones, with gradually worsening stiffness of both legs and toe walking. Plasma arginine is markedly raised and ammonia is only mildly raised. What is the most likely diagnosis?

Carbamoyl phosphate synthetase I deficiency

Ornithine transcarbamoylase deficiency

Amino acid metabolism and inborn errors

26 NEET-PG practice questions on Amino acid metabolism and inborn errors, part of Biochemistry. The first 25 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 14-year-old tall, thin boy with learning difficulty is referred from the eye OPD with downward dislocation of both lenses. He had a deep vein thrombosis last year. Plasma total homocysteine and methionine are both markedly raised. Which vitamin should be tried first as treatment?
1. ABiotin (vitamin B7)
2. BThiamine (vitamin B1)
3. CPyridoxine (vitamin B6)
4. DNiacin (vitamin B3)
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Answer: C · Pyridoxine (vitamin B6)
Raised homocysteine with raised methionine, lens dislocation, a marfanoid build, learning difficulty and thrombosis indicate classic homocystinuria from cystathionine beta-synthase deficiency. This enzyme needs pyridoxal phosphate, and about half of patients respond to high-dose pyridoxine, which lowers homocysteine. Non-responders are treated with a methionine-restricted diet and betaine, with folate and B12 support. Lens dislocation is usually downward here, whereas in Marfan syndrome it is usually upward.
- A: Biotin treats biotinidase and holocarboxylase synthetase deficiencies.
- B: Thiamine is tried in thiamine-responsive maple syrup urine disease.
- D: Niacin is given in Hartnup disease, not in homocystinuria.
Question 2 · Easy
A 7-year-old girl with cystathionine beta-synthase deficiency, not responsive to pyridoxine, is put on a methionine-restricted diet by the paediatric metabolic team. Which amino acid becomes essential for her and must be supplemented?
1. ASerine
2. BCysteine
3. CMethionine
4. DTyrosine
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Answer: B · Cysteine
Cysteine is normally made from homocysteine and serine through cystathionine, using cystathionine beta-synthase and then cystathionase. When CBS is deficient, cysteine cannot be formed, so it becomes a conditionally essential amino acid and is added to the diet. In the same way tyrosine becomes essential in PKU. Betaine and, where needed, folate and B12 are added to lower homocysteine further.
- A: Serine is a substrate for CBS and is made in the body from glycolytic intermediates.
- C: Methionine is the amino acid being restricted, because it is the source of homocysteine.
- D: Tyrosine becomes essential in phenylketonuria, not in homocystinuria.
Question 3 · Hard
A 7-month-old girl was picked up on newborn screening with raised phenylalanine and started on a phenylalanine-restricted diet. Her phenylalanine levels have since stayed in the target range, yet she has developed truncal hypotonia, limb rigidity, drooling, temperature instability and seizures. Serum prolactin is raised, and CSF shows low homovanillic acid and 5-hydroxyindoleacetic acid. Which defect best explains her course?
1. ADihydropteridine reductase deficiency
2. BClassic phenylalanine hydroxylase deficiency
3. CAromatic L-amino acid decarboxylase deficiency
4. DTyrosine hydroxylase deficiency
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Answer: A · Dihydropteridine reductase deficiency
Tetrahydrobiopterin (BH4) is the cofactor for phenylalanine, tyrosine and tryptophan hydroxylases, so a defect in BH4 synthesis or recycling (dihydropteridine reductase) causes hyperphenylalaninaemia plus deficiency of dopamine and serotonin. Diet controls the phenylalanine but cannot replace the neurotransmitters, so the child deteriorates; low CSF HVA and 5-HIAA and a high prolactin (loss of dopamine's inhibition) confirm this. Every infant with raised phenylalanine should therefore have pterin studies and DHPR activity checked. Treatment adds L-dopa with carbidopa and 5-hydroxytryptophan, and folinic acid in DHPR deficiency.
- B: Classic PKU responds fully to diet; neurological decline with good phenylalanine control points to a cofactor defect.
- C: AADC deficiency lowers dopamine and serotonin but does not cause hyperphenylalaninaemia.
- D: Tyrosine hydroxylase deficiency lowers dopamine but does not raise phenylalanine.
Question 4 · Hard
A 2-day-old term boy in a Bengaluru NICU is comatose with a urea cycle defect suspected. Plasma ammonia was 520 µmol/L on admission and is 900 µmol/L six hours later (reference below 50 µmol/L), despite stopping feeds, a high-glucose infusion with insulin, intravenous sodium benzoate and sodium phenylacetate, and intravenous arginine. He is haemodynamically stable. What is the next best step?
1. AStart intermittent peritoneal dialysis
2. BGive lactulose and rifaximin by nasogastric tube
3. CStart haemodialysis without delay
4. DPerform a double-volume exchange transfusion
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Answer: C · Start haemodialysis without delay
Neonatal hyperammonaemia this severe and rising despite full medical treatment causes irreversible brain damage within hours, so ammonia must be removed by extracorporeal means. Haemodialysis, or continuous renal replacement therapy where haemodialysis is not possible, clears ammonia far faster than other methods. Medical treatment continues alongside dialysis to stop catabolism and divert nitrogen. Coma duration and peak ammonia are the main predictors of neurological outcome, so the decision should not wait.
- A: Peritoneal dialysis clears ammonia much more slowly than haemodialysis or CRRT.
- B: Lactulose and rifaximin act on gut ammonia in hepatic encephalopathy and are far too slow here.
- D: Exchange transfusion removes very little ammonia and is no longer recommended.
Question 5 · Medium
A 6-year-old boy from Nagpur, diagnosed elsewhere with spastic diplegic cerebral palsy, has a normal birth history but has been losing milestones, with gradually worsening stiffness of both legs and toe walking. Plasma arginine is markedly raised and ammonia is only mildly raised. What is the most likely diagnosis?
1. AArginase 1 deficiency
2. BCarbamoyl phosphate synthetase I deficiency
3. CArgininosuccinic aciduria
4. DOrnithine transcarbamoylase deficiency
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Answer: A · Arginase 1 deficiency
Arginase 1 deficiency, the last step of the urea cycle, usually does not cause neonatal hyperammonaemic coma, because some nitrogen can still leave as other compounds. Instead it causes a progressive spastic diplegia with developmental regression, often misdiagnosed as cerebral palsy; the markedly raised plasma arginine is the clue. A child with 'cerebral palsy' and a normal birth history who is losing skills should have metabolic tests. Treatment is a protein-restricted diet and nitrogen scavengers, without the arginine supplements used in other urea cycle defects.
- B: CPS I deficiency causes severe neonatal hyperammonaemia with low citrulline and arginine.
- C: Argininosuccinic aciduria raises argininosuccinic acid, with brittle hair and liver disease.
- D: OTC deficiency causes hyperammonaemic crises with low arginine and citrulline.
Question 6 · Medium
A 22-year-old man has had recurrent renal colic since his teens; stones have been removed twice. Urine microscopy shows flat hexagonal crystals and the cyanide-nitroprusside test is positive. Besides cystine, which amino acids are lost in excess in his urine?
1. AGlycine, proline and hydroxyproline
2. BOrnithine, lysine and arginine
3. CLeucine, isoleucine and valine
4. DTryptophan, alanine and serine
Answer and explanation in LearnFree account
Question 7 · Hard
A 16-year-old boy with cystathionine beta-synthase deficiency that does not respond to pyridoxine is listed for removal of a dislocated lens. The anaesthetist and the metabolic team discuss four points: 1. He is at increased risk of perioperative thromboembolism, so hydration and early mobilisation matter. 2. Betaine lowers his homocysteine by donating a methyl group to remethylate it. 3. His lens dislocation results from a mutation in the fibrillin-1 gene. 4. Nitrous oxide should be avoided during anaesthesia. Which points are correct?
1. A2, 3 and 4 only
2. B1, 3 and 4 only
3. C1, 2 and 4 only
4. D2 and 4 only
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Question 8 · Medium
A 15-year-old girl from Kochi has had episodes of vomiting, headache and confusion after high-protein meals since childhood, and she avoids meat and eggs. During an episode her ammonia is 210 µmol/L (reference below 50 µmol/L) and urine orotic acid is raised. Her only brother died on his fourth day of life with a similar illness. What is the mode of inheritance of her disorder?
1. AAutosomal recessive
2. BMitochondrial
3. CAutosomal dominant
4. DX-linked
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Question 9 · Easy
A 48-year-old mason from Jodhpur has had low back pain and stiff knees for years. His ear cartilage looks slate-blue, there are dark patches on the sclera, and his wife says urine left standing in the toilet turns black. X-ray of the spine shows calcified intervertebral discs. Which compound accumulates in this disorder?
1. APhenylpyruvic acid
2. BHomogentisic acid
3. CMelanogen
4. DPorphobilinogen
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Question 10 · Medium
A private hospital in Chennai wants to expand its newborn screening. The neonatologist asks for one method that can test the heel-prick dried blood spot for phenylketonuria, maple syrup urine disease, homocystinuria, several urea cycle defects, organic acidaemias and fatty acid oxidation defects in a single run. Which method meets this need?
1. AThin-layer chromatography of urine
2. BFerric chloride test on urine
3. CTandem mass spectrometry
4. DGuthrie bacterial inhibition assay
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Question 11 · Medium
A 9-year-old boy from a village near Solapur has a red, scaly rash on his face, neck and forearms that worsens in the sun, and episodes of unsteady gait. His diet is adequate. Urine chromatography shows increased neutral amino acids, including tryptophan, while plasma amino acids are low-normal. What is the underlying defect?
1. ADefective neutral amino acid transporter
2. BDefective dibasic amino acid transporter
3. CLow dietary niacin from a maize-based diet
4. DTryptophan diverted by a carcinoid tumour
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Question 12 · Medium
A 3-day-old boy, born at term after a normal pregnancy, becomes lethargic, feeds poorly and starts breathing fast. Plasma ammonia is 420 µmol/L (reference below 50 µmol/L), ABG shows respiratory alkalosis, plasma citrulline is low and urine orotic acid is markedly raised. Why is orotic acid raised in this baby?
1. ACarbamoyl phosphate spills into pyrimidine synthesis
2. BHepatocyte necrosis releases stored orotic acid
3. CAmmonia directly inhibits UMP synthase in the liver
4. DLow arginine blocks the renal excretion of orotate
Answer and explanation in LearnFree account
Question 13 · Easy
A 10-month-old boy from a village in Haryana, born at home and never screened, is brought for delayed sitting and two seizures. He has lighter hair and skin than his siblings, an eczematous rash and a musty, mousy odour to his urine. Which enzyme is most likely deficient?
1. ATyrosinase
2. BHomogentisate oxidase
3. CPhenylalanine hydroxylase
4. DTyrosine aminotransferase
Answer and explanation in LearnFree account
Question 14 · Medium
A 9-day-old girl in a Coimbatore NICU has poor feeding, encephalopathy and a sweet odour of urine and cerumen. Plasma leucine, isoleucine and valine are all raised. Which plasma finding is the most specific confirmation of the suspected disorder?
1. APresence of alloisoleucine
2. BRaised succinylacetone
3. CRaised argininosuccinate
4. DRaised homocitrulline
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Question 15 · Easy
A 6-day-old boy, born to consanguineous parents in Malappuram, stops feeding, becomes lethargic and develops opisthotonus with alternating hypertonia. The nurse notices a sweet, burnt-sugar odour in his nappies. Deficiency of which enzyme is most likely?
1. AIsovaleryl-CoA dehydrogenase
2. BBranched-chain aminotransferase
3. CBranched-chain alpha-ketoacid dehydrogenase
4. DPropionyl-CoA carboxylase
Answer and explanation in LearnFree account
Question 16 · Hard
A 19-year-old engineering student is admitted to a neurology ward in Pune with headache and seizures from cerebral venous sinus thrombosis. He has mild learning difficulty but no lens dislocation and a normal build. Plasma total homocysteine is 140 µmol/L (reference 5-15 µmol/L) and plasma methionine is 8 µmol/L (reference 15-40 µmol/L). Serum vitamin B12 and folate are normal. Which defect is most likely?
1. ASevere methylenetetrahydrofolate reductase deficiency
2. BCystathionine beta-synthase deficiency
3. CCystathionine gamma-lyase deficiency
4. DDietary vitamin B12 deficiency
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Question 17 · Medium
A 2-month-old boy is admitted to a Lucknow hospital with vomiting, lethargy and fast breathing. ABG shows metabolic acidosis with a high anion gap; urine ketones are strongly positive, ammonia is moderately raised and there is neutropenia. Urine organic acids show a large excess of methylmalonic acid, and serum vitamin B12 is normal. Which vitamin should be tried first, to see whether he responds?
1. AHydroxocobalamin
2. BBiotin
3. CThiamine
4. DPyridoxine
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Question 18 · Medium
A 24-year-old woman with classic phenylketonuria, diagnosed at birth, stopped her diet at the age of 12 and has normal intelligence. She comes to the antenatal OPD of a medical college planning her first pregnancy. Her plasma phenylalanine is well above the treatment target. What is the most appropriate advice?
1. ANo change, as the fetus can only be a carrier
2. BStart the diet once the first trimester is over
3. CTake high-dose folic acid alone through pregnancy
4. DRestart a strict low-phenylalanine diet before conception
Answer and explanation in LearnFree account
Question 19 · Medium
A 3-year-old boy from Indore has developmental delay, an enlarged liver and episodes of vomiting and drowsiness after illnesses. His hair is dry and breaks easily, and a hair-shaft mount shows nodes with frayed ends (trichorrhexis nodosa). During an episode ammonia is moderately raised. Which metabolite would be raised in his plasma and urine?
1. AArgininosuccinic acid
2. BPhenylpyruvic acid
3. CHomogentisic acid
4. DMethylmalonic acid
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Question 20 · Hard
A 2-day-old girl in a Delhi NICU becomes comatose with tachypnoea. Plasma ammonia is 680 µmol/L (reference below 50 µmol/L), blood glucose and anion gap are normal, and ABG shows respiratory alkalosis. Plasma amino acids show raised glutamine and alanine with undetectable citrulline, and urine orotic acid is normal. Which enzyme is most likely deficient?
1. ACarbamoyl phosphate synthetase I
2. BArginase 1
3. COrnithine transcarbamoylase
4. DArgininosuccinate synthetase
Answer and explanation in LearnFree account
Question 21 · Medium
A 4-day-old girl, the second child of a consanguineous couple from Bareilly, becomes drowsy and starts vomiting. Plasma ammonia is 600 µmol/L (reference below 50 µmol/L). Plasma citrulline is about fifty times the upper reference limit, argininosuccinic acid is not detected and orotic acid is mildly raised. What is the most likely diagnosis?
1. AOrnithine transcarbamoylase deficiency
2. BHyperornithinaemia-hyperammonaemia-homocitrullinuria
3. CCitrullinaemia type 1
4. DArgininosuccinic aciduria
Answer and explanation in LearnFree account
Question 22 · Medium
An intern presents a case of classic phenylketonuria to his unit. The consultant asks him to judge four statements: 1. Tyrosine becomes an essential amino acid for the patient. 2. The musty odour is due to phenylacetate. 3. Hypopigmentation occurs partly because phenylalanine inhibits tyrosinase. 4. The disorder is inherited in an X-linked recessive pattern. Which statements are correct?
1. A1, 2 and 4 only
2. B2 and 3 only
3. C1, 2 and 3 only
4. D1 and 2 only
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Question 23 · Easy
A 5-year-old girl from Koraput, Odisha, is brought to the eye OPD with photophobia and nystagmus. She has white hair, very pale skin and pinkish-grey irides, and her parents are first cousins. Which enzyme is most likely defective?
1. APhenylalanine hydroxylase
2. BTyrosine hydroxylase
3. CTyrosinase
4. DHomogentisate oxidase
Answer and explanation in LearnFree account
Question 24 · Medium
A 5-year-old boy with ornithine transcarbamoylase deficiency is discharged from a Chandigarh hospital on a low-protein diet and oral sodium phenylbutyrate. How does this drug help remove waste nitrogen?
1. AIt increases the renal excretion of ammonia
2. BIt activates carbamoyl phosphate synthetase I
3. CIts metabolite conjugates with glutamine
4. DIts metabolite conjugates with glycine
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Question 25 · Medium
A 4-month-old boy from Hyderabad is admitted with failure to thrive, vomiting and a large liver. PT is markedly prolonged although bilirubin is only mildly raised, and X-rays show rickets. Urine has glucose, phosphate and generalised aminoaciduria, and the baby has a smell of boiled cabbage. Urine succinylacetone is markedly raised. What is the most likely diagnosis?
1. ATyrosinaemia type II
2. BHereditary tyrosinaemia type I
3. CHereditary fructose intolerance
4. DClassic galactosaemia
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Amino acid metabolism and inborn errors

A 14-year-old tall, thin boy with learning difficulty is referred from the eye OPD with downward dislocation of both lenses. He had a deep vein thrombosis last year. Plasma total homocysteine and methionine are both markedly raised. Which vitamin should be tried first as treatment?

A 7-year-old girl with cystathionine beta-synthase deficiency, not responsive to pyridoxine, is put on a methionine-restricted diet by the paediatric metabolic team. Which amino acid becomes essential for her and must be supplemented?

A 22-year-old man has had recurrent renal colic since his teens; stones have been removed twice. Urine microscopy shows flat hexagonal crystals and the cyanide-nitroprusside test is positive. Besides cystine, which amino acids are lost in excess in his urine?

A 10-month-old boy from a village in Haryana, born at home and never screened, is brought for delayed sitting and two seizures. He has lighter hair and skin than his siblings, an eczematous rash and a musty, mousy odour to his urine. Which enzyme is most likely deficient?

A 9-day-old girl in a Coimbatore NICU has poor feeding, encephalopathy and a sweet odour of urine and cerumen. Plasma leucine, isoleucine and valine are all raised. Which plasma finding is the most specific confirmation of the suspected disorder?

A 6-day-old boy, born to consanguineous parents in Malappuram, stops feeding, becomes lethargic and develops opisthotonus with alternating hypertonia. The nurse notices a sweet, burnt-sugar odour in his nappies. Deficiency of which enzyme is most likely?

A 5-year-old girl from Koraput, Odisha, is brought to the eye OPD with photophobia and nystagmus. She has white hair, very pale skin and pinkish-grey irides, and her parents are first cousins. Which enzyme is most likely defective?

A 5-year-old boy with ornithine transcarbamoylase deficiency is discharged from a Chandigarh hospital on a low-protein diet and oral sodium phenylbutyrate. How does this drug help remove waste nitrogen?