Proteins, haemoglobin and porphyrias

16 NEET-PG practice questions on Proteins, haemoglobin and porphyrias, 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.

1. Question 1 · Hard

   A 30-year-old man in Pune is found at a blood donation camp to have Hb 19.2 g/dL and haematocrit 57%. He is well, has no splenomegaly, and SpO2 is 98% on room air. He does not smoke and carboxyhaemoglobin is 1%. JAK2 V617F and exon 12 tests are negative, serum erythropoietin is within the reference range, and renal ultrasound is normal. His father also has a 'high haemoglobin'. The P50 of his oxygen dissociation curve is 17 mmHg (reference 26-27 mmHg). What is the most likely diagnosis?

   1. AHigh oxygen-affinity haemoglobin variant
   2. BHypoxic secondary erythrocytosis
   3. CPolycythaemia vera
   4. DErythropoietin-secreting renal tumour

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   Answer: A · High oxygen-affinity haemoglobin variant

   A low P50 means his haemoglobin holds oxygen too tightly (curve shifted left), so the tissues, including the kidney, sense hypoxia despite normal arterial saturation and keep erythropoietin inappropriately normal, driving erythrocytosis. With a family history this points to an inherited high-affinity haemoglobin variant, usually a mutation at the alpha1-beta2 interface or the 2,3-BPG binding site; some variants are not seen on HPLC, so P50 measurement is the key test. 2,3-BPG deficiency can give the same picture and is checked next. Most patients need no treatment, and venesection is used cautiously, if at all.

   • B: Hypoxic erythrocytosis needs low arterial saturation; his is 98%.
   • C: Polycythaemia vera is JAK2-positive with low erythropoietin and a normal P50.
   • D: A renal tumour would show on ultrasound and would not lower the P50.

2. Question 2 · Medium

   A 28-year-old man collapses with sudden abdominal pain and shock; at laparotomy, a ruptured splenic artery is found. He has thin, translucent skin with visible veins, bruises easily, and had a spontaneous colon perforation two years ago. His mother died of an aortic rupture at 35. A defect in which gene is most likely?

   1. ACOL5A1 (type V collagen)
   2. BCOL3A1 (type III collagen)
   3. CFBN1 (fibrillin-1)
   4. DCOL1A1 (type I collagen)

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   Answer: B · COL3A1 (type III collagen)

   Arterial and bowel rupture, thin translucent skin, easy bruising and a dominant family history of early vascular death are vascular Ehlers-Danlos syndrome, caused by mutations in COL3A1. Type III collagen is abundant in the walls of arteries, bowel and uterus, so these hollow organs rupture. Joint hypermobility is usually limited to small joints. Patients need counselling about pregnancy risk and avoidance of invasive procedures where possible.

   • A: COL5A1 defects cause classical EDS, with hyperextensible skin and atrophic scars.
   • C: FBN1 defects cause Marfan syndrome, with aortic root dilatation and tall stature.
   • D: COL1A1 defects mainly cause osteogenesis imperfecta.

3. Question 3 · Easy

   A 26-year-old primigravida at 30 weeks, a biology teacher, asks in the antenatal clinic how her baby can take oxygen from her blood across the placenta. Which property of fetal haemoglobin explains this?

   1. ATight binding of 2,3-BPG by its gamma chains
   2. BWeak binding of 2,3-BPG by its gamma chains
   3. CIron held in the ferric rather than ferrous state
   4. DTwice as many haem groups per molecule

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   Answer: B · Weak binding of 2,3-BPG by its gamma chains

   Fetal haemoglobin (alpha2 gamma2) binds 2,3-bisphosphoglycerate poorly, because the gamma chains lack the positively charged residues that hold 2,3-BPG in the central cavity of adult haemoglobin. With less 2,3-BPG bound, HbF has a higher oxygen affinity, its dissociation curve lies to the left of maternal blood, and oxygen moves from maternal to fetal blood in the placenta. This high affinity is also why raising HbF helps in sickle cell disease and beta-thalassaemia.

   • A: Tight 2,3-BPG binding would lower oxygen affinity, the opposite of what the fetus needs.
   • C: Ferric iron cannot carry oxygen; that is methaemoglobin.
   • D: Each haemoglobin molecule, fetal or adult, has four haem groups.

4. Question 4 · Medium

   A 34-year-old man on dapsone for dermatitis herpetiformis comes with breathlessness and slate-grey cyanosis. SpO2 is 85% and does not improve with oxygen, but arterial PaO2 is 98 mmHg. His blood is chocolate brown and does not redden when exposed to air. Methaemoglobin is 32%, and G6PD activity is normal. What is the next best step?

   1. AHyperbaric oxygen therapy
   2. BIntravenous sodium bicarbonate
   3. CExchange blood transfusion
   4. DIntravenous methylene blue

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   Answer: D · Intravenous methylene blue

   Dapsone oxidises haem iron from ferrous to ferric, forming methaemoglobin, which cannot carry oxygen and shifts the curve of the remaining haemoglobin to the left. Cyanosis that does not respond to oxygen with a normal PaO2 and a 'saturation gap' is typical. Symptomatic methaemoglobinaemia, usually above about 20-30%, is treated with IV methylene blue, which NADPH-methaemoglobin reductase reduces to leucomethylene blue, which in turn reduces methaemoglobin back to haemoglobin. It needs NADPH from the pentose phosphate pathway, so it fails and can cause haemolysis in G6PD deficiency.

   • A: Hyperbaric oxygen is used in carbon monoxide poisoning, not first for methaemoglobinaemia.
   • B: Bicarbonate does not reduce ferric iron and does not treat the cause.
   • C: Exchange transfusion is kept for failure of methylene blue or G6PD deficiency.

5. Question 5 · Easy

   Glycine must occupy every third position of the collagen triple helix because:

   1. AIt is the residue hydroxylated by vitamin C enzymes
   2. BIt forms the covalent cross-links between chains
   3. CIt carries the sugars added in the Golgi
   4. DIts small side chain fits the crowded helix centre

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   Answer: D · Its small side chain fits the crowded helix centre

   The three alpha chains of collagen wind tightly around each other, and every third residue faces the centre of the triple helix, where there is room only for the hydrogen atom side chain of glycine. This gives the Gly-X-Y repeat, with X often proline and Y often hydroxyproline. Replacing one glycine with a bulkier amino acid distorts the helix, which is the commonest mutation in osteogenesis imperfecta. Hydroxylation and cross-linking involve proline and lysine, not glycine.

   • A: Prolyl and lysyl hydroxylases act on proline and lysine, not glycine.
   • B: Cross-links form from lysine and hydroxylysine aldehydes made by lysyl oxidase.
   • C: Sugars are attached to hydroxylysine residues.

6. Question 6 · Medium

   A 16-year-old girl with hereditary spherocytosis has become more jaundiced and pale during a viral fever. Her spleen is palpable. Which urine findings are expected?

   1. ABilirubin absent, urobilinogen increased
   2. BBilirubin present, urobilinogen increased
   3. CBilirubin absent, urobilinogen absent
   4. DBilirubin present, urobilinogen absent

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7. Question 7 · Hard

   A 3-week-old term girl, born to consanguineous parents in Kozhikode, has persistent jaundice. Total bilirubin is 18 mg/dL with direct bilirubin 0.6 mg/dL. Hb, reticulocyte count, direct Coombs test, G6PD and thyroid function are normal, and she is feeding well. After two weeks of oral phenobarbital, her total bilirubin falls to 8 mg/dL. What is the most likely diagnosis?

   1. AGilbert syndrome
   2. BBreast milk jaundice
   3. CCrigler-Najjar syndrome type 2
   4. DCrigler-Najjar syndrome type 1

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8. Question 8 · Medium

   A 52-year-old man with chronic hepatitis C who drinks heavily has fragile skin on the backs of his hands, with blisters and erosions after minor trauma that heal with scars and milia. He also has excess facial hair. His urine fluoresces pink-red under a Wood's lamp. Deficiency of which enzyme is most likely?

   1. AFerrochelatase
   2. BHydroxymethylbilane synthase
   3. CUroporphyrinogen III synthase
   4. DUroporphyrinogen decarboxylase

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9. Question 9 · Medium

   A 4-year-old girl is brought to casualty in Bhopal with her third fracture in a year after minor falls. She has blue sclerae and lax joints, and the casualty officer considers child abuse before the paediatric review. Gene testing shows a glycine substitution in COL1A1. How does this mutation cause her disease?

   1. ALysyl oxidase cannot form cross-links
   2. BProline residues cannot be hydroxylated
   3. CFaulty chains disrupt helices of normal chains
   4. DProcollagen end peptides are not cleaved

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10. Question 10 · Medium

    A 24-year-old woman from Kollam is admitted with severe colicky abdominal pain, vomiting and constipation three weeks after starting oral contraceptive pills. Pulse 118/min, BP 150/96 mmHg; the abdomen is soft with no guarding. Serum sodium is 124 mmol/L. Her urine darkens to reddish-brown on standing in light, and a screening test for urinary porphobilinogen is positive. Her skin is normal. Deficiency of which enzyme is most likely?

    1. AALA dehydratase
    2. BUroporphyrinogen decarboxylase
    3. CFerrochelatase
    4. DHydroxymethylbilane synthase

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11. Question 11 · Medium

    A 9-year-old boy cries with burning pain in his face and hands within minutes of being out in the sun during school sports. The skin becomes red and swollen but never blisters. Urinary porphyrins are normal, and free protoporphyrin in his red cells is markedly raised. Deficiency of which enzyme is most likely?

    1. AHydroxymethylbilane synthase
    2. BUroporphyrinogen decarboxylase
    3. CCoproporphyrinogen oxidase
    4. DFerrochelatase

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12. Question 12 · Medium

    A 25-year-old woman has mild jaundice that worsened when she started oral contraceptive pills. Total bilirubin is 4.0 mg/dL, direct 2.9 mg/dL; ALT, ALP and GGT are normal. A laparoscopy done for another reason showed a dark, almost black liver. Consider four statements: 1. The defect is in the canalicular transporter MRP2. 2. The disease progresses to cirrhosis and needs transplant. 3. Total urinary coproporphyrin is normal, with over 80% as isomer I. 4. Phenobarbital lowers the bilirubin by inducing glucuronidation. Which statements are correct?

    1. A1 and 4 only
    2. B2 and 3 only
    3. C1, 3 and 4 only
    4. D1 and 3 only

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13. Question 13 · Hard

    A 34-year-old man with known acute intermittent porphyria is admitted after a weekend of heavy drinking and fasting, with severe abdominal pain, vomiting, serum sodium 128 mmol/L and one generalised seizure. The resident proposes: 1. IV haem arginate (haemin). 2. IV dextrose infusion as a carbohydrate load. 3. Morphine for the abdominal pain. 4. Phenobarbitone to prevent further seizures. Which parts of the plan are appropriate?

    1. A1, 2 and 3 only
    2. B1 and 3 only
    3. C1, 2 and 4 only
    4. D1 and 2 only

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14. Question 14 · Easy

    A 22-year-old MBBS student notices yellow eyes during exam week, when he skipped meals and had a viral fever. Total bilirubin is 3.2 mg/dL with direct bilirubin 0.3 mg/dL. Hb, reticulocyte count, peripheral smear, ALT and ALP are normal. The yellowness had occurred once before during a fast. What is the most likely diagnosis?

    1. ADubin-Johnson syndrome
    2. BHereditary spherocytosis
    3. CCrigler-Najjar syndrome type 1
    4. DGilbert syndrome

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15. Question 15 · Medium

    A 4-month-old boy is admitted with seizures, hypotonia and poor weight gain. His scalp hair is sparse, steel-coloured and twisted, and his mother's brother died in infancy. Serum copper and ceruloplasmin are low. Reduced activity of which enzyme weakens his blood vessels and connective tissue?

    1. ALysyl hydroxylase
    2. BProlyl hydroxylase
    3. CLysyl oxidase
    4. DProcollagen peptidase

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16. Question 16 · Medium

    A 38-year-old woman with type 2 diabetes and hereditary spherocytosis brings a glucometer diary with most fasting readings of 180-220 mg/dL. Her HbA1c is 5.6%. Her reticulocyte count is 9% and she has mild jaundice. Why does her HbA1c underestimate her glycaemia?

    1. AHer beta chains lack the terminal valine
    2. BHer red cells survive for a shorter time
    3. CBilirubin interferes with the HbA1c assay
    4. DSpherocytes take up less glucose than normal cells

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