MRCP Part 1 Biochemistry: Inborn Errors of Metabolism

TL;DR: 

In MRCP Part 1, inborn errors of metabolism (IEMs) are tested through short clinical vignettes that link basic biochemistry to real-world presentations such as hypoglycaemia, metabolic acidosis, or hyperammonaemia. You do not need exhaustive enzyme lists—focus on patterns, hallmark labs, and age of presentation. This article explains the examinable scope, high-yield disorders, common traps, and how to revise them efficiently.

Why this topic matters in MRCP Part 1

Inborn errors of metabolism are a favourite for MRCP examiners because they integrate multiple disciplines—biochemistry, genetics, and clinical medicine—into a single, testable scenario. Rather than asking isolated factual questions, MRCP Part 1 uses IEMs to assess whether you can interpret laboratory data, recognise classic clinical patterns, and infer the underlying metabolic block.

For candidates, this is good news. Once you understand the logic behind a few core disorders, many questions become predictable. A neonate with vomiting and hyperammonaemia, a child with fasting hypoglycaemia and hepatomegaly, or a young adult with exercise intolerance all point towards specific metabolic pathways.

If you are following a structured MRCP Part 1 revision plan, IEMs should be revised after core carbohydrate and amino acid metabolism, but before full mock exams. A concise, pattern-based approach consistently yields marks.

Scope of inborn errors of metabolism tested in MRCP Part 1

MRCP Part 1 does not aim to test rare biochemical minutiae. Instead, the exam focuses on:

• Commonly taught IEMs with clear biochemical consequences

• Disorders presenting in neonates, infants, or early childhood

• Conditions associated with distinctive laboratory abnormalities

• Diseases that explain common exam scenarios (hypoglycaemia, acidosis, encephalopathy)

Advanced molecular genetics, detailed newborn screening algorithms, or experimental therapies are outside the expected scope.

Official guidance from the MRCP(UK) confirms that biochemistry questions emphasise applied understanding rather than rote recall of enzyme names👉 https://www.mrcpuk.org/mrcpuk-examinations/part-1

The five most tested IEM subtopics (high-yield focus)

1. Urea cycle disorders

Urea cycle defects lead to failure of ammonia detoxification.

Key exam points:

• Present with vomiting, lethargy, confusion, or coma

• Hyperammonaemia is the defining feature

• Early respiratory alkalosis due to hyperventilation

• Ornithine transcarbamylase (OTC) deficiency is X-linked

Examiner logic: ammonia is neurotoxic → raised ammonia + normal anion gap = think urea cycle.

2. Glycogen storage diseases (GSDs)

These disorders impair glycogen synthesis or breakdown.

Key exam points:

• Liver involvement → hepatomegaly, fasting hypoglycaemia

• Von Gierke disease (Type I): hypoglycaemia, lactic acidosis, hyperuricaemia

• Muscle forms → exercise intolerance, cramps, myoglobinuria

The exam usually tests the consequence (failure to maintain blood glucose), not the enzyme itself.

3. Galactosaemia

A classic neonatal metabolic emergency.

Key exam points:

• Vomiting, jaundice, hepatomegaly after milk feeds

• Risk of E. coli sepsis

• Cataracts due to galactitol accumulation

• Improves with dietary galactose restriction

This disorder is often used to test recognition of diet-related triggers.

4. Hereditary fructose intolerance

Frequently confused with galactosaemia but clinically distinct.

Key exam points:

• Symptoms after fruit, juice, or sucrose

• Hypoglycaemia and vomiting

• Strong aversion to sweet foods

• Liver dysfunction in severe cases

A careful dietary history usually gives the diagnosis away.

5. Phenylketonuria (PKU)

The prototype amino acid metabolism disorder.

Key exam points:

• Phenylalanine hydroxylase deficiency

• Intellectual disability if untreated

• Hypopigmentation and “musty” odour

• Management principle: dietary restriction, not drugs

PKU questions often test understanding of tyrosine as a conditionally essential amino acid.

High-yield summary table

Disorder group	Key biochemical clue	Typical presentation	Exam pearl
Urea cycle defects	↑ Ammonia, ↓ urea	Neonatal encephalopathy	Early respiratory alkalosis
Glycogen storage disease I	Hypoglycaemia, lactic acidosis	Hepatomegaly	Fasting intolerance
Galactosaemia	Liver dysfunction	Neonatal jaundice, cataracts	Milk-related symptoms
Fructose intolerance	Hypoglycaemia after fructose	Vomiting, aversion to sweets	Diet trigger is key
PKU	↑ Phenylalanine	Developmental delay	Dietary management

Exam-style mini-MCQ

A 4-day-old neonate presents with poor feeding and lethargy. Blood gas shows respiratory alkalosis. Serum ammonia is markedly elevated. Which diagnosis best explains these findings?

A. GalactosaemiaB. Glycogen storage diseaseC. Urea cycle disorderD. PhenylketonuriaE. Organic acidaemia

Correct answer: C. Urea cycle disorder

Explanation: Marked hyperammonaemia with respiratory alkalosis is characteristic of urea cycle defects. Organic acidaemias typically cause metabolic acidosis, while galactosaemia and PKU present with feeding-related or developmental features.

Regular practice with clinically framed questions like this—using a dedicated MRCP QBank—helps reinforce these distinctions👉 https://crackmedicine.com/qbank/

Common pitfalls in MRCP questions (and how to avoid them)

• Confusing acidosis with alkalosis Always read the blood gas carefully before deciding.

• Over-memorising enzyme names Focus on metabolic consequences instead.

• Ignoring age of onset Neonatal vs adolescent presentation is often decisive.

• Missing dietary triggers Milk, fructose, or fasting often provide the key clue.

• Assuming rarity equals irrelevance Some rare disorders are disproportionately tested because they illustrate core principles.

Practical study-tip checklist

Use this checklist when revising IEMs:

1. Group disorders by toxic accumulation vs energy deficiency

2. Memorise one hallmark lab abnormality per condition

3. Practise timed MCQs and review explanations carefully

4. Write a one-line “exam pearl” after each condition

5. Consolidate with full-length mock tests👉 https://crackmedicine.com/mock-tests/

This approach fits well within a broader MRCP Part 1 study plan👉 https://crackmedicine.com/mrcp-part-1/

FAQs

Are inborn errors of metabolism high-yield for MRCP Part 1?

Yes. They appear regularly because they test applied biochemistry using recognisable clinical patterns.

Do I need to memorise every enzyme defect?

No. Understanding the biochemical consequence and presentation is far more important.

How are IEM questions usually framed?

Most appear as short clinical vignettes with key laboratory clues.

What is the best resource to practise this topic?

A reliable MRCP QBank combined with mock tests provides the most exam-relevant practice.

Ready to start?

At Crack Medicine, our MRCP Part 1 QBank and mock tests are designed exactly for this—short vignettes, high-yield lab clues, and explanations that teach you why an answer is right (or wrong), not just what to memorise. Many candidates find that once they practise IEMs this way, these questions become some of the most predictable marks in the exam.

👉 Practise IEM questions here: https://crackmedicine.com/qbank/👉 Test your readiness with full mock exams: https://crackmedicine.com/mock-tests/👉 Explore a structured MRCP Part 1 revision plan: https://crackmedicine.com/mrcp-part-1/

Sources

• MRCP(UK) Examination Information: https://www.mrcpuk.org

• British Society for Inherited Metabolic Disease (BSIMD): https://www.bsimd.org.uk

• Orphanet – Metabolic Disorders Overview: https://www.orpha.net