Master Biochemistry
for FMGE

What the FMGE Tests in Biochemistry

The FMGE Biochemistry exam tests the application of metabolic pathways to clinical presentations, including inborn errors of metabolism, vitamin deficiencies, and organ-specific enzyme derangements. Candidates must interpret laboratory values (e.g., LFTs, RFTs, cardiac enzymes), recognise diagnostic patterns (e.g., hyperammonaemia, metabolic acidosis), and select appropriate first-line treatments (e.g., N-acetylcysteine for paracetamol overdose, biotin for biotinidase deficiency). Emphasis is on inherited metabolic disorders (e.g., G6PD deficiency, phenylketonuria), porphyrias, glycogen storage diseases, and lysosomal storage disorders. Drug metabolism (e.g., CYP450, isoniazid acetylation) and nutritional biochemistry (e.g., thiamine in Wernicke’s encephalopathy, niacin in pellagra) are frequently tested. Questions often present a clinical scenario with abnormal biochemistry and require diagnosis, enzyme defect, or management step.

High-Yield Concepts

• Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency: X-linked recessive, most common in males of African, Mediterranean, or Asian descent. Triggers: oxidant drugs (primaquine, sulfonamides, nitrofurantoin), fava beans, infections. Presents with acute haemolytic anaemia, Heinz bodies on smear. Diagnosis: G6PD enzyme assay (normal 8-18 IU/gHb; deficiency <10% of normal). Avoid oxidant drugs; treat with supportive care and blood transfusion if severe.
• Phenylketonuria (PKU): Autosomal recessive deficiency of phenylalanine hydroxylase (PAH). Newborn screening: phenylalanine >120 µmol/L (2 mg/dL) is abnormal. Classic PKU: phenylalanine >1200 µmol/L. Treatment: low-phenylalanine diet (e.g., Phe-free formula) initiated by 3 weeks of age to prevent intellectual disability. Avoid aspartame (contains phenylalanine). Monitor blood phenylalanine target: 120-360 µmol/L in children.
• Maple Syrup Urine Disease (MSUD): Branched-chain alpha-keto acid dehydrogenase deficiency. Presents in neonates with poor feeding, lethargy, maple syrup odour in urine, and metabolic acidosis with elevated branched-chain amino acids (leucine, isoleucine, valine). Diagnosis: plasma amino acid analysis (leucine >200 µmol/L). Treatment: emergency removal of leucine via dialysis, then lifelong low-BCAA diet and thiamine supplementation (some respond).
• Porphyrias: Acute Intermittent Porphyria (AIP): Autosomal dominant deficiency of porphobilinogen deaminase (PBGD). Triggers: barbiturates, sulfonamides, alcohol, fasting. Presents with acute abdominal pain, neuropsychiatric symptoms, tachycardia, hypertension. Urine porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) elevated. First-line treatment: haem arginate (3 mg/kg IV daily) and glucose loading (300-500 g/day IV). Avoid precipitating drugs.
• Glycogen Storage Disease Type I (von Gierke Disease): Autosomal recessive deficiency of glucose-6-phosphatase. Presents in infancy with fasting hypoglycaemia, lactic acidosis, hypertriglyceridaemia, hyperuricaemia, hepatomegaly. Diagnosis: liver biopsy enzyme assay (glucose-6-phosphatase activity <10%). Treatment: uncooked cornstarch (1-2 g/kg every 4-6 hours) to maintain euglycaemia. Avoid fructose and galactose.
• Lysosomal Storage Disorders: Gaucher Disease Type I: Deficiency of glucocerebrosidase (beta-glucosidase). Presents with hepatosplenomegaly, bone pain (Erlenmeyer flask deformity on X-ray), thrombocytopenia, anaemia. Diagnosis: enzyme assay in leukocytes (glucocerebrosidase activity <15%). First-line treatment: enzyme replacement therapy (imiglucerase 60 U/kg IV every 2 weeks). Avoid splenectomy if possible.
• Vitamin B12 (Cobalamin) Deficiency: Causes: pernicious anaemia (autoimmune, intrinsic factor deficiency), gastrectomy, vegan diet, malabsorption (e.g., Crohn's, ileal resection). Presents with megaloblastic anaemia (MCV >100 fL), peripheral neuropathy, subacute combined degeneration of the spinal cord. Lab: low serum B12 (<148 pmol/L), elevated methylmalonic acid (MMA) and homocysteine. Treatment: hydroxocobalamin 1 mg IM every other day for 2 weeks, then 1 mg IM monthly for life.
• Acute Liver Failure: Paracetamol Overdose: Toxic dose: >150 mg/kg in adults. Presents with nausea, vomiting, then hepatic necrosis (ALT/AST >1000 IU/L, INR >1.5). Use Rumack-Matthew nomogram: treat if serum paracetamol level above treatment line (at 4 hours: >150 µg/mL). Antidote: N-acetylcysteine (NAC) IV loading dose 150 mg/kg in 200 mL D5W over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours. NAC most effective within 8 hours.

Common Traps in Biochemistry Questions

• Confusing acute intermittent porphyria with variegate porphyria: AIP has normal stool porphyrins, VP has elevated faecal protoporphyrin and coproporphyrin.
• Assuming all megaloblastic anaemias are B12 deficiency: folate deficiency also causes megaloblastosis but does not cause neurological symptoms and has normal MMA.
• Forgetting that G6PD deficiency is X-linked, so heterozygous females may have normal enzyme levels and not be at risk for haemolysis.
• Mixing up glycogen storage diseases: von Gierke (type I) causes fasting hypoglycaemia and lactic acidosis; McArdle (type V) causes exercise-induced myoglobinuria with normal fasting glucose.
• Thinking that PKU treatment can be stopped after childhood: lifelong dietary restriction is needed to prevent cognitive decline and executive dysfunction.
• Overlooking that paracetamol overdose can be missed if the patient presents late (>24 hours), when ALT may already be rising and NAC is still beneficial but less effective.

How to Revise Biochemistry for the FMGE

Prioritise memorising enzyme defects and key lab values for common inborn errors (PKU, MSUD, G6PD, von Gierke) and porphyrias. Focus on clinical presentations that link to specific biochemical pathways, e.g., hypoglycaemia with lactic acidosis suggests G6Pase deficiency. Practice interpreting nomograms (Rumack-Matthew) and diagnostic algorithms for hyperammonaemia (urea cycle defects vs organic acidaemias). Questions often present a case with a single abnormal lab value (e.g., elevated leucine) and ask for the defect or treatment. Spend time on vitamin deficiencies (B12, folate, thiamine, niacin) and their neurological/haematological features. Review drug metabolism pathways (CYP450, acetylation) and how they cause adverse effects (e.g., isoniazid-induced neuropathy in slow acetylators). Use flashcards for enzyme names and cofactors.

Practise it: MedLumen has 49 Biochemistry questions for the FMGE, each with a full explanation and references.