Inborn Errors of Metabolism – IAP Quiz Q&A

Newborn Screening & Diagnostic Clues

Q1. What is the most useful bedside clue that often points to a specific inborn error of metabolism (IEM) in a sick neonate? A: An abnormal body or urine odor. Classic associations:

Maple syrup urine disease (MSUD) - sweet/maple syrup odor
Phenylketonuria (PKU) - mousy/musty odor (due to phenylacetic acid)
Isovaleric acidemia - sweaty feet odor
Hypermethioninemia/methionine adenosyltransferase deficiency - boiled cabbage/fishy odor
Trimethylaminuria (fish odor syndrome) - rotting fish odor (Brenner and Rector's The Kidney; Henry's Clinical Diagnosis and Management by Laboratory Methods)

Q2. Which single laboratory technology revolutionized expanded newborn screening, allowing simultaneous detection of dozens of amino acid and fatty acid oxidation disorders from one dried blood spot? A: Tandem mass spectrometry (acylcarnitine and amino acid profiling on a dried blood spot), first described for acylcarnitine profiling and now the backbone of expanded newborn screening panels. - Tietz Textbook of Laboratory Medicine

Q3. Name four IEMs commonly included in expanded newborn bloodspot screening panels. A: Phenylketonuria, congenital hypothyroidism (not strictly an IEM but co-screened), medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, maple syrup urine disease, isovaleric acidemia, glutaric aciduria type 1, homocystinuria. - Emery's Elements of Medical Genetics and Genomics

Q4. In a neonate, hyperammonemia detected in the first 24 hours of life versus after protein feeding begins suggests which two different categories of IEM respectively? A: Hyperammonemia within 24 hours - pyruvate carboxylase deficiency (and other organic acidemias); hyperammonemia after protein feeding starts - urea cycle enzyme defects. - Tintinalli's Emergency Medicine

Urea Cycle Disorders

Q5. What is the biochemical hallmark of all urea cycle disorders? A: Hyperammonemia with protein intolerance - the urea cycle fails to convert ammonia to urea, so ammonia accumulates and is toxic to the CNS. All are autosomal recessive except ornithine transcarbamylase (OTC) deficiency, which is X-linked. - Emery's Elements of Medical Genetics and Genomics; Biochemistry, Lippincott Illustrated Reviews

Q6. Which is the most common urea cycle disorder, and what is its inheritance pattern? A: Ornithine transcarbamylase (OTC) deficiency - the only X-linked urea cycle disorder (all others are autosomal recessive).

Q7. A drug used to treat acute hyperammonemia in N-acetylglutamate synthetase deficiency (and shown useful in other hyperammonemic states) is: A: Carglumic acid. - Thompson & Thompson Genetics and Genomics in Medicine

Q8. Why does arginine become an "essential" amino acid in patients with urea cycle defects? A: Because the urea cycle (which normally regenerates arginine) is disrupted, so dietary/supplemental arginine (or citrulline) is required, and it is used therapeutically along with protein restriction and ammonia scavengers (sodium benzoate, sodium phenylacetate). - Thompson & Thompson Genetics and Genomics in Medicine

Amino Acid Disorders

Q9. What enzyme is deficient in classic phenylketonuria (PKU), and what is its approximate incidence? A: Phenylalanine hydroxylase (PAH), which converts phenylalanine to tyrosine. Incidence is roughly 1 in 10,000-16,500 births (varies by population/textbook). - Goldman-Cecil Medicine; Harrison's Principles of Internal Medicine

Q10. What cofactor deficiency can mimic classic PKU biochemically, and what oral agent can help such patients? A: Tetrahydrobiopterin (BH4) deficiency (a cofactor for PAH) causes "malignant" or atypical PKU. Oral sapropterin (synthetic BH4) can lower phenylalanine levels in BH4-responsive patients. - Harrison's Principles of Internal Medicine

Q11. What enzyme defect causes maple syrup urine disease, and which amino acids accumulate? A: Branched-chain alpha-ketoacid dehydrogenase deficiency, causing accumulation of leucine, isoleucine, and valine (and their ketoacids). Presents in the first week of life with poor feeding, lethargy, decerebrate rigidity, seizures, and hypoglycemia if untreated. - Kaplan and Sadock's Synopsis of Psychiatry; Emery's Elements of Medical Genetics

Q12. Which vitamin has shown a therapeutic response in some forms of maple syrup urine disease? A: Thiamine (in thiamine-responsive MSUD variants). - Tietz Textbook of Laboratory Medicine

Q13. Which amino acid disorder is classically associated with downward lens dislocation, marfanoid habitus, and thromboembolic events, and what is the biochemical defect? A: Homocystinuria, most commonly due to cystathionine beta-synthase deficiency, leading to elevated homocysteine and methionine.

Carbohydrate Disorders

Q14. Classic galactosemia is caused by deficiency of which enzyme, and what are the key clinical features in a neonate? A: Galactose-1-phosphate uridylyltransferase (GALT) deficiency. Presents with vomiting, jaundice, sepsis (classically E. coli), cataracts, aminoaciduria, hepatomegaly, and failure to thrive after starting milk feeds. - Harrison's Principles of Internal Medicine; Robbins & Kumar Basic Pathology

Q15. Why are patients with classic galactosemia at increased risk of E. coli sepsis? A: Galactose and its metabolites impair neutrophil function/bactericidal activity, and accumulated galactitol contributes to organ toxicity; E. coli sepsis is a well-recognized presenting feature in the neonatal period.

Q16. Deficiency of galactokinase (galactosemia type II) causes which relatively isolated clinical feature, unlike classic (type I) galactosemia? A: Cataracts, generally without the severe hepatic, renal, or CNS involvement seen in classic (GALT-deficient) galactosemia. - Harrison's Principles of Internal Medicine

Q17. Von Gierke disease (glycogen storage disease type Ia) is due to deficiency of which enzyme, and what is its cardinal biochemical feature? A: Glucose-6-phosphatase deficiency - the most common glycogen storage disease causing severe fasting hypoglycemia, along with lactic acidosis, hyperuricemia, hyperlipidemia, and hepatomegaly. - Goldman-Cecil Medicine; Robbins, Cotran & Kumar Pathologic Basis of Disease

Q18. Name two other GSD subtypes besides type I that can also present with hypoglycemia. A: GSD type 0a, VI, IX, and XI, as well as fructose-1,6-bisphosphatase deficiency; in GSD type IV, hypoglycemia is a variable feature. - Goldman-Cecil Medicine

Lysosomal Storage Disorders

Q19. A "cherry-red spot" on fundus examination in an infant with progressive neurodegeneration and hepatosplenomegaly (absent in pure Tay-Sachs) suggests which two classic diagnoses? A: Tay-Sachs disease (GM2 gangliosidosis - hexosaminidase A deficiency; no hepatosplenomegaly) and Niemann-Pick disease type A (acid sphingomyelinase deficiency; with hepatosplenomegaly and failure to thrive). Other causes include Sandhoff disease, sialidosis, and galactosialidosis. - Kanski's Clinical Ophthalmology; Emery's Elements of Medical Genetics

Q20. Which lysosomal storage disease is X-linked (unlike most others, which are autosomal recessive), and what enzyme is deficient? A: Hunter syndrome (mucopolysaccharidosis type II) is X-linked recessive, due to deficiency of iduronate-2-sulfatase. (Hurler syndrome/MPS I, by contrast, is autosomal recessive, due to alpha-L-iduronidase deficiency.)

Q21. Gaucher disease is due to deficiency of which enzyme, and which ethnic group has the highest carrier frequency? A: Glucocerebrosidase (acid beta-glucosidase) deficiency, leading to accumulation of glucocerebroside in macrophages ("Gaucher cells"). Highest prevalence is in Ashkenazi Jewish populations.

Q22. Which lysosomal storage disorder can cause macroglossia and is a recognized cause of airway difficulty in anesthesia, along with Von Gierke disease? A: Hurler syndrome (mucopolysaccharidosis type I). - K J Lee's Essential Otolaryngology

Organic Acidemias & Fatty Acid Oxidation Defects

Q23. Which organic acidemias classically cause a high anion gap metabolic acidosis in a sick neonate? A: Methylmalonic acidemia, propionic acidemia, isovaleric acidemia, and maple syrup urine disease. - Morgan and Mikhail's Clinical Anesthesiology

Q24. Which fatty acid oxidation disorder classically presents with hypoketotic hypoglycemia, vomiting, and lethargy during a fasting illness, and can mimic Reye syndrome or present as sudden infant death? A: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency - one of the conditions included on expanded newborn screening panels via acylcarnitine profiling.

Quick-Fire Rapid Recall

Q25. Odor - maple syrup: Diagnosis? MSUD. Q26. Odor - mousy/musty: Diagnosis? PKU. Q27. Odor - sweaty feet: Diagnosis? Isovaleric acidemia. Q28. Odor - boiled cabbage: Diagnosis? Methionine adenosyltransferase deficiency / tyrosinemia. Q29. Odor - fishy: Diagnosis? Trimethylaminuria (fish odor syndrome) / hypermethioninemia. Q30. Enzyme deficient in classic galactosemia? GALT (galactose-1-phosphate uridylyltransferase). Q31. Enzyme deficient in PKU? Phenylalanine hydroxylase. Q32. Enzyme deficient in Von Gierke disease? Glucose-6-phosphatase. Q33. Screening test technology used in modern expanded NBS programs? Tandem mass spectrometry. Q34. Which urea cycle disorder is X-linked? OTC (ornithine transcarbamylase) deficiency.

Sources: Harrison's Principles of Internal Medicine 22E; Goldman-Cecil Medicine; Robbins & Kumar Basic Pathology; Robbins, Cotran & Kumar Pathologic Basis of Disease; Emery's Elements of Medical Genetics and Genomics; Thompson & Thompson Genetics and Genomics in Medicine; Henry's Clinical Diagnosis and Management by Laboratory Methods; Tietz Textbook of Laboratory Medicine, 7th Ed; Biochemistry (Lippincott Illustrated Reviews), 8th Ed; Kanski's Clinical Ophthalmology; Brenner and Rector's The Kidney; Tintinalli's Emergency Medicine.

A few facts (Hunter vs Hurler inheritance, Gaucher disease details, MCAD presentation) are supplemented from standard general medical knowledge rather than a direct textbook excerpt in this session — flagging that for your own verification before using them in a formal quiz.

If you want, I can convert this into a printable Word/PDF quiz sheet with a separate answer key, or expand any single topic (e.g., a deep dive purely on urea cycle disorders or lysosomal storage diseases) into more MCQ-style questions.

Give me like oneliner

Here's the same content converted into rapid one-liner Q&A format, ideal for a quiz round:

Inborn Errors of Metabolism – One-Liner Q&A

Enzyme deficient in classic PKU? → Phenylalanine hydroxylase
Odor in PKU? → Mousy/musty
Odor in MSUD? → Maple syrup/sweet
Enzyme deficient in MSUD? → Branched-chain alpha-ketoacid dehydrogenase
Vitamin responsive in some MSUD cases? → Thiamine
Odor in isovaleric acidemia? → Sweaty feet
Odor in hypermethioninemia? → Fishy/boiled cabbage
Odor in fish odor syndrome? → Rotting fish (trimethylaminuria)
Enzyme deficient in classic galactosemia? → GALT (galactose-1-phosphate uridylyltransferase)
Organism causing sepsis in galactosemia? → E. coli
Isolated cataracts without liver/CNS disease - which galactose disorder? → Galactokinase deficiency (galactosemia type II)
Most common glycogen storage disease causing hypoglycemia? → GSD type Ia (Von Gierke disease)
Enzyme deficient in Von Gierke disease? → Glucose-6-phosphatase
Biochemical hallmark of all urea cycle disorders? → Hyperammonemia
Only X-linked urea cycle disorder? → OTC (ornithine transcarbamylase) deficiency
Drug for acute hyperammonemia in NAGS deficiency? → Carglumic acid
Amino acid that becomes "essential" in urea cycle disorders? → Arginine
Cherry-red spot + no hepatosplenomegaly? → Tay-Sachs disease
Cherry-red spot + hepatosplenomegaly? → Niemann-Pick disease type A
Enzyme deficient in Tay-Sachs? → Hexosaminidase A
Enzyme deficient in Niemann-Pick type A? → Acid sphingomyelinase
X-linked mucopolysaccharidosis? → Hunter syndrome (MPS II)
Enzyme deficient in Hurler syndrome? → Alpha-L-iduronidase
Enzyme deficient in Gaucher disease? → Glucocerebrosidase
Ethnicity with highest Gaucher carrier rate? → Ashkenazi Jews
Cells seen in Gaucher disease? → Gaucher cells (lipid-laden macrophages)
Fatty acid oxidation defect mimicking Reye syndrome/SIDS? → MCAD deficiency
Technology used in expanded newborn screening? → Tandem mass spectrometry
Organic acidemias causing high anion gap acidosis? → Methylmalonic, propionic, isovaleric acidemia
Lens dislocation (downward) + marfanoid habitus + thrombosis? → Homocystinuria
Enzyme deficient in homocystinuria? → Cystathionine beta-synthase
Hyperammonemia within 24 hrs of life suggests? → Pyruvate carboxylase deficiency/organic acidemia
Hyperammonemia after starting protein feeds suggests? → Urea cycle defect
Cofactor deficiency mimicking PKU? → Tetrahydrobiopterin (BH4) deficiency
Oral drug for BH4-responsive PKU? → Sapropterin

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