PKU and alkaptonuria vs Maple syrup urine disease and homocystinuria
How to tell PKU and alkaptonuria and Maple syrup urine disease and homocystinuria apart when a board question makes them look alike.
PKU is musty phenylalanine toxicity; alkaptonuria is dark urine/ochronosis; MSUD is sweet branched-chain amino acids; homocystinuria is thrombosis and lens down/in.
Side by side
PKU causes musty odor, intellectual disability, seizures, eczema, and hypopigmentation from phenylalanine hydroxylase or BH4 problems; alkaptonuria causes dark urine and ochronosis.
Maple syrup urine disease causes sweet-smelling urine, poor feeding, neurologic injury, and branched-chain amino acid buildup; homocystinuria causes lens subluxation down/in, thrombosis, marfanoid habitus, and osteoporosis.
Phenylalanine catabolism or homogentisate metabolism is impaired, leading to toxic aromatic amino acid metabolites.
Branched-chain alpha-ketoacid dehydrogenase deficiency or cystathionine beta-synthase/MTHFR defects disrupt branched-chain or sulfur amino acid handling.
High phenylalanine with low tyrosine supports PKU; urine darkening on standing supports alkaptonuria.
Elevated leucine/isoleucine/valine supports maple syrup urine disease; high homocysteine or methionine supports homocystinuria.
The trap
Odor clues are helpful but not enough; pair them with amino acid, lens direction, thrombosis, and urine darkening.
The repair move
For amino acid disorders, identify the accumulated amino acid and one signature non-lab clue.
Try a free question
CoreA 6-month-old infant whose family did not have access to newborn screening presents with progressive intellectual disability, eczema, hypopigmented hair and skin, musty body odor, and seizures. Plasma shows markedly elevated phenylalanine with low tyrosine. Which enzyme is deficient?
Show answer and explanation
Answer: A. Phenylalanine hydroxylase (classic PKU). Classic phenylketonuria is phenylalanine hydroxylase deficiency; accumulated phenylalanine is shunted to phenylketones causing musty odor and is neurotoxic. Tyrosine becomes essential; melanin and catecholamine precursors decrease, producing hypopigmentation.
Why the other choices are tempting
- B. Homogentisate oxidase deficiency (alkaptonuria) causes dark urine on standing and ochronosis in adulthood, not infantile intellectual disability with musty odor.
- C. Branched-chain alpha-ketoacid dehydrogenase deficiency (MSUD) causes SWEET maple syrup urine odor, not musty odor.
- D. Cystathionine beta-synthase deficiency (homocystinuria) causes lens subluxation downward and thrombosis, not pure musty intellectual disability.
- E. Tyrosinase deficiency causes albinism without intellectual disability or elevated phenylalanine.
Flashcards
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What clue supports PKU and alkaptonuria?
Choose PKU and alkaptonuria when the stem gives this pattern: PKU causes musty odor, intellectual disability, seizures, eczema, and hypopigmentation from phenylalanine hydroxylase or BH4 problems; alkaptonuria causes dark urine and ochronosis.
What clue supports Maple syrup urine disease and homocystinuria?
Choose Maple syrup urine disease and homocystinuria when the stem gives this contrasting pattern: Maple syrup urine disease causes sweet-smelling urine, poor feeding, neurologic injury, and branched-chain amino acid buildup; homocystinuria causes lens subluxation down/in, thrombosis, marfanoid habitus, and osteoporosis.
Quick answers
What is the fastest way to tell PKU and alkaptonuria from Maple syrup urine disease and homocystinuria?
PKU is musty phenylalanine toxicity; alkaptonuria is dark urine/ochronosis; MSUD is sweet branched-chain amino acids; homocystinuria is thrombosis and lens down/in.
What is the key clue for PKU and alkaptonuria?
PKU causes musty odor, intellectual disability, seizures, eczema, and hypopigmentation from phenylalanine hydroxylase or BH4 problems; alkaptonuria causes dark urine and ochronosis.
What is the key clue for Maple syrup urine disease and homocystinuria?
Maple syrup urine disease causes sweet-smelling urine, poor feeding, neurologic injury, and branched-chain amino acid buildup; homocystinuria causes lens subluxation down/in, thrombosis, marfanoid habitus, and osteoporosis.
What is the common trap with PKU and alkaptonuria vs Maple syrup urine disease and homocystinuria?
Odor clues are helpful but not enough; pair them with amino acid, lens direction, thrombosis, and urine darkening.