Clinical Chemistry - Aminoacidopathies

Phenylketonuria (PKU)

Deficiency: Phenylalanine hydroxylase (PAH)

Issue: Can’t metabolize phenylalanine

Clinical Consequence: Chronic levels = toxic → Brain problems

Unique Features: Mousy odor in urine, Phenylketones in urine

Diagnostic Tests: PKU card, chromatography, Guthrie test, Ferric chloride, Fluorometry

Alkaptonuria

Deficiency: Homogentisate oxidase

Issue: Elevated homogentisic acid (HGA)

Clinical Consequence: Pigment deposits in cartilage + connective tissue

Unique Features: Not immediate, Urine turns black when exposed to air

Maple Syrup Urine Disease (MSUD)

Deficiency: Alpha-ketoacid-decarboxylase

Issue: Increase in branched amino acids (valine, leucine, isoleucine)

Clinical Consequence: Impaired mental development, failure to thrive

Unique Features: Urine/breath/sweat smells like maple syrup

Isovaleric Acidemia

Deficiency: Isovaleryl-CoA dehydrogenase 

Issue: Isovaleric acid buildup

Clinical Consequence: Brain + CNS damage

Unique Features: Urine smells like sweaty feet

Homocystinuria

Deficiency: Cystathionine-Beta-Synthase 

Issue: Increased homocysteine and methionine

Clinical Consequence: Heart attack/stroke at a young age, osteoporosis, detached eye lens, impaired mental dev, multi-systems affected

Unique Features: Treat with low methionine diet and high B6, early heart attack

Cystinuria

Deficiency: Issue in transport

Issue: Cystine builds up when it should be reabsorbed

Clinical Consequence: Bladder stones / crystals

Unique Features: The only defect in transport

Tyrosinemia

Deficiency: 3 types that differ based on deficiency type

Issue: Increased levels of tyrosine

Clinical Consequence: Type 1 - cancer, CNS, kidney/liver failure | Type 2 - eye, skin lesions

Unique Features: Type 1 is more severe. Each type depends on the deficient enzyme