Learn / FMK
Every FMK condition
299 diseases, deficiencies, toxicities and drug mechanisms harvested from every FMK deck — the ones sprinkled through a single bullet as much as the ones with their own slide. Pick what you're given and what you have to name, or let it cycle; distractors come from the same category so you have to discriminate (hypoketotic vs. ketotic hypoglycemia, which GSD, which urea-cycle enzyme…). Every answer shows the whole card with the lecture and slide.
Heme · FMK 08.4
Acute intermittent porphyria (AIP) Autosomal dominant
Defect / target: PBG deaminase (hydroxymethylbilane synthase, HMBS) - step 3
Mechanism: Heterozygotes retain ~50% HMBS activity; when CYP450 inducers, hormones or fasting deplete hepatic free heme and derepress ALAS1, the surge of ALA/PBG overwhelms the half-capacity enzyme and neurotoxic linear precursors (before ring closure) accumulate.
↑ Accumulates: Porphobilinogen (PBG) and delta-aminolevulinic acid (ALA)· ↓ Deficient: Hydroxymethylbilane / downstream heme (thin margin)
Presentation: Severe colicky abdominal pain without peritoneal signs, nausea/vomiting, anxiety, confusion, hallucinations, seizures, peripheral motor neuropathy, tachycardia, hypertension; women after puberty; NO photosensitivity; urine colorless when voided then darkens to reddish-brown/port-wine on standing in light and air (PBG oxidizes/polymerizes nonenzymatically)
Labs: Markedly elevated urine PBG (most specific) and ALA during an attack
Treatment: IV hemin (repletes heme pool, re-represses ALAS1), IV glucose/carbohydrate loading for mild attacks, stop porphyrinogenic drugs, supportive care; givosiran (siRNA against ALAS1) for recurrent attacks
The 'great masquerader'; precipitants = drugs, alcohol, hormones, fasting, infection/stress; 'give glucose and hemin, avoid inducers'; before ring closure = neurovisceral
Learn the mechanism: Heme synthesis (porphyrias) →
FMK 08.4 Heme Metabolism · slide 2, 10, 12, 16, 18, 30; handout