Metal, Bilirubin, Porphyria & Vitamin Disorders

Copper (Wilson, Menkes) · Iron (hemochromatosis) · Zinc (acrodermatitis enteropathica) · Molybdenum cofactor deficiency · Bilirubin (Crigler-Najjar, Gilbert, Dubin-Johnson) · Porphyrias (acute intermittent, porphyria cutanea tarda) · Hereditary vitamin metabolism defects · Miscellaneous IEM
🧬 Key concepts: Wilson (Kayser-Fleischer rings, low ceruloplasmin), Menkes (kinky hair, copper deficiency), Crigler-Najjar (unconjugated hyperbilirubinemia), porphyria (neurovisceral attacks), vitamin-responsive disorders (biotin, B12, thiamine).

📖 Metal metabolism, bilirubin, porphyria & vitamin disorders

🔩 Metal disorders
Wilson (ATP7B): hepatic, neurological, Kayser-Fleischer rings, low ceruloplasmin. Menkes (ATP7A): kinky hair, copper deficiency, seizures. Hemochromatosis (HFE): iron overload. Acrodermatitis enteropathica (SLC39A4): zinc deficiency. Molybdenum cofactor deficiency: intractable seizures, dislocated lenses.
🟡 Bilirubin disorders
Unconjugated: Gilbert (UGT1A1 promoter), Crigler-Najjar type I/II (absent/reduced bilirubin conjugation). Conjugated: Dubin-Johnson (ABCC2), Rotor (SLCO1B1/3).
🧫 Porphyrias
Acute intermittent porphyria (PBGD deficiency): neurovisceral attacks, red urine. Porphyria cutanea tarda (UROD): photosensitivity, blistering. Erythropoietic protoporphyria (FECH): painful photosensitivity.
💊 Vitamin metabolism defects
Biotinidase deficiency (biotin responsive). Transcobalamin deficiency (B12 responsive). Thiamine-responsive megaloblastic anemia (SLC19A2).
⚠️ Red flags: Kayser-Fleischer rings + liver disease → Wilson. Kinky hair + seizures → Menkes. Self-mutilation + hyperuricemia → Lesch-Nyhan (purine). Acute abdominal pain + psychiatric symptoms + dark urine → acute porphyria.

🩺 Diagnostic approach to metal, bilirubin, porphyria & vitamin disorders

1
Copper disorders – Wilson: low serum ceruloplasmin, elevated 24h urinary copper, Kayser-Fleischer rings (slit lamp). Menkes: low serum copper and ceruloplasmin (copper deficiency), genetic testing ATP7A.
2
Bilirubin workup – Total/direct bilirubin. Unconjugated: Gilbert (normal LFTs, benign), Crigler-Najjar (marked elevation). Conjugated: Dubin-Johnson (black liver, normal br), Rotor.
3
Porphyria diagnosis – Urine porphobilinogen (PBG) and ALA during acute attack. Plasma fluorescence, fecal porphyrins. Enzyme assays (PBGD, UROD).
4
Vitamin-responsive disorders – Biotinidase assay, transcobalamin levels, thiamine pyrophosphate effect.
📌 Clinical pearl: A child with unexplained liver disease and neurological symptoms (dystonia, dysarthria) must have slit-lamp exam for Kayser-Fleischer rings to exclude Wilson disease.

📋 Stepwise management of metal, bilirubin, porphyria & vitamin disorders

1
Wilson disease – Copper chelation: D-penicillamine, trientine. Zinc acetate (maintenance, blocks copper absorption). Liver transplantation for fulminant failure.
2
Menkes disease – Subcutaneous copper histidine (early may improve neurological outcome). Supportive care.
3
Acrodermatitis enteropathica – Oral zinc supplementation (lifelong).
4
Crigler-Najjar type I – Phototherapy (12h/day), phenobarbital (ineffective), liver transplantation definitive.
5
Acute porphyria – IV hemin (suppresses ALA/PBG), IV glucose (10-20%), avoid triggers (drugs, fasting, hormones).
6
Biotinidase deficiency – Oral biotin (10-20 mg/day). Lifelong treatment.
🚨 Acute porphyria triggers: Barbiturates, sulfonamides, estrogens, anticonvulsants (phenytoin, carbamazepine), alcohol, fasting.

🧠 Reflex prompts: metal, bilirubin, porphyria, vitamin disorders

🟤 14-year-old with hepatitis, dystonia, dysarthria, and Kayser-Fleischer rings. Diagnosis?
Wilson disease (ATP7B). Low ceruloplasmin, high urinary copper. D-penicillamine.
🧬 Infant with kinky hair, seizures, hypothermia, and progressive neurodegeneration. Low serum copper, low ceruloplasmin. Diagnosis?
Menkes disease (ATP7A). Copper histidine early.
🧴 6-week-old with severe unconjugated hyperbilirubinemia, normal LFTs, no hemolysis. Phototherapy ineffective. Liver biopsy shows no UGT1A1 activity. Diagnosis?
Crigler-Najjar type I. Needs liver transplantation.
🤒 Teenager with acute abdominal pain, tachycardia, hyponatremia, dark urine. Family history of similar episodes. Diagnosis?
Acute intermittent porphyria (PBGD deficiency). Urine porphobilinogen. IV hemin.
🌞 Child with blistering rash on sun-exposed areas, hypertrichosis, and elevated urine uroporphyrins. Diagnosis?
Porphyria cutanea tarda (UROD deficiency). Phlebotomy, low-dose hydroxychloroquine.
🧴 Newborn with seizure, dislocated lenses, dysmorphic facies. Sulfite oxidase deficiency suspected. Diagnostic test?
Urine sulfite (test strip) and elevated S-sulfocysteine. Molybdenum cofactor deficiency.
🧪 Acrodermatitis enteropathica: periorificial rash, alopecia, diarrhea. Treatment?
Oral zinc supplementation.
🩸 Which porphyria presents with neurovisceral attacks (abdominal pain, neuropathy, psychosis) but no rash?
Acute intermittent porphyria (AIP).
💊 Treatment for biotinidase deficiency?
Oral biotin (10-20 mg/day).
🧬 Which inherited disorder causes iron overload (hepatic cirrhosis, diabetes, cardiomyopathy)?
Hereditary hemochromatosis (HFE gene). Phlebotomy.