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PORPHYRIA1

General
  Acute
  Biochemistry
  Genetics
Unsafe drugs

Acute Intermittent Porphyria
Coproporphyria
Variegate Porphyria
δ-aminolevulinic acid dehydratase deficiency

Also see: Tyrosinemia

Biochemistry: General


Genetics: General


Acute porphyrias: General


Acute Intermittent Porphyria

  Porphobilinogen deaminase (Hydroxymethylbilane synthase; HMBS) ; Chromosome 11q23.3; Dominant
  • Gene
    • More than 60 mutations
    • Mutation locations
      • Common sites: Exons 10, 12 & 14 (35% to 50%)
      • None in exons 2 & 13
      • Mutations commonly unique to individual or very few families
    • Mutation types: Missense 41%; Truncating 59%
    • Porphobilinogen deaminase deficient mice
      • Porphyric syndrome + Neuropathy
  • Clinical features: Acute attacks
    • More frequently manifest in females (65%) than males (35%)
    • Onset: Post puberty to 5th decade
    • Clinical features
      • Abdominal pain: Usually 1st sign of attacks; Precedes neuropathy
      • Neuropathy
        • Symmetric or Asymmetric
        • Motor
          • May be severe, cause respiratory failure
          • Proximal > Distal
        • Sensory
          • Loss: Usually mild, distal, symmetric
          • Pain syndrome: Diffuse, Proximal & Distal; Abdominal
        • Tendon reflexes: Reduced
        • Autonomic: Sympathetic & Parasympathetic involvement
          • Circulatory: Tachycardia, Blood pressure
          • Urinary retention
          • GI: Constipation; Nausea & Vomiting; Diarrhea
        • Cranial nerve: Facial; Dysphagia
      • CNS
        • Mental status changes: Psychosis; depression; Dementia
        • Seizures
    • Course
      • Duration: Days to Weeks
      • Usually complete recovery
      • Recurrence not uncommon
    • Laboratory
      • CSF: Often normal; Occasional mild increase in protein or cells
      • Nerve conduction studies
        • CMAPs: Small
        • No evidence of demyelination
        • Sensory: Normal or small SNAPs
      • EMG: Denervation; Some myopathic potentials
      • Pathology
        • Neuropathy: Predominantly axonal
        • CNS: Patchy demyelination
  • Other clinical features: No photosensitivity
  • Laboratory features: General
    • Reduced porphobilinogen deaminase in erythrocytes
      • EXCEPTION: Some mutations affect only non-erythroid tissues
    • Normal fecal coproporphyrin & protoporphyrin between attacks
    • Tests
      • Aminolevulinic acid: 24 hour urine
      • Aminolevulinic acid dehydratase : Erythrocyte
      • Porphobilinogen deaminase : Erythrocyte
      • Urinary porphobilinogen: High in 88% between attacks
  • Treatment
    • Hematin: Suppresses symptoms of acute attack by 3 or 4 days
    • Chlorpromazine: Abdominal pain & Psychotic disorders
    • Meperidine: Pain
    • Phenytoin: Probably least toxic anticonvulsant
    • Unsafe drugs: Numerous
  • History: King George III of England probably had porphyria

From: F Ford

Distal Atrophy
& Weakness:
Child



From: Virginia
King George III:
Later years

Coproporphyria

  Coproporphyrinogen 3 oxidase (CPOX) ; Chromosome 3q11.2; Dominant

Variegate Porphyria

  Protoporphyrinogen oxidase (PPOX) ; Chromosome 1q23.3; Dominant

Porphyria, Acute hepatic

  δ-aminolevulinate dehydratase (ALAD; PBGS) Chromosome 9q32; Recessive
PORPHYRIAS: UNSAFE DRUGS
Strong evidence Probably or Possibly unsafe
Androgens
Barbiturates
Estrogens
Ethanol
Griseofulvin
Hydantoins
Progesterones
Sulfonamides
Alkylkating agents
Aminophylline
Bemegride
Benzodiazepines
Bromobenzine
Carbamazepine
Chloramphenicol
Chlorpropamide
Clonidine
Chloroquine
Danazol
Dapsone
Disopyramide
Enflurane
Ergotamine
Etomidate
Eucalyptol
Glutethimide
Halothane
Hydralazine
Imipramine
Ketamine
Ketoconazole
Mepivacaine
Meprobamate
Methsuximide
Methyldopa
Metronidazole
Metyrapone
Miconazole
Nalidixic acid
Nifedipine
Nikethamide
Nitrazepam
Nortriptyline
Pentazocine
Phenazone
Phenoxybenzamine
Phensuxamide
Phenylbutazone
Primidone
Pyrazinamide
Rifampin
Spironolactone
Succinimides
Theophylline
Tolazemide
Tolbutamide
Trimethadone
Troxidone
Valproate
Verapamil


External links: Porphyria-Europe; Porphyria
Return to Motor Neuropathies
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References

1. Lancet 2005;365:241252

3/22/2012