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variegate porphyria (VP, mixed porphyria)

(See also porphyria) Etiology: 1) deficiency in protoporphyrinogen oxidase 2) inhibition of uroporphyrinogen I synthase by accumulated protoporphyrinogen 3) pharmaceutical which may precipitate acute attacks a) anesthetics: barbiturates, halothane b) anticonvulsants: - hydantoins, carbamazepine, ethosuximide, methsuximide, phensuximide, primidone c) antimicrobials - chloramphenicol, griseofulvin, novobiocin, pyrazinamide, sulfonamides d) ergot alkaloids e) ethanol f) hormones: estrogens, progestins g) imipramine h) methyldopa i) sedatives/hypnotics - chlordiazepoxide, diazepam, oxazepam, flurazepam, meprobamate j) pentazocine k) phenylbutazone l) sulfonylureas: chlorpropamide, tolbutamide m) theophylline * n) any drug that induces Cyt P450 will induce heme synthesis & potentially precipitate attack Epidemiology: 1) all races - especially prevalent in the white population of South Africa 2) onset after puberty 3) peak incidence: 2nd to 4th decades of life Pathology: 1) decreased protoporphyrinogen oxidase & subsequent protoporphyrinogen inhibition of uroporphyrinogen I synthase have been implicated 2) skin a) subepidermal bullae b) PAS-positive depositions in & around blood vessels in upper dermis Genetics: - associated with defects in protoporphyrinogen oxidase (PPOX) - associated with defects in HFE Clinical manifestations: 1) somewhat variable in presentation 2) skin lesions a) result from exposure to light, thus seasonal b) vesicles & bullae c) painful erosions from easily traumatized bullae d) atrophic scars at sites of erosions e) fragile skin f) milia g) periorbital heliotrope hue h) diffuse hyperpigmentation (melanoderma) on sun-exposed areas i) lesions localized to sun-exposed areas j) hypertrichosis 3) GI manifestations a) acute attacks of abdominal pain b) nausea/vomiting c) constipation 4) neuropsychiatric manifestations: a) peripheral neuropathy b) confusional state c) seizures d) depression e) coma f) cranial nerve involvement g) bulbar paralysis h) paresthesias 5) systemic manifestations: a) muscle weakness b) fever c) hypertension Laboratory: 1) fluorescent plasma with emission max at 626 nm 2) increased urine porphobilinogen during acute attack 3) elevated urine aminolevulinic acid (ALA) during acute attack 4) high protoporphyrin in feces 5) high coproporphyrin in feces 6) complete blood count (CBC): leukocytosis 7) serum iron, TIBC, serum ferritin - evidence of iron overload 8) HFE gene mutation Management: 1) prognosis - lifelong disease - good prognosis if precipitating factors are avoided 2) pharmaceutical agents - oral beta carotene may or may not control skin manifestations, but has no effect on systemic manifestations - narcotic analgesics for abdominal pain - phenothiazines (Compazine) for nausea - chloral hydrate for insomnia - low doses of benzodiazepines for anxiety are probably safe - parenteral nutrition if oral feeding is not possible - intravenous glucose (300 g/day) had been recommended in the past - intravenous heme: - 3-4 mg IV QD for 4 days - begin as soon as possible after attack - preparations: - hematin (Abbott) - heme albumin - heme arginate (Leiras Oy, Turka Finland) - heme albumin & arginate chemically stable & less likely than hematin to produce phlebitis or anticoagulant effect

Related

heme synthesis protoporphyrinogen IX protoporphyrinogen oxidase; PPO (PPOX) safe & unsafe drugs in acute intermittent porphyria (AIP), variegate porphyria (VP) & hereditary coproporphyria

General

porphyria

Properties

ACCUMULATION: PROTOPROPHYRINOGEN-IX DEFICIENCY: protoporphyrinogen oxidase

Database Correlations

OMIM correlations MORBIDMAP 600923

References

  1. Textbook of Biochemistry with Clinical Correlations, 3rd ed., TM Devlin (ed), Wiley-Liss, NY 1992 pg 1012
  2. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 172
  3. Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 260-62
  4. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 2076, 2078
  5. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 179