Acute porphyrias in the USA: Features of 108 subjects from porphyrias consortium

Herbert L. Bonkovsky, Vinaya C. Maddukuri, Cemal Yazici, Karl Anderson, D. Montgomery Bissell, Joseph R. Bloomer, John D. Phillips, Hetanshi Naik, Inga Peter, Gwen Baillargeon, Krista Bossi, Laura Gandolfo, Carrie Light, David Bishop, Robert J. Desnick

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Methods Between September 2010 and December 2012, 108 subjects with acute porphyrias (90 acute intermittent porphyrias, 9 hereditary coproporphyrias, 9 variegate porphyrias) were enrolled into an observational study. Genetic testing was performed at a central genetic testing laboratory and clinical information entered into a central database. Selected features were compared with data for adults in the US.

Results Most subjects (88/108, 81%) were female, with self-reported onset of symptoms in the second through fourth decades of life. The most common symptom was abdominal pain. Appendectomies and cholecystectomies were common before a diagnosis of porphyria. The diagnosis was delayed by a mean of 15 years. Anxiety and depression were common, and 18% complained of chronic symptoms, especially neuropathic and other pains. The incidences of systemic arterial hypertension, chronic kidney disease, seizure disorders, and psychiatric conditions were markedly increased. Mutations of the known causative genes were found in 102/105 of those tested, with novel mutations being found in 37, including in 7/8 subjects with hereditary coproporphyria. Therapy with intravenous hematin was the most effective therapy both for treatment of acute attacks and for prevention of recurrent attacks.

Conclusions Acute porphyrias often remain undiagnosed for more than a decade after first symptoms develop. Intravenous hematin is the treatment of choice, both for treatment of acute attacks and for prevention of recurrent attacks.

Background Recent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical, and genetic features of 108 subjects.

Original languageEnglish (US)
Pages (from-to)1233-1241
Number of pages9
JournalAmerican Journal of Medicine
Volume127
Issue number12
DOIs
StatePublished - Dec 1 2014

Fingerprint

Acute Intermittent Porphyria
Porphyrias
Hereditary Coproporphyria
Hemin
Genetic Testing
Variegate Porphyria
Therapeutics
Mutation
Appendectomy
Delayed Diagnosis
Cholecystectomy
Neuralgia
Chronic Renal Insufficiency
Abdominal Pain
Observational Studies
Psychiatry
Molecular Biology
Epilepsy
Anxiety
Databases

Keywords

  • Acute intermittent porphyria
  • Clinical features
  • Delta-aminolevulinic acid
  • Hematin
  • Heme
  • Hereditary coproporphyria
  • Hydroxymethylbilane synthase
  • Porphobilinogen
  • Porphobilinogen deaminase
  • Porphyrins
  • Variegate porphyria

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bonkovsky, H. L., Maddukuri, V. C., Yazici, C., Anderson, K., Bissell, D. M., Bloomer, J. R., ... Desnick, R. J. (2014). Acute porphyrias in the USA: Features of 108 subjects from porphyrias consortium. American Journal of Medicine, 127(12), 1233-1241. https://doi.org/10.1016/j.amjmed.2014.06.036

Acute porphyrias in the USA : Features of 108 subjects from porphyrias consortium. / Bonkovsky, Herbert L.; Maddukuri, Vinaya C.; Yazici, Cemal; Anderson, Karl; Bissell, D. Montgomery; Bloomer, Joseph R.; Phillips, John D.; Naik, Hetanshi; Peter, Inga; Baillargeon, Gwen; Bossi, Krista; Gandolfo, Laura; Light, Carrie; Bishop, David; Desnick, Robert J.

In: American Journal of Medicine, Vol. 127, No. 12, 01.12.2014, p. 1233-1241.

Research output: Contribution to journalArticle

Bonkovsky, HL, Maddukuri, VC, Yazici, C, Anderson, K, Bissell, DM, Bloomer, JR, Phillips, JD, Naik, H, Peter, I, Baillargeon, G, Bossi, K, Gandolfo, L, Light, C, Bishop, D & Desnick, RJ 2014, 'Acute porphyrias in the USA: Features of 108 subjects from porphyrias consortium', American Journal of Medicine, vol. 127, no. 12, pp. 1233-1241. https://doi.org/10.1016/j.amjmed.2014.06.036
Bonkovsky, Herbert L. ; Maddukuri, Vinaya C. ; Yazici, Cemal ; Anderson, Karl ; Bissell, D. Montgomery ; Bloomer, Joseph R. ; Phillips, John D. ; Naik, Hetanshi ; Peter, Inga ; Baillargeon, Gwen ; Bossi, Krista ; Gandolfo, Laura ; Light, Carrie ; Bishop, David ; Desnick, Robert J. / Acute porphyrias in the USA : Features of 108 subjects from porphyrias consortium. In: American Journal of Medicine. 2014 ; Vol. 127, No. 12. pp. 1233-1241.
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abstract = "Methods Between September 2010 and December 2012, 108 subjects with acute porphyrias (90 acute intermittent porphyrias, 9 hereditary coproporphyrias, 9 variegate porphyrias) were enrolled into an observational study. Genetic testing was performed at a central genetic testing laboratory and clinical information entered into a central database. Selected features were compared with data for adults in the US.Results Most subjects (88/108, 81{\%}) were female, with self-reported onset of symptoms in the second through fourth decades of life. The most common symptom was abdominal pain. Appendectomies and cholecystectomies were common before a diagnosis of porphyria. The diagnosis was delayed by a mean of 15 years. Anxiety and depression were common, and 18{\%} complained of chronic symptoms, especially neuropathic and other pains. The incidences of systemic arterial hypertension, chronic kidney disease, seizure disorders, and psychiatric conditions were markedly increased. Mutations of the known causative genes were found in 102/105 of those tested, with novel mutations being found in 37, including in 7/8 subjects with hereditary coproporphyria. Therapy with intravenous hematin was the most effective therapy both for treatment of acute attacks and for prevention of recurrent attacks.Conclusions Acute porphyrias often remain undiagnosed for more than a decade after first symptoms develop. Intravenous hematin is the treatment of choice, both for treatment of acute attacks and for prevention of recurrent attacks.Background Recent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical, and genetic features of 108 subjects.",
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AU - Anderson, Karl

AU - Bissell, D. Montgomery

AU - Bloomer, Joseph R.

AU - Phillips, John D.

AU - Naik, Hetanshi

AU - Peter, Inga

AU - Baillargeon, Gwen

AU - Bossi, Krista

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N2 - Methods Between September 2010 and December 2012, 108 subjects with acute porphyrias (90 acute intermittent porphyrias, 9 hereditary coproporphyrias, 9 variegate porphyrias) were enrolled into an observational study. Genetic testing was performed at a central genetic testing laboratory and clinical information entered into a central database. Selected features were compared with data for adults in the US.Results Most subjects (88/108, 81%) were female, with self-reported onset of symptoms in the second through fourth decades of life. The most common symptom was abdominal pain. Appendectomies and cholecystectomies were common before a diagnosis of porphyria. The diagnosis was delayed by a mean of 15 years. Anxiety and depression were common, and 18% complained of chronic symptoms, especially neuropathic and other pains. The incidences of systemic arterial hypertension, chronic kidney disease, seizure disorders, and psychiatric conditions were markedly increased. Mutations of the known causative genes were found in 102/105 of those tested, with novel mutations being found in 37, including in 7/8 subjects with hereditary coproporphyria. Therapy with intravenous hematin was the most effective therapy both for treatment of acute attacks and for prevention of recurrent attacks.Conclusions Acute porphyrias often remain undiagnosed for more than a decade after first symptoms develop. Intravenous hematin is the treatment of choice, both for treatment of acute attacks and for prevention of recurrent attacks.Background Recent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical, and genetic features of 108 subjects.

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KW - Porphobilinogen deaminase

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KW - Variegate porphyria

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