Diseases of Tetrapyrrole Metabolism - Refsum Disease and the Hepatic Porphyrias Medication
- Author: Norman C Reynolds, Jr, MD; Chief Editor: Stephen A Berman, MD, PhD, MBA more...
Two medical therapies are effective in aborting porphyric attacks: IV 10% dextrose in water (D10W) and IV hemin (ie, hematin). Experienced patients with porphyria consume foods high in sugar (eg, candy, ice cream) when they feel an impending attack. If anxious feelings are not episodic but chronic, low dose loxapine is helpful and safe on a regular basis. Injectable hemin (Panhematin) is now approved by the FDA for women with catamenial patterns of exacerbation.
Intravenous Nutritional Therapy
Glucose is used most commonly. The "glucose effect" reverses or aborts acute porphyric attacks by reducing the rate of porphyrin synthesis using normal endogenous energy metabolism. The "glucose effect" should be reserved for patients with mild pain and no paresis or as a stopgap measure while waiting for hematin.
Administered IV to hospitalized patients. Observe carefully for what can become a rapidly changing situation using the first of 2 inpatient drugs of choice. If therapeutic control lost, the patient is switched to IV hemin. Prior to admission, oral sugar loading can be tried. Standard solution is D10W.
Hemin[14, 15] (ie, hematin) infusion is designed specifically for use in reversing severe acute porphyric attacks. It is also indicated for women who experience recurring attacks associated with their menstrual cycles. After acute attacks are aborted, the hemin can be administered again, either weekly or monthly in the more refractory individuals, when pain complaints initiate a recurring attack.
Enzyme inhibitor derived from processed RBCs and iron-containing metalloporphyrin. Previously known as hematin, term used to describe chemical reaction product of hemin and sodium carbonate solution. Generally used as second DOC (to follow D10W unless prior use suggests that it is superior in a given patient, a patient is at risk for severe diabetic ketoacidosis, or initial D10W treatment fails to stabilize the acute porphyric episode within 2 d). Patients should be well hydrated to avoid (reversible) renal shutdown. "Glucose effect" should be tried initially if possible.
These agents control idiopathic seizures in patients with manifest porphyrias or in whom porphyric carrier status is suspected.
Has properties in common with other anticonvulsants, but most importantly is not metabolized in liver, which makes it safe for use in hepatic porphyrias.
Exact mechanism of action not known. Structurally related to GABA but does not interact with GABA receptors.
Used as adjunct therapy for partial seizures and myoclonic seizures. Also indicated for primary generalized tonic-clonic seizures. Mechanism of action is unknown.
These agents are useful in treating hepatic porphyrias, which are recurring anxious feelings not necessarily associated with impending porphyric attack.
Safety of medication use in hepatic porphyrias is key to maintaining health and avoiding attacks. Loxapine is well tolerated and useful for recurring anxious feelings common in porphyrias. Should be used for recurrent anxious feelings not associated with impending porphyric crisis. Treatment for the latter is noted under IV dextrose use and is initiated by using high oral sugar intake followed by IV dextrose in a hospital setting for close observation. Treatment for the former can be either low-dose maintenance or as needed.
Frank J, Christiano AM. Variegate porphyria: past, present and future. Skin Pharmacol Appl Skin Physiol. 1998 Nov-Dec. 11(6):310-20. [Medline].
Brenner DA, Bloomer JR. The enzymatic defect in variegate porphyria. Studies with human cultured skin fibroblasts. N Engl J Med. 1980 Apr 3. 302(14):765-9. [Medline].
Morais P, Mota A, Baudrier T, Trigo F, Oliveira JP, Cerqueira R, et al. Erythropoietic protoporphyria: a family study and report of a novel mutation in the FECH gene. Eur J Dermatol. 2011 Jul-Aug. 21(4):479-83. [Medline].
To-Figueras J, Ducamp S, Clayton J, Badenas C, Delaby C, Ged C, et al. ALAS2 acts as a modifier gene in patients with congenital erythropoietic porphyria. Blood. 2011 Aug 11. 118(6):1443-51. [Medline].
Wang Y, Langer NB, Shaw GC, Yang G, Li L, Kaplan J, et al. Abnormal mitoferrin-1 expression in patients with erythropoietic protoporphyria. Exp Hematol. 2011 Jul. 39(7):784-94. [Medline]. [Full Text].
Kohlschütter A, Santer R, Lukacs Z, Altenburg C, Kemper MJ, Rüther K. A Child With Night Blindness: Preventing Serious Symptoms of Refsum Disease. J Child Neurol. 2011 Dec 7. [Medline].
Sassa S. Modern diagnosis and management of the porphyrias. Br J Haematol. 2006 Nov. 135(3):281-92. [Medline].
Dragneva S, Szyszka-Niagolov M, Ivanova A, Mateva L, Izumi R, Aoki Y, et al. Seven Novel Mutations in Bulgarian Patients with Acute Hepatic Porphyrias (AHP). JIMD Rep. 2014 Jul 6. [Medline].
Marsden JT, Rees DC. Urinary excretion of porphyrins, porphobilinogen and d-aminolaevulinic acid following an attack of acute intermittent porphyria. J Clin Pathol. 2014 Jan. 67(1):60-5. [Medline].
Felsher BF, Norris ME, Shih JC. Red-cell uroporphyrinogen decarboxylase activity in porphyria cutanea tarda and in other forms of porphyria. N Engl J Med. 1978 Nov 16. 299(20):1095-8. [Medline].
Jiménez-Jiménez FJ, Agúndez JA, Martínez C, Navacerrada F, Plaza-Nieto JF, Pilo-de-la-Fuente B, et al. Hereditary Coproporphyria Associated with the Q306X Mutation in the Coproporphyrin Oxidase Gene Presenting with Acute Ataxia. Tremor Other Hyperkinet Mov (N Y). 2013. 3:[Medline]. [Full Text].
Reynolds NC Jr, Miska RM. Safety of anticonvulsants in hepatic porphyrias. Neurology. 1981 Apr. 31(4):480-4. [Medline].
Zadra M, Grandi R, Erli LC, et al. Treatment of seizures in acute intermittent porphyria: safety and efficacy of gabapentin. Seizure. 1998 Oct. 7(5):415-6. [Medline].
Anderson KE, Bloomer JR, Bonkovsky HL, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med. 2005 Mar 15. 142(6):439-50. [Medline].
Anderson KE, Collins S. Open-label study of hemin for acute porphyria: clinical practice implications. Am J Med. 2006 Sep. 119(9):801.e19-24. [Medline].
Brodie MJ, Thompson GG, Moore MR, et al. Hereditary coproporphyria. Demonstration of the abnormalities in haem biosynthesis in peripheral blood. Q J Med. 1977 Apr. 46(182):229-41. [Medline].
Eales L. The acute porphyria attack. 3. Acute porphyria: the precipitating and aggravating factors. S Afr Med J. 1971 Sep 25. 120-5. [Medline].
Goldberg A, Rimington C, Lochhead AC. Hereditary coproporphyria. Lancet. 1967 Mar 25. 1(7491):632-6. [Medline].
Hunter GH. Anesthetic considerations in hepatic porphyrias. CRNA. 1999 Feb. 10(1):6-14. [Medline].
Kappas A, Sassa S, Galbraith RA, et al. The porphyrias. Scriver CR, Beaudet AL, Sly WS, Valle D, ed. The Metabolic and Molecular Basis of Inherited Disease. New York: McGraw-Hill; 1995. 2103-2159.
King PH, Bragdon AC. MRI reveals multiple reversible cerebral lesions in an attack of acute intermittent porphyria. Neurology. 1991 Aug. 41(8):1300-2. [Medline].
Lazarow PB, Moser HW. Disorders of peroxisome biogenesis. Scriver CR, Beaudet AL, Sly WS, Valle D, ed. The Metabolic and Molecular Basis of Inherited Disease. New York: McGraw-Hill; 1995. 2287-2324.
Meyer UA, Schuurmans MM, Lindberg RL. Acute porphyrias: pathogenesis of neurological manifestations. Semin Liver Dis. 1998. 18(1):43-52. [Medline].
Redeker AG. Phlebotomy treatment of porphyria cutanea tarda: is it really effective?. Calif Med. 1969 Nov. 111(5):404-6. [Medline].
Tenhunen R, Mustajoki P. Acute porphyria: treatment with heme. Semin Liver Dis. 1998. 18(1):53-5. [Medline].
Verhoeven NM, Wanders RJ, Poll-The BT, et al. The metabolism of phytanic acid and pristanic acid in man: a review. J Inherit Metab Dis. 1998 Oct. 21(7):697-728. [Medline].