Journal of Postgraduate Medicine
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Year : 2013  |  Volume : 59  |  Issue : 3  |  Page : 241-242  

Challenges in the diagnosis and treatment of a case of acute intermittent porphyria in India

RV Dosi, AP Ambaliya, RD Patell, NN Sonune 
 Department of Medicine, Government Medical College and S.S.G. Hospital, Vadodara, Gujarat, India

Correspondence Address:
R V Dosi
Department of Medicine, Government Medical College and S.S.G. Hospital, Vadodara, Gujarat
India




How to cite this article:
Dosi R V, Ambaliya A P, Patell R D, Sonune N N. Challenges in the diagnosis and treatment of a case of acute intermittent porphyria in India.J Postgrad Med 2013;59:241-242


How to cite this URL:
Dosi R V, Ambaliya A P, Patell R D, Sonune N N. Challenges in the diagnosis and treatment of a case of acute intermittent porphyria in India. J Postgrad Med [serial online] 2013 [cited 2021 Nov 28 ];59:241-242
Available from: https://www.jpgmonline.com/text.asp?2013/59/3/241/118056


Full Text

A 16-year-old girl presented with a 4-month history of severe abdominal pain, low-grade fever, gradually progressive quadriparesis, and "spells" of altered behavior and confusion lasting from hours to days. She had been admitted to other hospitals and despite being investigated and imaged (including a computed tomography scan of the abdomen, a magnetic resonance imaging of the brain and a cerebrospinal fluid examination) her symptoms and signs progressed and were unexplained. Reddish urine had been noted, but testing for hematuria was negative. Physical examination showed marked wasting and areflexia of all four limbs and a normal abdomen. The urine was noted to have a reddish hue, and darkened when left in the sun for several hours [Figure 1]. A urine sample was positive for porphobilinogen (PBG) by a qualitative test (column chromatography). Electrophysiological studies demonstrated an axonal neuropathy. The marked elevation in PBG confirmed a diagnosis of an acute porphyria, the most common of which is acute intermittent porphyria (AIP). Confirmation of the type of acute porphyria requires additional biochemical and genetic testing not readily available in India. Treatment with hemin is the most effective treatment for porphyria attacks, [1],[2] but is also not readily available in India. Four ampoules of heme arginate (Normosang™, Orphan Europe) were imported urgently for this patient, despite financial and bureaucratic hurdles. The patient improved by the 2 nd day of treatment with hemin (3 mg/kg body weight by vein daily for 4 days), and with avoidance of exacerbating factors recovered sufficiently to restart school 6 months later.{Figure 1}

The porphyrias are a group of rare inherited metabolic disorders of heme biosynthesis leading to overproduction of heme precursors and a variety of non-specific clinical features. [1] Some porphyrias cause photosensitivity, but AIP presents exclusively with neurological symptoms that develop after puberty, including abdominal pain. Certain drugs, steroid hormones, alcohol, and reduced food intake are among the factors that can provoke attacks of AIP. It is likely that empiric use of harmful drugs (including diclofenac, metronidazole, diazepam, and phenytoin) in the absence of a specific diagnosis and reduced food intake contributed to progression of the disease in this patient.

None of the clinical findings including reddish to dark-brown discoloration of urine, often described as "port wine" red, [1] is specific for the acute porphyrias, but it can suggest the diagnosis. Darkening of the urine on exposure to sunlight is also not a specific finding. However, biochemical testing showing a substantial increase in PBG is a simple, sensitive, and specific method for diagnosis of the three most common acute porphyrias, including AIP. Although, PBG and its precursor delta-aminolevulinic acid (ALA, also elevated in AIP) are colorless, PBG degrades to form porphobilin, which is a brownish product; by a process accentuated by exposure to light. Urinary porphyrins, which are reddish in color, are also increased in AIP.

Finding a substantially increased urinary PBG in a spot sample is a rapid and sensitive method that establishes a diagnosis of acute porphyria as the cause of concurrent symptoms. [2] Because the porphyrias that elevate PBG (AIP, hereditary coproporphyria and variegate porphyria) are treated identically during attacks, treatment can be started once a substantial increase in urinary or plasma PBG is documented while further biochemical testing, including measurement of porphyrins in plasma, urine, and feces, and erythrocyte PBG deaminase activity is in progress. DNA testing to identify the causative mutation is also indicated to confirm the diagnosis.

Intravenous hemin and avoidance of contraindicated drugs and other harmful factors are the mainstay of management of AIP. [1],[2],[3] Hemin represses hepatic ALA synthase, the initial and rate-limiting enzyme of the heme synthetic pathway, thus reducing the overproduction of ALA, PBG and porphyrins by the liver. Procuring hemin in a third world country is a herculean task. Hemin is an orphan product manufactured in Europe (heme arginate) and the United States (hematin). We contacted the European manufacturer and were required to raise about 2 lakh rupees, and obtain special permission from the Customs and the Central Drugs Standard Control Organization on an urgent basis. This was accomplished by telephone with the cooperation of the concerned authorities within a few days and the first dose of the drug was obtained and administered about 2 weeks after the diagnosis.

This case illustrates that an accurate diagnosis of AIP can lead to proper management including specific treatment and a favorable outcome. A high index of suspicion is needed to suspect the disease, but the diagnosis is readily established by testing for increased PBG.

References

1Puy H, Gouya L, Deybach JC. Porphyrias. Lancet 2010;375:924-37.
2Anderson KE, Bloomer JR, Bonkovsky HL, Kushner JP, Pierach CA, Pimstone NR, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005;142:439-50.
3Harper P, Wahlin S. Treatment options in acute porphyria, porphyria cutanea tarda, and erythropoietic protoporphyria. Curr Treat Options Gastroenterol 2007;10:444-55.

 
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