Porphyria for the general physician

Abstract

Awareness and consideration are essential in making/suspecting a diagnosis of the acute neuropsychiatric porphyriasAcute porphyria should be considered in the differential diagnosis of hyponatraemia, renal impairment and atypical psychiatric and neurologic disorders Accurate quantitation of porphobilinogen, δ-aminolaevulinate and porphyrins in laboratory samples is essential in confirming a diagnosis Recent developments in treatment and prevention strategies have considerably improved the quality of life of patients with porphyria Molecular genetics are not necessary in initial diagnosis, but are valuable in confirmatory investigations and in family studiesAccurate biochemical diagnosis is crucial in cutaneous porphyria since acute porphyrias (variegate porphyria and hereditary coproporphyria) can cause skin signs indistinguishable from a non-acute porphyria (porphyria cutanea tarda) Porphyria cutanea tarda often reflects underlying liver disease or haemochromatosis Neuropsychiatric featuresThe acute porphyrias are also known as the neuropsychiatric porphyrias due to the neurological and occasional psychiatric features of a severe acute attack. Occasionally, patients with a primarily psychiatric diagnosis are referred for consideration of an underlying porphyria. 7 Because of the stigma associated with a psychiatric diagnosis, patients and their relatives prefer a diagnosis of porphyria to one of a primary psychosis. A careful study by Patience et al 8 indicated that, with the exception of anxiety disorder, schizophrenia, bipolar disorder and simple depression are no more common in the acute porphyrias than in a control population. The basis of the association of chronic anxiety with porphyria is unclear. Some studies consider it secondary to recurrent acute attacks but it is equally common in fully latent cases. The symptoms may be quite disabling and referral for assessment and treatment (eg cognitive behavioural therapy) can be helpful.A recent report has highlighted the important relationship between epilepsy and the acute porphyrias. 9 Screening testsPrevious laboratory screening tests for porphyria were unreliable with false-positive and false-negative rates approaching 50%. 10 More recent semiquantitative tests are more accurate, but a definitive conclusion requires quantitative assay for porphobilinogen (PBG) and δ-aminolaevulinic acid (ALA) in an early morning urine sample. 11 Certain drugs may interfere with screening tests, while assays of PBG alone may be unreliable in aged urine samples, may not reflect the clinical activity of the porphyria, would not identify Doss porphyria (due to PBG synthase defect) and may miss cases of secondary porphyria (eg lead poisoning). Renal complicationsRenal complications of acute porphyria are recognised in the porphyria literature but nephrologists rarely consider them in the differential diagnosis of chronic renal disease. A recent update series on renal failure in this journal failed to mention porphyria. 12 Hypertension and analgesic nephropathy are not infrequ...

Paralytic Ileus and Liver Failure—An Unusual Presentation of Advanced Erythropoietic Protoporphyria

“…EPP is a rare genetic disorder of heme metabolism caused by a deficiency of FECH, which catalyzes the last step of heme synthesis [16][17][18][19]. This defect leads to accumulation of protoporphyrin IX in erythrocytes, plasma, skin, and liver [3,5].…”

“…Erythropoietic protoporphyria (EPP) is an uncommon genetic disorder of heme metabolism caused by the deficiency of mitochondrial ferrochelatase, an enzyme that catalyzes the chelation of iron to protoporphyrin (PP) [1][2][3]. Skin involvement is the most typical feature of this disease.…”

Porphyrien

“…Aufgrund der manchmal verwirrenden und nicht eindeutigen Symptomatologie sowie der Seltenheit der einzelnen Subtypen ist die Diagnosestellung einer Porphyrie oftmals schwierig und mit einer variablen Latenzzeit verbunden [12] …”

Porphyria Cutanea Tarda

“…This condition causes fragility of sun-exposed skin, particularly on the backs of the hands and arms, sometimes accompanied by tense bullae, scarring, and altered pigmentation (Peters & Sarkany, 2005; Figure 1). …”

“…The lack of sufficient quantities of this enzyme leads to elevated porphyrin levels, in particular uroporphyrins (Miller & Saedi, 2007). The elevated iron levels also damage the liver and result in an increased risk of hepatocellular carcinoma (Peters & Sarkany, 2005). The incidence of porphyria cutanea tarda increases in summer months and positively correlates to sun exposure (Miller & Saedi, 2007).…”