Variegate porphyria is an autosomal dominant genetic disease of heme metabolism in which partial or total protoporphyrin oxidase deficiency leads to cutaneous and neurological symptoms in childhood. The diagnosis is made by measuring the levels of this enzyme in feces, blood, or urine, while genetic testing is used for confirmation.
Together with hereditary coproporphyria (HCP), acute intermittent porphyria (AIP), and δ-aminolevulinic acid dehydratase porphyria (ADP), variegate porphyria (VP) belongs to the group of acute hepatic porphyrias, as mitochondrial protoporphyrin oxidase (PPOX), the enzyme affected in VP and necessary for the seventh step in heme synthesis, performs its respective function of converting protoporphyrinogen IX to protoporphyrin IX in the liver  . In VP, autosomal dominant gene mutations of the PPOX lead to its insufficient activity and the onset of cutaneous and neurovisceral symptoms   . Chronic blistering lesions in the form of erosions, bullae, and ulcerations with crusting and slow recovery are principal manifestations on the skin  . Lesions are usually seen in childhood on the hands and face  . The trauma of the skin that is exposed to sunlight seems to be the major risk factor for their appearance  . Hypertrichosis and either hyper or hypopigmentation, as well as thickening of the skin are other notable findings . On the other hand, vomiting, constipation, tachycardia, fever, fatigue, abdominal pain, muscle weakness, seizures, mental instability, paresis and neuromuscular deficits are hallmarks of an "acute neurovisceral attack" that is typical for patients suffering from VP   . Due to the fact that respiratory paralysis is a known complication, but also because the diagnosis is often delayed, a 10% mortality rate from acute attacks is observed  . Patients may exhibit either of the two types of symptoms or both, whereas growth retardation and significant developmental disturbances are seen in the rare homozygous forms of VP .
Early recognition of VP, particularly when patients develop neurovisceral attacks, can be life-saving, which is why a thorough workup is necessary. The first step is obtaining a detailed patient and family history, given the autosomal dominant nature of the disease. Furthermore, the population of Dutch descendants living in South Africa is at the greatest risk for developing VP due to the founder effect   . After history taking, the physical examination, if done properly, could identify typical skin lesions and assess their progression, thus a provisional diagnosis of VP can be made. Laboratory studies are the mainstay in diagnosing porphyrias, and the following tests should be implemented when a suspicion toward VP exists:
A definite diagnosis, however, is made after conducting genetic studies on the PPOX gene located on chromosome 1, or by detecting a lower PPOX activity in lymphocytes   .