The most common type of Porphyria in South Africa is Variegate Porphyria.
The History of the South African Porphyrias
Genealogical studies carried out suggested that the gene for the South African form of variegate porphyria was introduced into South Africa in 1688, when two Dutch settlers, Gerrit Jansz van Deventer and Adriaantje Ariens married in Cape Town.
A proven and interesting fact to note, most South African patients carry a single founder mutation, and haplotype analysis of the ancestral chromosomes has confirmed a relationship with Dutch families with variegate porphyria. In the years following 1688 the gene spread widely through the South African population and is common amongst South Africans of Dutch ancestry, whatever their race or home language.
The Enzyme Defect
The defective enzyme is protoporphyrinogen oxidase, which is responsible for the conversion of protoporphyrinogen to protoporphyrin. The defect results in the accumulation of large amounts of protoporphyrin and coproporphyrin, which are typically detectable in faecal samples.
Accumulation of these porphyrins in the skin is responsible for skin manifestations. When the haem synthetic pathway is stressed, the precursors ALA and PBG may also accumulate. This is associated with the onset of the acute attack.
The Genetic Defect
Both males and females are equally affected, and offspring of an affected parent have a 50% chance of inheriting the defective enzyme. Throughout the world, over 100 mutations have been shown to result in defective protoporphyrinogen oxidase activity and variegate porphyria.
The R59W Mutation
One mutation, namely the R59W mutation, represents the founder mutation in the South African population, and accounts for approximately 95% of all patients with variegate porphyria in South Africa. Testing for the R59W mutation is therefore a useful diagnostic test in the South African population. At least nine other mutations are found in South Africa. Families carrying these mutations test negative for the R59W mutation, and are not related to the large family descended from the original Dutch settlers.
Clinical Effects
Patients with variegate porphyria may experience both skin manifestations of the disease and the neurological which cause the acute attacks.
Homozygous Variegate Porphyria Four cases (two of whom are sisters) have been described in South Africa. All inherited the R59W mutation from one parent and a second, unrelated mutation from the other parent and are therefore compound heterozygotes. Two are extremely severely affected with photosensitivity from birth and neurological and skeletal developmental abnormalities including severe brachydactyly. The other two patients are less affected, but have unusually severe photosensitivity and the same characteristic abnormalities of the fingers though to a lesser degree.
The Diagnosis
The following tests alone or in combination are suitable for the diagnosis of variegate porphyria:
Positive plasma fluorescence peak at 625 nm on plasma fluoroscanning
Unequivocal elevation of stool coproporphyrin and protoporphyrin
Demonstration of a VP-associated mutation in the gene for protoporphyrinogen oxidase (typically the R59W mutation).
Therapy Therapy is directed towards amelioration of the skin disease , avoidance of precipitants of the acute attack and rapid and effective intervention for the established acute attack.
Drug Precautions
Full drug precautions are necessary as patients are at risk of the acute attack and a database exists whereby medications deemed safe, unsafe and those not proven either way are noted.
Footnote: There is no cure for Variegate Porphyria, it is one of the acute hepatic porphyrias, meaning that the liver is involved. Treatment is aimed at limiting or avoidance of triggers that precipitate an acute attack such as medicinal drugs, alcohol, smoking, dieting, fasting, environmental factors, chemicals, stress, UV light, the sun and fluorescent light amongst many others.
Treatment aimed at preventing attacks or lessening the severity include a diet high in carbohydrates, glucose, eating regular small meals.
My personal experience: Its not always easy to avoid triggers and not every trigger necessarily ends in an acute attack. There are symptoms that I have noted over the years that often make daily life challenging. They are not always debilitating enough that one cant continue with day to day tasks, just present enough to always niggle at the back of your mind.
The brain fog is ever present and always has been even from childhood, later in life I have found it is helped somewhat by certain prescribed medication to manage this. It helps .....yes.....but it never completely goes away. Its ever present like a menacing dark cloud that no matter how hard you try to visually move this away, so that you can see clearly on the other side it never moves. Sometimes it will tease you, move just enough to give that little glimmer of hope, the fog lifts just that bit.... you hope and pray it will move a little more but it never does. The next day its back in full force again. The anxiety, that is also ever present, though that only got much worse in my late teens. That is also helped somewhat by medication but again its always there. Anxiety....its crippling if you allow it to be, so you fight it to get through the day, some days the fight is worse but still its another piece of the puzzle. Then there is the mental fatigue, fighting ones demons daily is draining, both mentally and physically exhausting. The thing is you don't know any different. There are a few days in a month where I wake up feeling somewhat "Normal" and boy how other folk take normal for granted, the brain fog isn't as bad, the anxiety is manageable and you actually feel like you have beaten this only for it to hit you with a vengeance when it returns and it always does.
Restless legs, insomnia, some nights you fall into bed, you are tired so sleep should come easily.....not so, toss and turn, then the legs are uncomfortable, so you move constantly to get a good position to lie in. Then the room is too hot, then too cold, blankets feel to heavy so off go the covers, then you feel to exposed and on they come again.... night after night.
Then there are the headaches, again almost every day. Some days worse than others but still ever present. The nausea that wakes you up in the night or early hours of the mornings, you just keep trying to tell it to go away in your head and hallelujah it does but its only temporary. It will return again as sure as the sun will rise tomorrow.
The eyes, oh yes even the eyes. They are very sensitive to light, even on overcast days. Our eyes can sustain nerve damage amongst other potential afflictions too. My skin, oh dear how that itches and burns, from stress, from lighting, all I know is the scars I have from the constantly itching skin is enough to make one crazy, that and the skin infections!
I am not going to bore you with much more of this suffice to say that every single organ in the human body is affected by the acute Porphyria's, all this from one defective little enzyme, the liver, the kidneys, the skin, the neurological aspects, the gastrointestinal, the nervous system....ok you get the picture.
Its not a pity party but suffice to say this is a very misunderstood disease, many medical practitioners have never heard of Porphyria and some have a limited understanding of the full impact of this disease not forgetting that there are 8 different types of Porphyria and only a handful of those fall into the acute types. I myself pushed this disease to the back of my mind, I didn't educate myself enough either on my own disease until now later in life but sadly much of the damage has been done already.
By Lynn Croker
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