Contact UPA at 800-868-1292 or info@porphyria.org
Stay connected to not miss out on our What’s UP, Doc? section. We will post a patient question along with a physician response. The response will come from an esteemed member of the UPA Scientific Advisory Board.
Do you have a question you would like to ask a Porphyria Expert? Send us an email at info@porphyria.org. We’d love to hear from you!
What’s UP Doc - Question of the week:
I heard a doctor in a presentation say that people with porphyria should “look after their kidneys.” How do you do that?
Response
This week our response was provided by Dr. Herbert Bonkovsky.
Persons with acute hepatic porphyries are at increased risk to develop chronic kidney disease. One likely cause of this is increased levels of ALA, which occur in some patients with AHPs.
Among other factors that can lead to chronic kidney damage are systemic arterial hypertension [high blood pressure], which should be looked for at least twice per year, such as during periodic visits with primary care providers. Many persons now have devices for monitoring BP. The idea is not more than 130/80 mmHg. Diabetes mellitus is another and major risk factor for development of chronic kidney disease, so avoiding obesity and avoiding foods with high glycemic indices are best. Avoidance of or prompt treatment of urinary tract infections is also important. Some medications can damage the kidneys and are better avoided if possible. For example amino glycoside antibiotics, chronic use of NSAIDs, chronic use of high doses of acetaminophen, which some patients take for chronic pain syndromes. Givosiran is known to lead to some adverse renal effects, so any patients chronically receiving givosiran should have urinalysis, urine protein and creatinine, and CMP with estimation of GFR performed at least every 6 months. If evidence of progressive increase in serum creatinine or urinary protein occurs, or decrease in eGFR, greater than 10% below baseline, additional evaluation should be undertaken by a medical kidney specialist [nephrologist].
To read more about Dr. Bonkovsky click here.
What’s UP Doc - Question of the week:
Can starting menopause make PCT worse/relapse? (because phlebotomies are a treatment and if you stop having periods maybe iron builds up?)
Response
This week our response was provided by Dr. Herbert Bonkovsky.
While what the writer asks is, perhaps, possible occasionally, in practice this had not proven to be much of a factor in increasing clinical features of PCT. In 50+ years of clinical practice, we have not encountered such an occurrence. More important risk factors for PCT are alcohol, hemochromatosis, chronic hepatitis C, and estrogen use. And treatment with low-dose hydroxychloroquine and/or therapeutic phlebotomies to keep serum ferritin within the range of 25-100 ng/mL are highly effective, regardless of menopausal status.
To read more about Dr. Bonkovsky click here.
What’s UP Doc - Question of the week:
I am thinking about starting Givlaari injections. What tests should I have done before and during my treatment?
Response
This week our response was provided by Dr. Bruce Wang of UCSF.
Prior to starting Givlaari: confirm AHP diagnosis both biochemically (urine ALA and PBG) and genetically. There should be multiple ALA and PBG results since patients should only consider Givlaari if they have experienced multiple acute attacks. This helps establish the patient’s own baseline as well as levels during attacks. Additional baseline tests before starting Givlaari include blood tests for liver function, creatinine and homocysteine.
Before each Givlaari injection (within a few days): urine test for ALA, PBG, and creatinine. The goal is to ensure that ALA and PBG are well controlled at the current Givlaari interval.
Other tests to consider while on Givlaari: Patients should be tested for liver function tests to look for liver toxicity, serum creatinine for renal toxicity, and homocysteine levels. The optimum frequency and intervals remain to be determined.
To read more about Dr. Wang click here.
What’s UP Doc - Question of the week:
I have Variegate Porphyria – why am I confused during an attack?
Response
This week our response was provided by Dr. Karl Anderson, Porphyria Expert at UTMB.
Confusion, and other symptoms, are all part of the neurological symptoms of AHP. We don’t really know the mechanism.
Read more about AHP here.
To learn more about participating in research so we can better understand the symptoms of an acute attack, please contact the UPA. We will connect you with a Porphyria Center.
To read more about Dr. Anderson click here.
What’s UP Doc - Question of the week:
I understand that Porphyria is a rare disease and being recently diagnosed with AIP, I am trying to understand more and more. How many people in the US have porphyria? Which type of porphyria is the most common? The least common? How do you calculate these numbers?
Response
For this week’s response, Dr. Brendan McGuire was able to answer a newly diagnosed patient’s question. We are lucky to have Dr. McGuire as a member of our Scientific Advisory Board.
Porphyria is a very rare group of diseases, with only a couple thousands of people affected in the United States. Porphyria Cutanea Tarda (PCT) was always considered the most common type, but with the benefit of medications to cure hepatitis C, the rates of PCT are declining. Currently Acute Intermittent Porphyria (AIP) is the most common type, while Aminoleuvulinic Acid Dehydratase (ALAD) Deficiency the least common. We use data collected from our longitudinal database to calculate these numbers. To get more accurate accounts we encourage all patients with porphyria to enroll in our longitudinal database or with the United Porphryias Association.
To enroll into the Longitudinal Study, contact us at 800.868.1291 so we can connect you with a Coordinator.
What’s UP Doc - Question of the week:
Can having tachycardia (fast, irregular heartbeat) due to AHP cause long term health issues? If you have tachycardia from ahp, are there things you can do to protect your heart?
Response
This week, Dr. Karl Anderson and Dr. Herbert Bonkovsky, both of the UPA Scientific Advisory Board and Porphyrias Consortium collaborated to answer this question.
Tachycardia refers only to a heart rate that is faster than normal. For example, it may accompany fever or dehydration, and is common during acute attacks of porphyria. Arrhythmia is the term reserved for a condition in which the heart rhythm is abnormal, either irregular or regular, most often due to a heart condition.
Most patients with AHPs experience tachycardia only during acute attacks, and it improves as the attack resolves. Arrhythmias are less common and may need further evaluation. If such attacks are treated promptly and with success, the long-term risk to the heart and cardiovascular system is slight or nil.
Most patients with recurrent or chronic tachycardia or arrhythmias do not suffer from AHP. Patients with AHPs and such problems are best evaluated and managed by a physician with expertise in the porphyrias and a cardiologist.
To read more about Dr. Anderson and Dr. Bonkovsky, click on their names.
What’s UP Doc - Question of the week:
What is the Porphyrias Consortium? Why is it so important? What do they do?
Response
This week our response was provided by Dr. Hetanshi Naik, who not only is a member of the Porphyrias Consortium, but also serves on UPA’s Board of Directors. To read more about Dr. Naik please click here.
The Porphyrias Consortium (PC) is a group of porphyria experts across the US who have come together and formed a group dedicated to improving patients’ lives by conducting research for all the porphyrias, as well as training new porphyria specialists. It is the first group of its kind dedicated solely to the porphyrias and the PC physicians and investigators work closely with the UPA. More information on the PC can be found on our website: https://www1.rarediseasesnetwork.org/cms/porphyrias/.
The currently ongoing studies that the PC is doing can be found here: https://www.porphyria.org/research/ongoing-research/. These studies are designed to help us learn more about the porphyrias or test certain treatments so we can better care for patients.
What’s UP Doc - Question of the week:
During a recent patient meeting, we received a question regarding enzymes and why they are important in the porphyrias. We developed an online module based on input from geneticists of the Porphyrias Consortium as a tool to explain. Please visit What is Porphyria? to access the module!
The porphyrias are a group of rare, genetic disorders. People living with a porphyria have changes to certain genes, called mutations, which affect their body’s ability to regulate itself. /p>
In the porphyrias, these mutations are in the genes involved in a certain chemical pathway, called the heme biosynthetic pathway. Heme is a compound that the body needs to make hemoglobin and there are several steps to make this compound in the body. Each type of porphyria is caused by a defect in a specific enzyme in the heme biosynthetic pathway. Without these enzymes working properly, the body is not able to finish making heme and it causes a buildup of other compounds, called porphyrins. It is the buildup of different types of porphyrins that causes the different types of porphyria and associated symptoms.
You may notice a similarity to the United Porphyrias logo!
What’s UP Doc - Question of the week:
Porphyria is a complex condition and it's hard for patients to put together a "team" of doctors to collaborate on our care, especially when we may not know the systems of our body to regularly monitor and evaluate. Can you recommend a list of specialties for acute porphyria patients, and a list of specialties for cutaneous porphyria patients?
Response
This week Dr. Bruce Wang helps patients as they try to assembler their “team” of doctors. To read more about Dr. Wangs suggested “team” of doctors for each porphyria click here.
To read more about Dr. Wang, click here.
What’s UP Doc - Question of the week:
What extra precautions should I take when I am having my teeth cleaned or any dental work? I have CEP and want to talk to my dentist in advance.
Response
This week, Dr. Angelika Erwin provided her response below.
It is important to discuss your condition with your doctor in advance of any dental care to ensure safety during your appointment.
Individuals with CEP have been reported to have thinner tooth enamel, which makes them more prone to developing cavities. Regular dental check-ups are therefore important. The grayish-brownish discoloration (erythrodontia) that is often present in CEP is caused by porphyrin deposition in the teeth. Teeth whitening is usually not effective in treating the discoloration and some patients decide to address this with veneers or crowns (only for cosmetic reasons).
The main concern is protecting you from fluorescent light during your appointment. In CEP, the skin is more sensitive to longer ultraviolet wavelengths (UVA) and to visible light. The most damaging wavelengths are between 400-410 nanometers since porphyrins are majorly activated in this range, with additional peaks described between 500-700 nanometers. To do this, the options include replacement of fluorescent lights with incandescent bulbs or installation of filtering screens in front of the bulbs.
Filters for lighting at your doctor’s office are recommended, just like filter films for windows at home and in the car. Filters can typically be attached to any necessary lighting.
Protection for your eyes from visible light is also very important to avoid corneal damage. Good quality sunglasses with UV protection are another option while having dental work.
Remember to schedule an annual exam to make sure you check your Calcium and Vitamin D levels, have an annual eye exam to assess any corneal involvement, and make an annual visit to monitor porphyrins, blood count and liver enzymes.
What’s UP Doc - Question of the week:
What should a person with Acute Hepatic Porphyria know about homosysteine and is there guidance for patients to follow?/p>
Response
This week, Dr. Manisha Balwani and Dr. John Phillips, wrote a joint response to this important question.
Homocysteine is an amino acid, a chemical your body uses to make proteins. Under normal conditions, vitamins B12, B6 and folate are used to process homocysteine to create other substances your body needs. When homocysteine is elevated it is called hyperhomocysteinemia and refers to an increased level of total homocysteine in the blood. Normal levels of total homocysteine are less than 15 µmol/L, mild elevations are >16-30 µmol/L, and severe homocysteine elevation is usually >100 µmol/L. Significantly elevated levels of homocysteine have been associated with increased risk for blood clotting, heart disease, as well as neurologic diseases. However, the clinical significance of mild to moderate increases in homocysteine levels are unclear.
Genetic disorders in the homocysteine metabolic pathways have been found and often lead to significant levels of homocysteine. Nutritional deficiencies of folate, vitamin B12, or vitamin B6 can also result in mild to moderate homocysteine elevations. These acquired conditions can easily be treated with vitamin supplementation of the lacking nutrient.
Increased levels of homocysteine have been reported in some patients with Acute Hepatic Porphyrias (AHP) with recurrent attacks as well as some patients with high levels of ALA and PBG without active clinical symptoms. In some of these cases, patients also had low levels of vitamin B6. Homocysteine levels were shown to be higher in AHP patients with active clinical symptoms.
In clinical trials with AHP patients on Givosiran, it was noted that some of the Givosiran treated patients had elevated levels of homocysteine, although levels before treatment were not available for comparison. Other studies showed that Givosiran increased homocysteine levels in Acute Intermittent Porphyria (AIP) patients compared to pre-Givosiran treatment. Most patients had mild to moderate increases in homocysteine and some patients also had low levels of vitamin B6 and folate. Supplementing vitamin B6 in these patients resulted in a decrease or normalization of homocysteine levels.
Given this, monitoring of total homocysteine levels is recommended for AHP patients. Patients on Givosiran should have levels checked before and during treatment since levels can fluctuate over time. It is also important to monitor levels of vitamin B6, B12 and folate in AHP patients, particularly those on Givosiran. Patients with significantly increased levels (homocysteine >100 µmol/L) should receive vitamin B6 supplementation. This can also be considered in patients with moderately high levels of homocysteine. The clinical implications the increase in homocysteine in patients on Givosiran is unknown and needs to be monitored long term. As we increase our knowledge through long term follow up of patients, these recommendations may change over time.
Ventura P, Corradini E, Di Pierro E, Marchini S, Marcacci M, Cuoghi C, Buzzetti E, Pietrangelo A. Hyperhomocysteinemia in patients with acute porphyrias: A potentially dangerous metabolic crossroad? Eur J Intern Med. 2020 Sep;79:101-107
Vassiliou D, Sardh E. Homocysteine elevation in givosiran treatment: Suggested ALAS1 siRNA effect on cystathionine beta-synthase. J Intern Med. 2021 Oct;290(4):928-930.
Fontanellas A, Ávila MA, Arranz E, Enríquez de Salamanca R, Morales-Conejo M. Acute intermittent porphyria, givosiran, and homocysteine. J Inherit Metab Dis. 2021 Jul;44(4):790-791
To-Figueras J, Wijngaard R, García-Villoria J, Aarsand AK, Aguilera P, Deulofeu R, Brunet M, Gómez-Gómez À, Pozo OJ, Sandberg S. Dysregulation of homocysteine homeostasis in acute intermittent porphyria patients receiving heme arginate or givosiran. J Inherit Metab Dis. 2021 Jul;44(4):961-971
To read more about Dr. Balwani, click here. To read more about Dr. Phillips, click here.
What’s UP Doc - Question of the week:
A lot of EPP patients are confused about taking iron supplements. What would you suggest?
Response
This question was sent with the request of a response from Amy Dickey, MD:
A big reason that EPP patients are confused about this topic is that doctors are confused about this too. This is a hard question, and there are experts who have different opinions about this. Some studies point in one direction, and others point in the opposite. The answer also depends on each patient’s individual clinical situation. Most importantly, the answer depends on if you have typical EPP that is caused by genetic mutations in the enzyme FECH or if you have X-linked protoporphyria (XLP) caused by a genetic mutation in a different enzyme ALAS2. Both EPP and XLP patients have the same symptoms and have same/similar blood test findings. The main way to tell them apart is by genetic testing.
Iron supplements are helpful for patients with XLP who have iron-deficiency and/or anemia. This is because iron can actually make the problematic enzyme ALAS2 more normal in people with XLP. For patients with typical EPP, though, the answer is more complicated and confusing. On the one hand, iron could tell your body to make more red blood cells, and this increase will also increase protoporphyrin, which is the substance in the blood that causes painful light sensitivity in EPP. We want to avoid that. While this happens to some extent, it seems that the protoporphyrin will go back to baseline after some time. On the other hand, iron could help get of rid of some protoporphyrin by turning it into heme. That’s actually what the enzyme FECH does; it puts iron into protoporphyrin making heme. A higher percentage of EPP patients have iron deficiency than in the general population.
However, it’s not clear why, and it’s also not clear if and to what extent this is causing a problem. There are certainly other things that can cause anemia and iron deficiency in patients with EPP, such as blood loss from something else. Iron deficiency and anemia can make people feel really bad. It can make people very tired and short of breath, and it can even have negative effects on the heart, skin, hair, and mood. Because of that, it’s recommended to give iron supplements to people with EPP if there is iron deficiency, anemia, and symptoms from it. If people have really high protoporphyrin and signs of liver damage, though, treating iron deficiency is likely more risk than it’s worth. Exactly where the risk-benefit line is for treating iron deficiency is not too clear, and each patient’s situation is different. It’s important to talk with your doctor about this. Iron isn’t always bad or always good for patients with EPP. For what it’s worth, I have EPP and take iron supplements myself, so I do think iron supplements have some role in EPP care.
To read more about Dr. Dickey, click here.
What’s UP Doc - Question of the week:
United Porphyrias has received many questions about pain, most related to pain in the Acute Hepatic Porphyrias (AIP, VP, HCP, ADP). This week, we are addressing Pain in Acute Hepatic Porphyria in depth.
Response
We sought the pain management expertise of neurologist and porphyria specialist, Dr. Mohamed Kazamel who has provided the attached publication with the support of his porphyria expert peers. Click here to read more.
To read more about Dr. Kazamel, click here.
What’s UP Doc - Question of the week:
Last week, a mom asked about her son and his liver. He had EPP. My daughter (now age 26) has AIP and I have a similar question about the health of her liver. How will acute porphyria attacks impact her liver as she ages? She was diagnosed a few years ago and her last attack was several months ago. I appreciate your response.
Response
Thank you so much for the wonderful follow up question. UPA Scientific Advisory Board member Dr. Herbert L. Bonkovsky provided his response below.
“Most patients with AIP have normal or near-normal livers and they do not suffer from progressive liver disease or its complications. However, there is a modestly increased risk of their developing chronic liver disease and primary liver cancer [hepatocellular carcinoma, HCC], especially with advancing age. The risks of these disorders are likely greater among patients with biochemically active AIP: those who chronically over produce and over-excrete delta-aminolevulinic acid [ALA] and porphobilinogen [PBG]. It seems likely that the chief potential toxic intermediate is ALA, which causes increased oxidative stress.
We recommend that patients with AIP take good care of their livers: they should receive vaccinations to protect them from developing hepatitis A and B, for which there are safe and effective vaccines; they should not drink alcohol to excess—for women this means not more than one drink per day; for men, not more than two. They should avoid obesity and hyperlipidemia, both of which are associated with fatty liver disease, as is excess alcohol. Drugs and herbals and dietary supplements, especially concentrated extracts of green tea, are also hepatotoxic in some susceptible persons, so we recommend caution in their use and only for clearly indicated medical reasons, not for purposes of 'general health' or for 'weight loss.' Keeping other approved vaccinations complete and up-to-date, such as DPT, HPV, yearly flu, Covid-19 with boosters, etc, is strongly recommended.
Acute porphyric attacks should be treated promptly and vigorously, as recommended in our general guidelines:
It is good medical practice for AIP patients to have yearly tests of hepatic and kidney status with comprehensive metabolic panels. If there are abnormalities detected, further assessments by hepatologists and/or nephrologists with knowledge of AIP are likely indicated. Beginning at age 50 years, we recommend regular and ongoing screening for the development of HCC with liver ultrasound, CT, or MRI every 6 months. Fortunately, if HCC develop in patients with AIP and it, they are detected early, before they have become very extensive or have spread to other organs, they generally can be removed surgically with good long-term survivals.
To read more about Dr. Bonkovsky, click here.
What’s UP Doc - Question of the week:
My son has Porphryia and one question I ask myself and have had others ask me when telling them about EPP is:
We know what the extra porphyrins are doing when they have a reaction, and it makes their skin hurt but are they doing any damage on the inside of the body? For example, my mom always thought that if Mitchell was out in the sun and had an “attack” it would hurt his liver, but I know of other people with EPP that avoid light altogether and had their liver fail.
Response
Thanks for asking this question! Here is a detailed response from UPA Scientific Advisory Board member Dr. Amy Dickey, Porphyria Expert (Massachusetts General Hospital (MGH) and an Instructor of Medicine at Harvard Medical School (HMS):
“This is an incredibly important topic for patients with EPP like me. The short answer is no, light exposure does not increase an EPP patient’s risk of liver disease. Why is that? In EPP, a substance called protoporphyrin is made in the bone marrow and builds up in the body, especially in the blood. It gets deposited in the skin, and it is excreted in the stool after being filtered through the liver. The protoporphyrin in the skin reacts with light and causes internal damage and skin pain. The light is reacting with protoporphyrin that is already sitting in the skin and the small blood vessels in the skin, and light does not increase the levels of protoporphyrin. Separately from what is happening at the skin, protoporphyrin can get clogged in the liver ducts, causing liver injury and liver failure. Because light does not affect the amount of protoporphyrin in the body, it doesn’t change the risk of protoporphyrin getting clogged in the liver ducts. Some people with EPP have really high levels of protoporphyrin all the time, for reasons nobody understands. As compared to other EPP patients, these people are more likely to have liver failure and they’re also more likely to be especially sensitive to light. That being said, light exposure and painful EPP reactions isn’t what is causing liver damage in these patients.
One reason this topic maybe confusing to people is that in other types of porphyria, like acute intermittent porphyria (AIP), damaging substances called porphyrins and porphyrin precursors can increase in the body because of stress, certain medications, and other factors. The levels of these substances may otherwise be normal. In EPP, though, that doesn’t happen, and protoporphyrin levels are increased to about the same levels throughout a person’s life. Light doesn’t change them.
Light exposure in EPP is extremely painful and causes skin damage that can sometimes leads to permanent scarring. Otherwise, light exposure isn’t dangerous in EPP. As an EPP patient who has experienced the severe pain of EPP reactions, it’s really hard for me to completely believe that too much light exposure couldn’t somehow kill me. However, as a doctor and a researcher I know that this isn’t possible. There’s also no reason to think that light causes damage anywhere else besides the skin in EPP.”
To read more about Dr. Dickey, click here.
What’s UP Doc - Question of the week:
Hi, I was diagnosed with acute intermittent porphyria about two years ago. I’m always worried about my next attack. What plan should I have in place in the event of another attack? At what point do you think I shouldn’t try to go it alone without help?
Response
Thank you for your question! According to Dr. Karl Anderson, Porphyria Expert (University of Texas Medical Branch, Galveston, TX) here are the main items you should have in place. Remember to reach out to the UPA if you need support!
