Friday, October 30, 2015

Thursday, October 29, 2015

DNA Diagnosis of Porphyria- Important Clarifications by: Robert Desnick, M.D., PhD

DNA Diagnosis of Porphyria- Important Clarifications  
by:  Robert Desnick, M.D., PhD. 

 It has come to our attention that some Porphyria patients have sent their DNA to 23andMe or to other commercial companies, and have gotten results suggesting that they have “DNA confirmed Porphyria”. We are concerned that results from companies other than DNA testing laboratories that have experience in diagnosing porphyrias may provide patients with misleading information.

A major issue with DNA testing is whether a gene alteration (variant or mutation) is pathogenic (disease-causing) or benign (a change in the gene that does not cause or make one at-risk for the disease). For example, 23andMe does NOT do gene sequencing, but does determine if you have various gene alterations in the porphyria genes, all 57 of which are benign, and are not disease-causing but occur in a particular gene in which other lesions are in fact disease-causing. The benign lesions usually are identified by an “#rs” number. These benign changes are quite common but may lead a patient to believe that he/she has one or more porphyrias. They do not affect the heme biosynthetic enzymes, as they are not pathologic lesions. Of the gene lesions that cause disease, over 98% would be identified by gene sequencing as is done for all the Porphyrias at the Mount Sinai Laboratory and four Porphyrias at the Mayo Laboratory.

The Mount Sinai Genetic Testing Laboratory provides Porphyria DNA testing for all eight Porphyrias, and has a full-time Porphyria Genetic Counselor, Dana Doheny, MS, who is available to assist in arranging testing and interpreting the results. Typical time from receipt of sample to result is about two weeks. If the patient has “biochemical-positive” results and a DNA alteration cannot be found, there is a 1-2% chance that the patient has a “cryptic” mutation or a large deletion in the porphyria gene that is difficult to find by sequcning. The Mount Sinai Laboratory will do additional analyses to find the Porphyria gene lesion, if the patient has one. 

Mayo Laboratories test for only three of the four Acute Porphyrias and for Erythropoietic Protoporphyria. To our knowledge they provide sequence results, and do not report polymorphisms..

Desiree notes: Dr Desnick is one of the most famous genetisists in the world.  In fact, he is one of  only three board certified in the US.  See what he has to say about 23 and me. etc.

Monday, October 26, 2015

A Microbiologist Recreated 'Starry Night' With Bacteria In A Petri Dish And it's not too shabby.

Tuesday, October 20, 2015

Frequently asked questions about Porphyria!

Frequently Asked Questions

General Questions:

How does one get porphyria?
Most porphyrias are inherited.  However, one type, Porphyria Cutanea Tarda (PCT), may either be inherited (also referred to as “familial”) or “sporadic” due to various environmental factors.  In each type of porphyria there is a deficiency of a specific “enzyme”.  These enzymes are involved in the synthesis of “heme”, a substance important to many body functions and are found in large amounts in bone marrow and red blood cells (which contain hemoglobin), and also has an important function in the liver and muscles. The type of porphyria present is determined by which enzyme is deficient; these enzyme deficiencies are usually inherited. Environmental factors, such as drugs, chemicals, diet, and sun exposure can, depending on the type of porphyria, greatly influence the severity of symptoms.
How are the porphyrias inherited?  Can my children inherit porphyria from me?
The inherited porphyrias are either autosomal dominant (inherited from one parent), autosomal recessive (inherited from both parents), or X-linked (the gene is located on the X-chromosome).  “Autosomal” genes always occur in pairs, with one inherited from each parent.  Individuals with an autosomal dominant form of porphyria have one “non-working” gene paired with a “working” (or normal) gene.  Each of their children has a 50% chance of inheriting the non-working gene.  Some of those who inherit the non-working gene will develop symptoms.  Individuals with an autosomal recessive type of porphyria have a pair of non-working genes, and each of their children will inherit one non-working gene for that porphyria which will be paired with the working gene of their partner. Such individuals are referred to as “carriers” and will not have any symptoms.  If two carriers of the same autosomal recessive porphyria have children, each child will have a 25% of inheriting a non-working gene from each carrier parent, and having the disorder.  Because all porphyrias are uncommon, it is very unlikely that more than one type of porphyria will occur in the same family, or that a person with one type of porphyria will go on to develop another type.  However, patients with more than one type of porphyria have been reported.
How are the porphyrias classified?
The best way to classify a case of porphyria is to determine which enzyme is deficient, or not functioning properly.  Normally these enzymes act in a sequence to make heme from simpler molecules.  Heme is a vital substance for all body organs and consists of an iron atom surrounded by a porphyrin molecule. If a specific enzyme is not made properly or there is not enough of the enzyme, it cannot function properly and that step in the heme-making process cannot proceed.
Sometimes other classifications are useful.  Most commonly the porphyrias are divided into the “acute“ and “cutaneous” porphyrias, depending on the primary symptoms.  The acute porphyrias [Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), and ALA-dehydratase Deficiency Porphyria (ALD)] present with sudden attacks of severe stomach pain that last for several days; VP and HCP may also have skin symptoms.  The cutaneous porphyrias present with blistering and scarring of the skin, pain, and/or redness and swelling in sun-exposed areas.  The porphyrias may also be classified as “hepatic” or “erythropoietic”, depending on the organ where the porphyrins accumulate, the liver for the hepatic porphyrias [AIP, HCP, VP, Porphyria Cutanea Tarda (PCT), and Hepatoerythropoietic Porphyria (HEP)] or the bone marrow for the erythropoietic porphyrias [Congenital Erythropoietic Porphyria (CEP), Erythropoietic Protoporphyria (EPP), and X-Linked Protoporphyria (XLP)].
What treatment and prevention are available?
To date, there is no cure for any of the porphyrias. Treatment and prevention depends on the type of porphyria. Preventive measures, which include avoidance of certain drugs and alcohol, as in the hepatic porphyrias, and sun exposure, as in the erythropoietic porphyrias, are also important in those individuals who are identified as having inherited porphyria, even if they have never had symptoms. 
For the acute porphyrias, hospitalization is often necessary for acute attacks. Medications for pain, nausea and vomiting, and close observation are generally required with monitoring of salt and water balance. Harmful drugs should be stopped.  Attacks are treated with either glucose loading or intravenous administration of hemin (Panhematin®).  Attacks can be prevented in many cases by avoiding harmful drugs and adverse dietary practices. 
PCT, both familial and sporadic, can be treated with regularly scheduled phlebotomies (removal of blood) to lower the amount of in the liver or a low dose regimen of hydroxychloroquine as well as removal of factors (for example, certain medications) that activated the disease.
Treatment of the cutaneous porphyrias is dependant on the specific porphyria.  For CEP, blood transfusions to correct anemia, splenectomy (removal of the spleen) are often needed treatments.  Bone marrow transplant (BMT) has also been done in severe cases with good results.  For EPP, treatment with pharmaceutical grade β-carotene (Lumitene, Tishcon) or cysteine may improve sunlight tolerance.  Avoidance of sunlight (and fluorescent lights for CEP) is recommended for all individuals with a cutaneous porphyria as well as those diagnosed with HCP or VP who have porphyria-related sun sensitivity.
Is porphyria progressive or lethal?
Unlike some genetic disorders in which all individuals who inherit a gene mutation become ill,the severity of porphyria varies considerably.  Such variability is due to certain “additional factors” other than the gene itself. Consequently, risks of severe medical difficulties or even death in the acute porphyrias are often diminished when affected individuals are well informed of their diagnosis and adopt suggested precautionary measures.  Even with modern treatment and prevention, some patients still have repeated attacks.  However, progressive deterioration and death from paralysis in the acute porphyrias are very unusual.
Should doctors be informed that an individual has porphyria, even if it is latent?
Yes!  The diagnosis of porphyria is always an important item of medical information, even when there are no symptoms.  It may, for example, influence the choice of drugs to treat other conditions, the choice of anesthesia for surgery, or dietary recommendations.
What diagnostic tests are available? 
There are many laboratory tests available for the porphyrias, and it is often difficult to decide which should be chosen.  Many of these tests are expensive.  The results are often difficult to interpret.  The tests vary in sensitivity and specificity.  If a test is “sensitive”, it is unlikely to be falsely negative (that is, fail to diagnose porphyria in a patient who has the disorder).  If a test is “specific”, it is unlikely to be falsely positive (that is, diagnose porphyria in a patient who does not have the disorder).  Certain tests are both sensitive and specific in patients who have symptoms that are suggestive of a porphyria.  It is advisable to have the testing performed by a laboratory that has expertise in the clinical aspects of porphyria and can provide a valid interpretation of the test results.  If testing has been performed in laboratories other than porphyria laboratories, consultation with a porphyria expert is advised before a final diagnosis is made.
When abdominal and neurological symptoms suggest an acute porphyria, the best screening tests are urinary aminolevulinic acid (ALA) and porphobilinogen (PBG).  When there are cutaneous symptoms that suggest porphyria, the best screening test is a plasma porphyrin assay.  If one of these screening tests is abnormal, more extensive testing, including urinary, fecal, and red blood cell porphyrins, are often indicated.  Urinary, fecal, and red blood cell porphyrin measurements are not very useful for initial screening because they lack either sensitivity or specificity and, therefore, are often difficult to interpret.  Measurement of heme biosynthetic enzymes in red blood cells or lymphocytes is not appropriate for screening unless it is part of a family study that is done after someone in the family is already known to have a specific enzyme deficiency.
DNA testing to identify the specific mutation in an individual’s porphyria-causing gene may be indicated to confirm the diagnosis of a specific porphyria.  Before requesting DNA testing, it is recommended that patients have biochemical testing (urinary, stool and/or plasma porphyrins and porphyrin precursors (ALA and PBG) and/or enzyme assays). However, many patients have not had an acute attack or are not symptomatic at present, so biochemical testing may be inconclusive.
In contrast, DNA testing is the most accurate and reliable method for determining if a person has a specific porphyria and is considered the "gold standard" for the diagnosis of genetic disorders. If a mutation (or change) in the DNA sequence is found in a specific Porphyria-causing gene, the diagnosis of that Porphyria is confirmed. DNA analysis will detect more than 97% of known disease-causing mutations. DNA testing can be performed whether the patient is symptomatic or not. Once a mutation has been identified, DNA analysis can then be performed on other family members to determine if they have inherited that Porphyria, thus allowing identification of individuals who can be counseled about appropriate management in order to avoid or minimize disease complications.
What is “latent” porphyria?  If my doctor told me that I have “latent” porphyria, does this mean that I will never have any symptoms?
Individuals with a disease-causing mutation without symptoms have "latent" porphyria. However, this does not mean that such an individual will never have symptoms. Genetic factors (that is, the presence of a porphyria-causing gene mutation is not the only factor involved. Exposure to certain environmental factors, such as drugs, chemicals, diet, and sun exposure can, depending on the type of porphyria, greatly influence whether an individual with a mutation in a porphyria-causing gene has symptoms and the severity of symptoms. There may also be additional factors, including additional genes, that may modify the symptoms. This is why it is important that all family members of individuals diagnosed with porphyria be tested whether they have symptoms or not, and that all individuals who have a confirmed diagnosis of porphyria be educated about and follow the recommended precautionary and preventive measures for porphyria.
Where can I find a porphyria expert?  What other type of doctor can diagnose me properly and what type of specialist should I see if I have porphyria.  
There are several Porphyria experts in the US and outside the US, including the Porphyria Centers in this Consortium. Information about other experts can be obtained by contacting the American Porphyria Foundation ( or one of the Porphyrias Consortium members.  If a porphyria is suspected, any physician can order the appropriate tests.  Since interpretation of these results may be difficult, it is best for the physician or healthcare professional to consult with a porphyria expert for an accurate interpretation of the results and, if necessary, advice about additional testing, treatment, or prevention and precautionary measures.
Can I have more than one type of porphyria?
Because all porphyrias are uncommon, it is very unlikely that more than one type of porphyria will occur in the same family, or that a person with one type of porphyria will go on to develop another type. However, patients with more than one type of porphyria have been reported.
Can porphyria improve with age?
The symptoms of porphyria do not improve with age, per se.  Untreated, the symptoms and the secondary effects of long-term symptoms will get worsen over time. However, with proper diagnosis, treatment of acute attacks (in the acute porphyrias), and following recommended preventive measures, it is possible that symptoms may be lessened.
Should I be tested often?  How often?
Monitoring of porphyrin levels and other follow-up testing is dependent on the type of porphyria and the medical status of the individual.  It is, therefore, important that a person who has been diagnosed with porphyria be followed by a porphyria expert.
Does porphyria affect my liver?  Should I have liver tests?
Liver function tests should be performed routinely on all individuals diagnosed with porphyria.
Do people have liver transplants for poprhyria?
Liver transplantation may be beneficial for individuals with end-stage liver disease as a result of porphyria. 
My doctor diagnosed me with porphyria but the porphyria expert said I did not have it.  Why would this happen and should I be retested?
Such a situation needs to be dealt with on an individual basis.  Whether further testing is recommended depends on how the patient was initially diagnosed and how the porphyria expert made the decision that porphyria is not the diagnosis.  The results of biochemical testing are sometimes interpreted incorrectly by a physician who is not an expert in porphyria. Review of the results of the biochemical testing by a porphyria expert may determine that the results are not consistent with what is typically seen in a patient with porphyria during an attack. The results of DNA analysis may also contribute to the porphyria expert saying that it is unlikely that the patient has porphyria. DNA analysis, although considered to be the “gold standard” for diagnosis, is not perfect in that the patient may have a mutation in a part of the porphyria gene that is not analyzed by routine testing or the patient has a mutation in a porphyria gene that was not analyzed. In the event that a diagnosis of porphyria is still suspect, then it is recommended that the patient undergo additional biochemical testing at the time of an acute attack.  Additionally, further testing may include DNA analysis for other acute porphyrias (if only one or two were tested). 
Is porphyria research being conducted?  How can I volunteer to participate in research? 
Yes. For additional information about research being conducted and how to volunteer to participate, please contact either the Porphyrias Consortium Coordinator by email ( or telephone (212-659-6779) or one of the site coordinators (see list of Porphyrias Consortium Members for locations and contact information).
Acute Porphyrias
Does surgery or pregnancy pose additional risks?
Porphyria-related risks of surgery and pregnancy depends on the type of porphyria.  Surgery may increase the risk of an attack of the acute porphyrias.  This risk can be greatly reduced if certain precautions are taken, including the type of anesthesia used.  The patient’s surgeon and anesthesiologist should consult a porphyria expert prior to hospitalization for surgery.  Such consultation may also be helpful during pregnancy.  Although attacks of acute porphyria can occur during pregnancy, the risk appears to be less than formally thought.  Treatment of acute attacks during pregnancy is feasible.
What drugs are safe and unsafe?
For information about safe and unsafe drugs in the acute porphyrias, it is best to consult the American Porphyria Foundation Acute Porphyrias Drug Safety Database ( or the European Porphyria Initiative (  The databases contain expert assessments of the potential of drugs to provoke attacks of acute porphyria (AIP, VP, HCP & ADP) based on the available evidence. However this evidence is not always complete, which may lead to some degree of uncertainty.   The information in these databases is meant as guidance to health care professionals. It must be made clear that the prescription of drugs to a patient with acute porphyria is entirely at the risk of the physician in charge.
Since most commonly used drugs have not been tested, they should be avoided if at all possible.  If a question regarding drug safety arises, a physician or medical center specializing in porphyria should be contacted.
Can men have acute porphyria?
Yes.  Since the acute porphyrias are inherited in an autosomal dominant pattern, males and females are equally at risk for having an acute porphyria.  Exposure to certain environmental factors, such as drugs, chemicals, and diet, greatly influence whether an individual—males and females--with a mutation in a porphyria-causing gene has symptoms and the severity of symptoms.  However, one of the environmental is hormones, and, therefore, attacks are more common in women than in men.  Women may experience cyclical acute attacks associated with their menstrual cycle, starting in puberty.  Such attacks in women may occur after ovulation and during the last part of the menstrual cycle when progesterone levels are high.
Do I need a special diet with porphyria?
Nutritional recommendations for the acute porphyrias emphasize a high carbohydrate intake as part of a balanced diet that provides all essential nutrients. The recommendations include an adequate intake of dietary fiber, vitamins and minerals. The goals are to prevent acute attacks of Porphyria that may be related to diet, avoid deficiencies of nutrients, and maintain a normal body weight. More information on diet on theAmerican Porphyria website (
Will porphyria affect my thinking and memory?  
Generally, the acute porphyrias do not affect thinking and memory.  However, a person may experience some neurological effects, including confusion, convulsions, muscle weakness, and, rarely, paralysis, due to effects on the nervous system.
What precipitates a porphyria attack?
In an individual with an acute porphyria, an acute attack can be brought on by certain drugs, hormones in women, environmental factors including chemicals of various types, nutrition including fasting and low carbohydrate diets, alcoholic beverages, medical and physical stress, and physical fatigue.
I have acute porphyria:  Can I do the following:   take a flu shot, donate my organs, take a CAT scan with the contrast? 
Flu shots are not contraindicated for individuals diagnosed with acute porphyria, and can be taken safely. Any immunizations appear to be okay.  In fact, since other illnesses can bring on a porphyria attack, remaining healthy is one of the most important ways to prevent acute attacks.
There has been no information to date to suggest that CAT scans with or without contrast agents should not be performed on an individual with porphyria. 
Organ donation would be up to a particular transplant program or network.  In acute porphyrias any organ should be acceptable except perhaps the liver.  In the case of PCT organ donation would most likely be acceptable in the absence of a history of hepatitis C or HIV. 
What should I do if the drug I need is on the unsafe list?
Drugs on the “unsafe” list are those drugs that should be avoided by individuals diagnosed with an acute porphyria because they have been found to provoke an acute attack in some individuals.  If a drug prescribed for an individual diagnosed with an acute porphyria is on the “unsafe” list, the prescribing physician should check the Drug Database for a safe alternative.  No drug should be withheld if it is judged essential for optimum treatment of a life-threatening condition (e.g. chemotherapy for cancer).  The risk versus the benefit should be assessed and discussed with the patient.  For help with this assessment you may wish to contact a Porphyria expert.  It may be recommended that a patient undergo biochemical monitoring in the early stages of treatment It must also be noted that response to drugs in patients with an acute porphyria is extremely variable and individuals may be encountered who have used an unsafe drug without adverse effect.
Cutaneous Porphyrias
Is sunlight always harmful?
Sun sensitivity can occur in all but two types of porphyria, specifically AIP and ADP.  The degree of sensitivity to sunlight varies considerably.  Patients with sun sensitivity have high levels of porphyrins in the blood plasma which, depending on the type of porphyria, have originated from the liver or the bone marrow.  Ultraviolet light interacts with porphyrins in such a way as to damage skin tissue.  Some treatments may help patients tolerate sun exposure even without lowering porphyrin levels.  In some cases, treatment can lower porphyrin levels and sunlight can be tolerated.
Should I use a special sunscreen?  
Most patients with a cutaneous type of porphyria must learn to avoid sunlight as much as possible.  Protective clothing may also be recommended.  For patients with EPP, treatment with pharmaceutical grade β-carotene (Lumitene, Tishcon) or cysteine may improve sunlight tolerance but does not lower porphyrin levels.  Over-the-counter sunscreens and over-the-counter beta carotene (vitamin A) is not effective.

                               "Remember....Research is the key to your cure!"

Wednesday, October 14, 2015

57th American Hematology Society Meeting

57th American Hematology Society Meeting

The APF will be exhibiting at the 57th American Hematology Society meeting in Orlando , Fl. The convention is held from December 5 to 8. We would like to ask you to help us man the exhibit booth.
We hand out physician education materials at the convention for the 8000 attendees.  Since many of you visit with hematologists, and since hematologists treat and diagnose many patients, we attend the ASH meeting each year as a part of our physician education program.
As the premier event in malignant and non-malignant hematology, this meeting will provide attendees with an invaluable educational experience and the opportunity to:
Review more than 3,000 scientific abstracts highlighting the updates in the hottest topics in hematology
Interact with the global community of more than 20,000 hematology professionals from every sub-specialty
Attend the hallmark Education and Scientific Program sessions
Network with top minds in the field
Please volunteer to help man the booth.  For details, contact us at 866.APF.3635.

"Remember....Research is the key to your cure!"

Friday, October 9, 2015

Genetics 101 of Porphyria

Genetics 101:  Basic genetics and inheritance

In order to better understand the Porphyrias and how the disorders are inherited, it is helpful to understand some concepts of basic genetics and inheritance patterns.

DNA, Chromosomes, and Genes:

Deoxyribonucleic acid (DNA) is a nucleic acid that contains the instructions used in the development and functioning of all known living organisms and some viruses. DNA is often compared to a set of blueprints or a recipe or a code because it contains the instructions needed to make certain proteins, which are the complex molecules that do most of the work in our bodies. Each of these proteins has a specific function in the cell, and, ultimately in how the organism develops, its physical makeup, and how it functions day-to-day. The DNA segments that carry this genetic information are called genes. The size of each gene varies greatly, and there are about 20,000 genes that are distributed along the 23 pairs of chromosomes.
A DNA molecule is a twisted double-strand of building blocks, called nucleotides.  It is like a twisted ladder, with the vertical stringers made of phosphates and sugars and the rungs made of pairs of nucleotides. There are four nucleotides in DNA:  adenine (A), thymine (T), guanine (G), and cytosine (C). Also important is that on each rung of this ladder, A always pairs with T, and G always pairs with C. These nucleotides along the ladder are like letters in a word, and put together in their specific order make up the words in a detailed set of instructions. These instructions are read using a special code, called the genetic code.
GenGenome Management Information System,
Oak Ridge National Laboratory
DNA is a double helix formed by base pairs attached to a sugar-phosphate backbone.
Within cells, DNA is organized into long structures called chromosomes. A chromosome is like a cookbook with many recipes (or genes) that tell the body how to function. The human body is made up of trillions of cells and over 200 different cell types like various blood, liver, and brain cell types.  Each cell contains 46 chromosomes. Each chromosome can be identified by its relative size and location of the centromere, a constriction in the chromosome. 
The chromosomes come in pairs.  Since there are 46 chromosomes, there are 23 pairs of chromosomes.  One chromosome in each pair comes from the person’s father.  The other chromosome in each pair comes from the mother.
The first 22 pairs of chromosomes are called “autosomes”.  The autosomes are numbered 1-22.  These chromosomes determine an indivdual’s physical appearance and tell the body how to function day-to-day. 
The 23rd pair of chromosomes is called the “sex chromosomes”.  Parts of these chromosomes determine whether an individual will be male or female, but they also carry additional important information.  A female has two X chromosomes.  A male has one X chromosome and one Y chromosome.
Along each chromosome, there are thousands of genes. Since the chromosomes come in pairs, the genes along them also come in pairs. This means that the genes that are found on one chromosome in each pair are the same as the genes that are found on the other chromosome in that pair. The sex chromosomes are an exception.  Most of the genes that are located on the X chromosome are different from the genes that are located on the Y chromosome. For example, the ALAS2 gene, involved in X-linked Erythropoietic Protoporphyria (EPP), is on the X chromosome, but is NOT on the Y chromosome.
Each gene is a set of instructions that tells the cell how to make a specific product called a protein. These proteins have the job of telling the body how to grow and develop as well as how to do all the things that are necessary for the body to work properly every day.  Any change in one of these genes may interfere with the body’s ability to make one of these necessary proteins. A gene change is called a mutation.
Autosomal Dominant Inheritance:
Since autosomal genes always occur in pairs, with one coming from each parent, individuals with an autosomal dominant form of porphyria [Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), Variegate Porphyria (VP), familial Porphyria Cutanea Tarda (f-PCT)] have one non-working gene with a mutation on one chromosome, paired with a working (or normal) gene on the other chromosome.  Usually, the non-working gene was inherited from one of the individual’s parents. Rarely, a new mutation (also called a “de novo” mutation) can occur in the affected individual and not be present in one of his parents. However, the de novo mutation will be inherited by 50% of the patient’s offspring. In individuals with an autosomal dominant form of porphyria, there is a 50% chance with each pregnancy that the non-working gene will be passed on to a child.  Some of those who inherit the non-working gene will develop symptoms.

Autosomal Recessive Inheritance:

Individuals with an autosomal recessive type of porphyria [Congenital Erythropoietic Porphyria (CEP), Erythropoietic Protoporphyria (EEP) and Hepatoerythropoietic Porphyria (HEP)] have a pair of genes with mutations that affects the function of the enzyme encoded by the gene. In such individuals, one mutant gene was passed on from each of their parents. If their children only inherit one mutant gene for that porphyria, which will be paired with a normal gene from the other parent, and the child will be a “carrier”, but will not have symptoms.
If two carriers of the same or similar mutant recessive gene have children, there is a 25% chance with each pregnancy that the child will inherit two mutant genes (one from each carrier parent), and these children will develop symptoms of the disease.
X-Linked Inheritance:
The “sex chromosomes” are the X-chromosome and the Y-chromosome. Females have two X-chromosomes, and males have one X-chromosome and one Y-chromosome. In X-linked disorders [for example, X-Linked Protoporphyria (XLP], the gene is located on the X-chromosome, and the risk for children depends on the gender of the affected parent. If a female has the mutation, there is a 50% risk for passing the mutation onto her children with each pregnancy.
© 1995 Greenwood Genetics Center
For a male who has the gene mutation, all of his daughters will get the mutation, but none of his sons.
© 1995 Greenwood Genetics Center
X-linked inheritance (when the mother has the mutation)
If a daughter gets the gene mutation from either her mother or her father, the daughter may or may not have symptoms, and the severity of symptoms may vary even among the females in the same family. For this reason, in most X-linked disorders, including X-Linked Protoporphyria, females who have the gene mutation are referred to as “heterozygous” for the mutation, rather than “carriers” which infers that they will not have any symptoms (as in autosomal recessive disorders). If a son gets the mother’s mutation, he will have symptoms.

Thursday, October 8, 2015

Clinuvel and FDA discuss EPP indication and regulatory pathways for SCENESSE®

Clinuvel and FDA discuss EPP indication and regulatory pathways for SCENESSE®

The attached document discusses the latest news from FDA and Clinuvel:
Type C meeting provides guidance for follow up and further discussions between FDA and Clinuvel.
Clinuvel Pharmaceuticals Limited (ASX: CUV; ADR:CLVLY; XETRA:DAX) today announced that on September 30 it met in Silver Spring, USA, with the US Food and Drug Administration's (FDA's) Division for Dermatology and Dental Products (DDDP) and representatives of the Center of Drug Evaluation and Research (CDER). The objective of the meeting was to discuss the US regulatory review of SCENESSE® (afamelanotide 16mg) to be made available to American erythropoietic protoporphyria (EPP) patients. In 2014 SCENESSE® was granted marketing authorisation by the European Medicines Agency as a prophylactic photoprotective drug for adult EPP patients.
The DDDP stated that it was seeking a regulatory pathway to make SCENESSE® available in the US, and the regulatory avenue of Accelerated Approval was suggested, pending FDA's review, analyses and further discussions on available photoprovocation and data on quality of life in EPP patients.
A discussion was held on the drug's benefits to patients who had received SCENESSE®. Expert European and US porphyria clinicians were invited to share their experience in the treatment of EPP patients and the use of SCENESSE® in their patients. Further discussions will be held with the DDDP following the review of photoprovocation and quality of life data.

"Remember....Research is the key to your cure!"

Wednesday, October 7, 2015

CME Course share with your Medical community today

New Continuing Medical Education Course CME

Exciting New Continuing Medical Education Course CME With Drs Herbert Bonkovsky, Lisa Kehrberg and Brendan McGuire. 
Medscape has produced an outstanding new physician education video that can be found on the Medscape website.

Acute Intermittent Porphyria: A View From the Trenches:
Herbert Bonkovsky, MD;  Brendan M. McGuire, MD, MS;  Lisa Kehrberg, MD
CME/CE Released: 09/25/2014; Valid for credit through 09/25/2015
Please advise your physicians of this free CME course for CME credit.
You, too, can watch the video by joining the complimentary Medscape online site.  
You can register easily and view this and other porphyria videos, as well as a host of additional excellent articles written about all types of porphyria.  

Our thanks to Dr Bonkovsky, Dr Kehrberg and Dr McGuire.  

Monday, October 5, 2015

AIP Research Experiences

Will you help with medical research?

                                                        Why is important?  

What does it entail? 

                                                                                       When does this research happen?

                              What Happens?

                   Take a look at a few who have expressed why research is so important!

Tracy Yelen ~ Research Experience

Type of Porphyria: 
Acute Intermittent Porphyria (AIP)
"If you're at all interested in what they are doing to me in this Panhematin trial, I am happy to share. During the entire stay, the medical team accessed my port.  They drew all the blood they wanted without all the usual IV sticks, which is nice. Every morning after breakfast we did the infusions, which may or may not be a placebo.  Neither the nurses nor I were allowed to see what was pumping into me.  So I am blindfolded and there are sheets hung in the room to cover the medicine and tinfoil around the lines. It takes only a couple hours to complete.  I snoozed and chatted with the sweet nurse.  Outside of that, the dextrose fluids are flowing in through my port 24/7. Otherwise, it was pretty uneventful.  Why do I tell you this?  Basically, I want to remind you of how important it is to volunteer as a research patient if you ever get the opportunity. There are lots of trials that even perfectly well people can do for various different studies and various different medical reasons."
~Tracy Yelen, AIP

Steve Stevens ~ Research Experience

Type of Porphyria: 
Acute Intermittent Porphyria (AIP)

"I volunteered for the Alnylam Study about a month ago and yesterday (March 30) I went to Birmingham, Alabama to do the initial Observation Part of it. The APF set up everything to get me there and back home. Jessica handled all the travel arrangements and I can't say enough of the awesome job she did. I didn't have any layovers longer than 45 minutes. That was amazing because I have had layovers in the past last for hours. Thank You Jessica for the great itinerary and asking for any input before you booked the flight. Before I forget, the plane tickets, food, taxi costs, etc. was covered by the APF. It didn't cost me a penny. I got to meet Dr. Bloomer and Dr. Singal. They explained to me what the Study was and answered all my questions. I haven't met many doctors like them, after talking to them I could see and feel their sincerity about helping us. They are great. The Study Administrator's name is Toni and she is so fantastic. She sat with me and explained the paperwork in detail and answered any questions I had pertaining to the Study or questionnaires that I was answering. I was very impressed how professional and organized she is. She made sure everything was completed and I had enough time to get back to the airport in time for my trip home. She and the doctors are very special people. I cannot say enough about them.
I am glad I volunteered for the Study and would encourage anyone that has one of the acute porphyria's to do so also. I hope to volunteer for future research and hope others do too. You are helping yourself, your family and your future generations."
~ Steve Stevens, AIP

                          "Remember....Research is the key to your cure!"

Friday, October 2, 2015

Your APF Membership

Your APF Membership
We are currently working on the next issue of the Newsletter, where you can find latest news, updates and stories from the porphyria world.Our members, who made deductible charitable contributions, will receive the fresh issue.
The APF is able to maintain our physician and patient education programs and many other services because of your support. Since we do not receive government funding, we need your support and donations. Is your membership and contact information up to date? If you have moved, please update us with your current address. Be sure to send us your email address so you can receive the E-news.

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"Remember....Research is the key to your cure!"

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