Wednesday, July 19, 2017

Porfiria

Porfiria

Introducción

Las porfirias son un grupo de trastornos genéticos causados por problemas con la forma en que el cuerpo produce una sustancia llamada hemo. El hemo se encuentra en todo el cuerpo, especialmente en la sangre y en la médula ósea, donde transporta oxígeno.
Existen dos tipos principales de porfirias: Uno es el que afecta la piel (cutáneo) y el otro es el que afecta el sistema nervioso. Las personas que tienen porfiria cutánea desarrollan ampollas, picazón e inflamación en la piel cuando se exponen al sol. El tipo de porfiria que afecta al sistema nervioso se llama porfiria aguda. Los síntomas incluyen dolor en el pecho, abdomen, brazos o piernas, espalda, adormecimiento de los músculos, hormigueo, parálisis o calambres, vómitos, estreñimiento y cambios mentales o en la personalidad. Estos síntomas pueden aparecer y desaparecer.
Algunos desencadenantes pueden causar una crisis, como ciertas medicinas, el cigarrillo, el consumo de alcohol, las infecciones, el estrés y la exposición al sol. Las crisis se desarrollan en horas o días. Pueden durar días o semanas.
La porfiria puede ser difícil de diagnosticar. Requiere de exámenes de sangre, orina y heces. Cada tipo tiene un tratamiento diferente. Parte de este es evitar los desencadenantes. También puede incluir tratamiento con hemo (hematina) a través de una vena, medicamentos para aliviar los síntomas o extracción de sangre para reducir la cantidad de hierro en el cuerpo. Las personas que presentan varios episodios quizás deban ser internadas.
NIH: Instituto Nacional de la Diabetes y las Enfermedades Digestivas y Renales

https://medlineplus.gov/spanish/porphyria.html

Monday, July 17, 2017

What are common signs and symptoms of AHP?

What are common signs and symptoms of AIP?

Severe abdominal pain: the most common AIP symptom

The most common symptom of AIP is severe abdominal pain that usually cannot be relieved with pain medicine such as Advil® (ibuprofen) or Tylenol® (acetaminophen). More than 85% of people who develop AIP symptoms have abdominal pain.

Experiencing symptoms is known as having an “AIP attack.” Symptoms may occur for a set period of time, then go away – only to come back later.

Common AIP symptoms

Symptoms can occur in many different areas of your body during an AIP attack. These include:

GASTROINTESTINAL (GI) SYMPTOMS

  • Abdominal pain
  • Vomiting
  • Constipation
  • Diarrhea
  • GASTROINTESTINAL (GI)
  • URINARY SYSTEM
  • BRAIN OR NERVOUS SYSTEM
  • HEART OR BLOOD VESSELS

Early diagnosis and treatment of AIP are critical

AIP attacks can be very serious. And symptoms may get worse over time. Untreated attacks can cause serious damage to your nervous system —including paralysis, and even death. That's why early diagnosis and treatment of AIP is so important.
If you have any of the symptoms listed above, talk to your doctor right away.

What triggers AIP attacks?

  1. Steroid hormones, particularly estrogen and progesterone. These hormones fluctuate the most during the 2 weeks before a woman’s menstrual periods start.
  2. Unhealthy behaviors such as drinking alcohol, smoking, or using illegal drugs.
  3. Stress on the body caused by infections, surgery, or physical exhaustion.
  1. Certain prescription drugs. Attacks can also be triggered by starting a new prescription drug.
  2. Changes in eating patterns such as fasting or crash dieting.
  3. Mental stress or emotional exhaustion.
IF YOU HAVE ATTACKS OF SEVERE ABDOMINAL PAIN OR OTHER SYMPTOMS THAT SEEM TO BE TRIGGERED BY ANY OF THE FACTORS ABOVE, TALK TO YOUR DOCTOR RIGHT AWAY.

What causes AIP?

AIP is caused by a partial lack of an enzyme known as porphobilinogen deaminase (PBGD). An enzyme is a type of protein that helps to regulate the bodys tissues and organs. Enzymes carry out almost all of the thousands of chemical reactions that take place in cells.
If you have AIP, you have about half of the normal amount of PBGD in your body. This is usually enough for your body to do what it is supposed to do. But triggers like those listed above can upset your body's chemical balance enough to cause symptoms.

Learn about a treatment for repeated acute AIP attacks

QUESTIONS FOR YOUR DOCTORDOWNLOAD OUR HELPFUL CHECKLISTABOUT PANHEMATINLEARN HOW PANHEMATIN TREATS AIP

TAKE STEPS TO HELP MANAGE YOUR AIP:

  • Try to identify your possible triggers. Then try to reduce or avoid as many as you can. If you continue to experience attacks, keep writing down suspected triggers. Look for patterns of things that occurred right before an attack to identify any changes you can make. Talk to your doctor if you need help.
  • Be careful when changing your eating patterns. If you want to lose weight, get advice from your doctor or nutritionist before starting any diet.
  • Call your doctor at the first sign of an attack. Repeat attacks are often similar. They may start the same way and you may have the same symptoms.
  • Wear a medical alert bracelet. Doctors need to know about your AIP so that they do not prescribe drugs that may make your AIP worse.

Wednesday, July 12, 2017

Updates on PCT Porphyria

Porphyria cutanea tarda

Created 1997.

What is porphyria cutanea tarda?

Porphyria cutanea tarda (PCT) is the most common type of porphyria.
An increase in porphyrins in the skin result in photosensitivity, ie, the skin is damaged by light.

What are the symptoms of porphyria cutanea tarda?

Individuals with PCT present with increasingly fragile skin on the back of the hands and the forearms. Features include:
  • Sores (erosions) following relatively minor injuries
  • Fluid filled blisters (vesicles and bullae)
  • Tiny cysts (milia) arising as the blisters heal
  • Increased sensitivity to the sun
Although these features may also occur on the face and neck as well, it is more common to notice mottled brown patches around the eyes and increased facial hair (hypertrichosis). Occasionally the skin becomes hardened (scleroderma) on the neck, face or chest. There may be small areas of permanent baldness (alopecia) or ulcers.
Characteristically, the urine is darker than usual, with a reddish or tea-coloured hue.
The clinical appearance of variegate porphyria is similar but the biochemical abnormality is different.








What is the cause of porphyria cutanea tarda?

PCT is due to a defective enzyme in the liver (uroporphyrinogen decarboxylase). This is involved in synthesis of the red pigment in blood cells (haem). Some families carry an enzyme that is prone to oxidation under certain circumstances, most often due to iron accumulation.
There are basically two forms of PCT, type 1 and type 2.
Type 1 PCT generally begins in mid-adult life after exposure to certain chemicals that increase the production of porphyrins (precursors of haem) in the liver. These include:
  • alcohol (in 50% patients)
  • oestrogen eg oral contraceptive, hormone replacement (in 50% of affected women) or liver disease
  • polychlorinated aromatic hydrocarbons (eg, dioxins, when PCT is associated with chloracne).
  • iron overload, due to excessive intake (orally or by blood transfusion), viral infections (hepatitis, especially hepatitis C, in 15%) or chronic blood disorders such as thalassaemia (acquired haemochromatosis), or hereditary haemochromatosis (in 20%)
Type 2 PCT is familial and associated with abnormal genetic variants of uroporphyrinogen decarboxylase. Trigger factors are less often involved and onset of PCT is often younger than in type 1 PCT.

What investigations should be done?

  • Skin biopsy : characteristic changes are seen which differentiates PCT from other blistering diseases.
  • Examination of the urine with a Wood's lamp: may reveal coral pink fluorescence due to excessive porphyrins.
  • 24 hour urine porphyrin profile: total porphryins are usually elevated 5- to 20-fold above the upper reference limit. Most of the excreted porphyrins are uroporphyrin and a 7-carboxyl porphyrin.
Other important tests include:
  • Complete blood count to assess haemoglobin levels.
  • Measurement of iron stores, which may be increased in over 30% of patients.
  • Liver enzymes because the liver sometimes does not function normally.
  • Fasting blood sugar because of the increased incidence of diabetes.
  • Antinuclear antibodies because of the increased incidence of lupus erythematosus.
  • Viral hepatitis studies
If a blood ferritin shows iron stores are increased, further investigations may include transferrin saturation and genotyping for hereditary haemochromatosis.

What is the management of porphyria cutanea tarda

  • Avoid alcohol, oestrogen, and iron.
  • If using pesticides, be very careful to avoid contact with polychlorinated aromatic hydrocarbons (eg. 2,4,5T).
  • Apply an opaque sun-block and cover up when outside; the responsible light is the "Soret" band at 400 nm which is unfortunately not blocked by most sunscreens.
  • Use tanning cream containing dihydroxyacetone: this can block the responsible light to some extent.
  • Phlebotomy (removal of blood) — up to 500 ml blood is removed every one to two weeks until the haemoglobin and iron levels drop to low normal levels. It may take 3 to 6 months to improve. Venesection may need to be repeated after a year or more.
  • Antimalarial tablets, ie, low-dose chloroquine or hydroxychloroquine may be recommended, but must be used cautiously. This medication makes the porphyrins more soluble so more are excreted in the urine.
  • Autologous red cell transfusion (this is a blood transfusion using the patient's own red cells that have been washed to remove plasma thereby reducing the circulating porphyrins).

 

  1. Deferasirox for Porphyria Cutanea Tarda
    Graeme M. Lipper, MD, Medscape, 2012
  2. A porphomethene inhibitor of uroporphyrinogen decarboxylase causes porphyria cutanea tarda.
    John D Phillips et al., Proc Natl Acad Sci U S A, 2007
  3. Porphyria variegata and porphyria cutanea tarda in siblings: chemical and genetic aspects.
    C J Watson et al., Proc Natl Acad Sci U S A, 1975
  4. Alcohol and Skin Disorders: With a Focus on Psoriasis
    Natalia Kazakevich et al., Medscape, 2011
  5. Fingernail and Toenail Abnormalities: Nail the Diagnosis
    Mark P. Brady, PA-C, Medscape, 2015

Monday, July 3, 2017

Michael Boone AIP Research Experience

Michael Boone ~ Research Experience
Type of Porphyria: 
Acute Intermittent Porphyria (AIP)
In late 2008, after a yearlong battle, I was diagnosed with acute intermittent porphyria (AIP).  At first, I was relieved to finally have answers. Then, I learned how little there was that could be done with the disorder.  I wasn't the first in my family to be diagnosed.  In the late 1950's my great uncle was diagnosed and then died of the disorder.  My grandmother would follow in the early 60's at the young age of 28.  My mother was also diagnosed in the mid 1990's.  Needless to say I thought I understood the seriousness of the situation, but after learning what my treatment options were, I became nervous.  After all, I'm married and have two children. How was my ability to support them going to be affected?  I did some research on the disorder and stumbled across the American Porphyria Foundation.  Through conversing with them I learned of some opportunities to help find better treatments and, maybe, a cure.  I jumped at the chance with more concern about my children having the gene than with concern about myself.
The first study I enrolled in was simple and straight forward.  It required no travel and only one time did I have to send them any samples.  It was simply blood which was drawn at my local doctor’s office and then mailed off to Salt Lake City.  The Longitudinal Study is a simple study and I strongly encourage everyone to take part in this study.  It was through this study that I was able to get gene testing done at no cost to me.  Now, I have concrete proof of my diagnosis.  I am still in the study and once in a great while fill out more papers with questions about how I am doing.  Like I said-- simple and straight forward.

The second study I took part in was the Panhematin study.  This study required me to fly to Galveston, Texas and stay there in the hospital for four days.  The research grant paid for all of my travel expenses and there was of course no in hospital expenses for me to worry about.  The APF arranged all the travel. Again, this study had a simple procedure.  Once I began feeling as though I had an attack coming on I contacted the foundation and they made the travel arrangements.  The next day I flew into Houston Hobby Airport where a car service picked me up and drove me to University of Texas Medical Branch in Galveston.  This particular study was a double blind study.  That means that neither I, nor the doctors and nurses know if I was getting the Panhematin or a placebo.  Only the pharmacist knew.  In order to keep the secrecy I had to wear a blindfold, the tubing and medicine was wrapped in foil, and a sheet was also placed between me and the bottle of whatever I was getting.  This happened once a day for four days, and I was also on normal saline with 10% dextrose constantly while I was there.  In all my experience with this study was good.  Things went smoothly and before I knew it, I was on my way back home to Colorado.

Thursday, June 29, 2017

Data Presented at ICPP Show Encouraging Results for Givosiran in AHP Patients

Data Presented at ICPP Show Encouraging Results for Givosiran in AHP Patients
Mathew Shanley
Published Online: Monday, Jun 26, 2017
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At the 2017 International Congress on Porphyrins and Porphyrias (ICPP) this week in Bordeaux, France, Alnylam Pharmaceuticals is presenting new data on Givosiran (ALN-AS1) for the treatment of acute hepatic porphyrias (AHP).

In a randomized, double-blind, placebo-controlled study, Givosiran demonstrates a decreased annualized attack rate and hemin usage. Initial results from an ongoing open-label extension (OLE) study show consistent reductions in porphyria attacks with continued Givosiran treatment.

Hepatic porphyrias are a subgroup of of porphyrias in which the enzyme deficiency occurs in the liver. Acute hepatic porphyrias encompass four diseases: acute intermittent porphyria (AIP) (most common), variagate porphyria, hereditary coproporphyria, and hereditary deficit of delta-aminolevulinic acid dehydratase (most rare).

Currently, urgent treatment with an injection of human hemin and/or perfusion of carbohydrates is required when an acute attack is confirmed. Management of the disorder includes avoiding causal factors to prevent attacks and protect the skin from the light in cases of cutaneous manifestations.

Alnylam’s hope in developing Givosiran, a subcutaneously administered, investigational RNAi therapeutic, is for it to become a novel treatment approach for the prevention of recurrent attacks by targeting ALAS1 for the treatment of AHP, including AIP.

"We believe that a long acting therapeutic agent that has the potential to prevent porphyria attacks and that can be administered via a once monthly, low volume, subcutaneous injection could be a potentially transformative treatment option for patients suffering with this debilitating and potentially life-threatening disease," said Jeff Miller, General Manager of the givosiran program.

"Based on these encouraging interim results and with both Breakthrough Therapy and PRIME designations granted, we will continue to work with global regulatory authorities to rapidly advance givosiran toward regulatory filings and, if approved, to patients. To that end, we remain on track to initiate the givosiran Phase 3 program in late 2017."

Per a press release, the continuing part of the Phase 1 study of the drug is being managed as a randomized, double-blind, placebo-controlled study in up to 24 AIP patients who experience recurrent porphyria attacks. Patients are followed in a 3-month run-in phase, where the amount and frequency of attacks and levels of porphobilinogen (PBG) and aminolevulinate (ALA) are measured prospectively.

Patients who experience at least 1 porphyria attack during the run-in phase are then eligible to enter the study’s 6-month treatment phase, where they are randomized to receive 2 once-quarterly doses or 4 once-monthly doses of placebo or givosiran at 2.5 or 5.0 mg/kg. During the treatment phase, the effects of placebo or givosiran on the number and frequency of porphyria attacks, as well as on the levels of ALA and PBG, are measured prospectively in a blinded manner and then compared to run-in phase results.

Additional measures include safety, tolerability, hospitalizations, use of hemin (FDA approved), levels of ALAS1 mRNA, and givosiran pharmacokinetics. Following the treatment phase, all patients are eligible to receive givosiran in an open-label extension study.

Givosiran has already been granted Orphan Drug Designations in both the E.U. and the U.S. for the treatment of acute hepatic porphyrias. Givosiran also received Breakthrough Designation by the U.S. Food and Drug Administration (FDA), and has been granted PRIME designation by the European Medicines Agency (EMA).

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Porfiria

Porfiria Introducción Las porfirias son un grupo de trastornos genéticos causados por problemas con la forma en que el cuer...