Review of a case of porphyria – pro

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XXyear-old ### with a diagnosis of porphyria. In the year xxxx, xx had multiple admissions. Please identify the treatments ordered and identify possible appropriate treatment options which could mitigate the current frequency of acute care admissions. Patient is on ####.

1.Explain the nature of this patient’s condition, including prognosis.
Acute intermittent porphyria is a rare genetic condition. Its inheritance is autosomal dominant. The deficient enzyme is porphobilinogen deaminase (PBGD), also known as hydroxymethylbilane synthase. This enzyme was formerly known as uroporphyrinogen I-synthase, and this term is still used by some clinical laboratories. A deficiency of PBGD is not sufficient by itself to produce AIP, and other activating factors must also be present. Most people who inherit the gene for AIP never develop symptoms. AIP manifests after puberty, especially in women (due to hormonal influences). Symptoms usually occur as attacks that develop over several hours or days. Abdominal pain, which can be severe, is the most common symptom. Others may include: nausea, vomiting, constipation,
pain in the back, arms and legs, muscle weakness (due to effects on nerves supplying the muscles), urinary retention, palpitation (due to a rapid heart rate and often accompanied by increased blood pressure), confusion, hallucinations and seizures. I must note that sometimes these complaints can overlap with the symptoms of opioid intoxication; this patient is on a high narcotic dose for treatment of porphyria related pain. Sometimes the level of salt (sodium and chloride) in the blood decreases markedly and contributes to some of these symptoms. The skin is not affected.
Precipitating factors include use of hormones, drugs and dietary changes. Known precipitants are alcohol, infection, starvation, and hormonal changes; attacks are more common in women. Only about 10 to 20% of AIP gene carriers become symptomatic during their lifetime. Sometimes, activating factors cannot be identified. The patient’s lifestyle and occupation is highly relvant to the frequency of the attacks; the record notes that some attacks were precipitated by dehydration while working on the sun.
The prognosis is usually good if the disease is recognized and if treatment and preventive measures are begun before severe nerve damage has occurred. Although symptoms usually resolve after an attack, some patients develop chronic pain. Nerve damage and associated muscle weakness can improve over a period of months or longer after a severe attack. Mental symptoms may occur during attacks, but are usually not chronic.

2.Are the frequency of acute admissions typical for this patient’s form of porphyria?
It is unusual. The majority of the patients with this disease can avoid hospitalization with strict attention to diet and avoidance of dehydration and precipitating factors. Most patiensn are never hospitalized after the intial event but some require several hospitalizations annually. The rate of hsopitalizations in this case may be due to a particualrly severe variant of the disease, lack of compliance with recommendations or secondary gain from hospitlaizations.

3.Are there other provider treatments that can result ina decrease of acute care admissions?
AIP patients prone to attacks should eat a normal or high carbohydrate diet and should not greatly restrict their intakes of carbohydrate and calories, even for short periods of time. If weight loss is desired, it is advisable to consult a physician who may then request that a dietitian estimate an individual’s normal caloric intake, which varies greatly from one person to another. Then it may be appropriate to prescribe a diet that is approximately 10% below the normal level of calories for the patient. This should result in a gradual weight loss and usually will not cause an attack of porphyria.
Sulfonulureas can provoke attacks. He has taken azythromycin and levaquin and these should be looked at in relation to attacks, as well as his anti-nausea meds.
Attention to preventive use of Hematin is warranted. Panhematin®, from Ovation Pharmaceuticals, Inc., is the only commercially available heme therapy for treatment and prevention of acute porphyric attacks in the United States. Heme arginate, which is marketed in some other countries, is another preparation of heme for intravenous administration. It is however, not presently available in the United States. Heme therapy is seldom indicated unless the diagnosis of acute porphyria is proven by a marked increase in urine PBG. How heme therapy should be used to prevent attacks is not well established.

4.Are there any other treatments that you would recommend for better inpatient or outpatient management of this condition?
One may consider self administration of heme at first signs of attack. A disease management approach may be helpful. Full assessment by psychaitry may help define factors that provoke attacks and that can be controlled. Retraining for an occupation that avoids dehydration may be considered.

5.Are there any self care treatments that the patient can self administer that could resutl in adecrease ina cute care admission?
Yes, several may help
1.Adherence to a high carbohydrate diet
2.Avoidance of precipitating factors
3.Consider home Dextrose or hydration IV or Heme therapy by self infusion to abort incipient attacks.
5.Counselling to manage some of the psychiatric sequellae of the disease and to promote compliance
6.The issue of addiction needs to be adresses. Chronic pain often requires narcoitcs but a PCA or intrathecal system may allow lower levels of narcotics and might provide patient controlled analgesia sufficient to avoid some hospital visits.

6.Re the frequent inpatient admissions necessary or can they be managed at a lower level of care?
A disease management approach can probably decrease the rate of admission but it is very labor intensive and requires expertise that may not be locally available.

7.Are there centers of Excellence for this condition?
The patient lives in ……… The closest expert to my knowledge is Dr. Karl Anderson, Associate Director of the General Clinical Research Center (GCRC) of the University of Texas Medical Branch (UTMB) in Galveston, Texas. Other physicians whom I know or whose work I recognize are Dr. James P. Kushner at
University of Utah and Dr. Desnick at Mount Sinai in NYC. Dr. Anderson used to be and may still be available for telemedical consultations at (409) 772-4661, funded by the Porphyria Foundation.

Because the disease is rare, there are no Centers of Excellence.

8.Is the local hospital sufficient to manage this patient’s symptoms?
Probably, at the point that he is hospitalized 17 times annually, not.

9.Based on the information available, do you concur with the patient’s diagnosis?
The diagnostic workup was not provided for review; however, the clinical picure is consistent with the diagnosis.

10.Based on the information available, should any other tests be performed to rule otuother diagnoses?
Because this disease is rare and can mimic a host of other more common conditions, its presence is often not suspected. On the other hand, the diagnosis of AIP and other types of porphyria is sometimes made incorrectly in patients who do not have porphyria at all, particularly if laboratory tests are improperly done or misinterpreted. The finding of increased levels of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) in urine establishes that one of the acute porphyrias is present. If PBGD is deficient in normal red blood cells then the diagnosis of AIP is established. However, measuring PBGD in red blood cells should not be relied upon by itself to exclude AIP in a sick patient, because the enzyme is not deficient in red blood cells of all AIP patients.

If it is known that someone in a family has AIP and their enzyme value is low in red blood cells, other family Sponsors who have inherited a deficiency of PBGD can be identified by measuring the enzyme in their red blood cells. Latent cases so identified can avoid agents known to cause attacks. However, in some AIP families, PBGD is normal in red blood cells and is deficient only in the liver and other tissues. Falsely low values sometimes occur due to problems with collecting and transporting the sample.

DNA is the material in cells that encodes all the genetic information of an individual. Many different mutations have been identified in the portion of DNA that comprises the gene for PBGD. Almost every family with AIP has a different mutation in this gene. Within one family, however, everyone who inherits a deficiency of PBGD has the same mutation. It is advantageous to know the precise mutation in a family, because that knowledge enables the identification of AIP gene carriers by DNA testing. This approach is much more precise than measuring PBGD enzyme activity in red blood cells. At present, DNA testing for AIP and other porphyrias is available only through a few research laboratories.

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