On-line version ISSN 1657-9534
Colomb. Med. vol.42 no.1 Cali Jan./Mar. 2011
Porphyria and pregnancy. Case report
Noemí Martínez, MD1, Aníbal Nieto, MD, PhD2, María Guzmán, MD1, Soraya Heron, MD1, Álvaro Zapico, MD, PhD3
1. Resident Third Year of Obstetrics and Gynecology, Hospital Universitario Príncipe de Asturias, Universidad de Alcalá, Madrid, España. e-mail: firstname.lastname@example.org, email@example.com, firstname.lastname@example.org
2. Full Professor of Obstetrics and Gynecology. ViceDean of School of Medicine, Hospital Universitario Príncipe de Asturias, Universidad de Alcalá, Madrid, España. e-mail: email@example.com
3. Head of the Service of Obstetrics and Gynecology. Associate Professor, Hospital Universitario Príncipe de Asturias, Universidad de Alcalá, Madrid, España. e-mail: firstname.lastname@example.org
Received for publication February 23, 2010 Accepted for publication September 14, 2010
The porphyrias are a group of diseases caused by a deficiency of enzymes responsible for the synthesis of heme, that can lead to severe disease that requires early diagnosis to avoid complications. The frequency of the disease is low and its association with pregnancy unusual, but it is a good time for patients carrying develop the disease or suffer an exacerbation of the same, hence the vital importance of prophylaxis of the factors risk.
Keywords: Pregnancy; Porphyria; Porphyrin precursors; Acute crisis.
Colomb Med. 2011; 42: 107-10
Porfiria y gestación. A propósito de un caso
Las porfirias son un grupo de enfermedades producidas por un déficit de las enzimas encargadas de la síntesis del hemo, que pueden dar lugar a un cuadro clínico grave que requiere un diagnóstico precoz para evitar complicaciones. La frecuencia de la enfermedad es baja y su asociación con el embarazo inusual, pero es un buen momento para que las pacientes portadoras desarrollen la enfermedad o sufran una exacerbación de la misma, de ahí la importancia vital de la profilaxis de los factores de riesgo.
Palabras clave: Gestación; Porfiria; Porfirinas; Crisis aguda.
Colomb Med. 2011; 42: 107-10
We, herein, present an unusual case of porphyria diagnosed during the puerperium period in our health care service.
Systematic Medline, PubMed, Cochrane, and uptodate search were done based on the terms pregnancy, puerperium, porphyria, acute crisis during the last five years. We then took the seven most relevant articles according to the qualification of the paper where it was published.
A 34 year old Caucasian woman presented intense abdominal pain during immediate puerperium.
Family background: of no interest
Personal background: allergic to penicillin, pantomicine, and aspirin. The patient is reportedly an ex smoker (ten cigarettes per day). Operated for meningoplasty and uses a prosthetic eyeball, secondary to destruction during the M-11 terrorist attack in Madrid, Spain. She received psychiatric treatment for posttraumatic stress syndrome.
In July 2008, the patient attended emergency room consultation for abdominal pain and also located in the episiotomy. Pain did not respond to pain killers previously prescribed on two occasions. Physical examination revealed a slight indurated episiotomy scar with no signs of infection or hematoma. All tests, including blood count, vital constants, and gynecological ultrasound, were normal. We decided on hospital admission in our service with the following diagnosis: incipient episiotomy infection and treated the patient with antibiotics and pain killers.
During the hospital stay, the patient did not respond to pain killers and was evaluated by psychiatric and anesthesiology services. She was finally diagnosed with adjustment disorder with anxiety and depression features.
Four days later, she was admitted to the intensive care unit after having three episodes of generalized seizures and was treated with phenytoin, midazolam, and manitol after dismissing brain damage and meningitis. The patient was diagnosed with Recurrent Seizures and readmitted to the hospital ward.
During hospitalization, levels of TSH, ACTH, LF, FSH, thyroxine, and cortisol were determined to dismiss Sheehan syndrome; all levels were reported normal.
CT scan was performed because of abdominal-pelvic constipation objecting feces up to rectum-sigma union and distended intestinal bowel loops.
Finally, she began to present a progressive lethargic state with disorientation in time related to severe hyponatremia (109.8 mmol/l). She was then readmitted to the ICU, proposing Acute Neurovisceral Porphyria crisis demonstrated with the following values of porphyrins in urine.
ALA: 40.8 mg/24 h (<7 mg/per day)
PBG: 30.8 mg/24 h (<2 mg/per day)
Total porphyrins (uro/copro) 4424 mg/24 h
(15-300 mg/per day)
Copro-porphyrins 3920mg/24 h (<250)
Uro-porphyrins 504 (<50)
With these results, we started treatment with intravenous infusion of heme alginate, 150 mg/24 h during four days. With non-established porphyria and given the clinical stability, the patient was discharged from the hospital for future follow up.
Porphyrias are a variety of disorders, inherited or not, involving the activity of enzymes involved in the synthesis of the heme group and other hemoproteins. As a consequence of its deficiency, intermediate toxic metabolites build up and are stored in different types of tissues in our body, developing the neurovisceral symptoms like abdominal pain, psychiatric signs, and neurological and photosensitive skin signs.
Diagnosis of each type of deficiency is given by identifying the metabolite produced in excess in the red blood cells, plasma, feces, or urine, as in our case. Most of them can be diagnosed by measuring the exact enzyme activity in the appropriate tissue1. Most mammal cells are able to synthesize heme, although it mostly occurs in the bone marrow, up to 85%.
Frequency is estimated in 1/10.000 but this can vary depending on geography2. Not all carriers of the disease develop clinical findings and there are significant interactions between the defect and environmental factors2.
There are as many porphyrias as enzymes involved in the metabolic route with exception of the first enzyme, a-Aminolevulinic acid (ALA), whose synthesis is increased in compensatory manner as it is normally inhibited by its final product, heme1,3.
We found deficiencies of ALA dehydratase that correlates with acute intermittent porphyria, both with neurological symptoms.
Our case offers some doubts about classification; first, because a second determination of urine porphyrins was made when the patient had already started treatment. In the second place, because our lab results could well determine mixed porphyria that appear to have acute crisis.
After the clinical findings and high incidence, the patient was initially diagnosed as acute intermittent porphyria, also called Swedish porphyria. It is a metabolic error that affects more women than men and is inherited in autosomal dominant manner, causing a partial deficit in the porphobilinogen deaminase enzyme.
Presentation with abdominal pain is well known and up to 95% of these patients start with this symptom. Abdominal symptoms are followed by progressive neuro-psychiatric features (periphery motor neuropathy, breathing paralysis, seizures, or loss of consciousness).
Other clinical findings that can appear during the process are tachycardia, hypertension, and bladder retention; seizures are usually due to severe hyponatremia. It is essential to understand that seizures can occur and that antiepileptic medications can be harmful.
Acute intermittent porphyria should always be considered in the differential diagnosis of abdominal pain presented with neuro-psychiatric features, even if there is a previous family history or not. Once we have the diagnosis, the family should be tested to determine PBGD levels4,5.
Prenatal diagnosis is of interest, especially in determining erythropoietic porphyria. Techniques that may be involved are measuring porphyrins in amniotic fluid and amniotic cell culture1. Genetic counseling is important, specifically when both parents carry the affected gene5. Oral contraceptives should be avoided in patients and first grade relatives, as they can promote acute crisis6.
Treatment is symptomatic and oriented to improving the skin condition and clinical manifestations. It is important to avoid precipitating factors involved in developing acute crisis. Some examples are estrogens, valproic acid, barbiturates, sulfonamides, and hydantoins. Other factors involved in acute crisis are alcohol, hypocaloric diets, and infections5.
The objective of treatment with hematine is to fill up deposits with free-regulating heme. Secondary effects are due to its degradation products. There is also heme arginate, which is more stable with a recommended dose of 2-3 mg/kg/day during four consecutive days administered in slow infusion during 15-20 minutes in a saline solution. Effects on the fetus are unknown; therefore, this treatment should not be used during pregnancy2,5.
Glucose solution is also included in therapy and it is able to stop an acute crisis as it inhibits ALA activity. It should be set up in all conflictive situations like labor, surgery, etc.
As we have described, there are serious difficulties in diagnosing this illness during pregnancy and puerperium. Our patient was misdiagnosed several times4.
Information about porphyria and pregnancy is scant and insufficient. The information we have is from attending on individual cases as the frequency of the affection is low and association with pregnancy is rare. This complicates our knowledge on the behavior of the illness in pregnant patients. What should not be forgotten is that hormonal changes, prolonged fasting due to hyperemesis, and several drugs can initiate an acute porphyrinic attack.
Revision of the literature concludes that the illness can worsen because of symptomatic exacerbations, estimated in 50% of cases7.
Mothers' mortality rates range from 27% to 42.5%7. Symptomatic exacerbations are generally due to exposing the patients to certain drugs that can modify the course of the pregnancy, resulting in abortion, preterm births, and other pregnancy complications. Up to 60% of pregnancy complications happen at the beginning, in early gestational ages2.
Nearly 15% of the complications occur during the second trimester and are generally severe. Although during the last weeks of pregnancy, women present high ALA and PBG levels in urine, in porphyrinic pregnant women the levels tend to be higher3.
An estimated 25% of the complications happen during puerperium. Maximum risks periods seem to be early gestational ages and puerperium. Children from porphyrinic mothers are normal when born, independent of their genotype, although there has evidence of a higher frequency of low birth weight and stillbirths4.
It is important to highlight the possibility of diagnosing this illness during pregnancy and puerperium in fertile women who are carriers of the defect, as this period is of special risk. Diagnosis should be performed by measuring excretion of porphyrins or, better still, by running genetic tests. Thus, we will be able to avoid precipitating factors.
Porphyria can be a negative influence in pregnancy and, in turn, pregnancy can precipitate acute crisis. Women who carry the deficiency should be well informed about risks and receive health information about the symptoms and precipitating factors so they can have healthier pregnancies and healthier children.
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