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Table of Contents
CLINICAL ARTICLE
Year : 2021  |  Volume : 22  |  Issue : 1  |  Page : 16-21

Acute intermittent porphyria - A case presentation


Associate Professor, College of Nursing, Christian Medical College, Vellore, Tamil Nadu, India

Date of Submission23-Jun-2020
Date of Decision05-Sep-2020
Date of Acceptance10-Oct-2020
Date of Web Publication07-Jul-2021

Correspondence Address:
Mrs. Sasikala R Umesh
College of Nursing, CMC, Vellore, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJCN.IJCN_36_20

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  Abstract 


Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disorder affecting the production of haem, resulting from deficiency of porphobilinogen (PBG) deaminase. It is the most common form of acute porphyrias. The major symptom of an acute attack is abdominal pain, often accompanied by vomiting, hypertension and tachycardia. Attacks are most common in young women but rare before puberty or after menopause. Severe acute attacks may require hospitalisation. The most common triggers for acute attack are medications, weight loss, diet and surgery. Elevated urine PBG confirms the diagnosis of AIP. The treatment for acute porphyria includes administering intravenous haemin or glucose. This article outlines the disease process and its management. A case report is presented focusing on the nursing management of a patient with AIP using nursing process approach.

Keywords: Acute intermittent porphyria, autosomal dominant, porphobilinogen deaminase


How to cite this article:
Umesh SR. Acute intermittent porphyria - A case presentation. Indian J Cont Nsg Edn 2021;22:16-21

How to cite this URL:
Umesh SR. Acute intermittent porphyria - A case presentation. Indian J Cont Nsg Edn [serial online] 2021 [cited 2021 Dec 1];22:16-21. Available from: https://www.ijcne.org/text.asp?2021/22/1/16/320823




  Introduction Top


Porphyrias are inborn errors of metabolism caused by a deficiency of enzymes involved in haem synthesis. The haem synthesis pathway is a multistep process that involves a specific enzyme at every step. Each subunit of haemoglobin is a globular protein containing an embedded haem group that contains one iron atom, capable of binding one oxygen molecule. Porphyrins are precursors of haem, an essential component of haemoglobin.[1] A characteristic feature of porphyria is the excretion of porphyrins and porphyrinogens in urine.[2] Porphyrias are generally classified into two groups based on where the excess precursors originate: the “hepatic” and “erythropoietic” types.[3],[4] Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by deficiency of enzyme: hydroxymethylbilane synthase (HMBS), also known as porphobilinogen deaminase (PBGD), the third enzyme in the haem biosynthesis pathway. AIP is an acute, hepatic form of porphyria. Approximately 3%–5% of affected individuals, predominantly women, experience recurrent attacks which are more than 4 per year for a period of many years.[3] The course and severity of attacks are highly variable from one person to another. Rapid, accurate diagnosis is important. Delays in diagnosis may result in permanent neurological damage or death.

Incidence

It is estimated that it affects 1 per 500–50,000 people.[3] AIP affects women to a greater degree than men, with a ratio of between 1.5 to 2:1. Attacks are rare before puberty. The typical age for the appearance of symptoms is between 18 and 40 years.[1] In Europe, the prevalence of symptomatic AIP is reported to be 5.9 per million people in the general population. The prevalence may be similar in most of the other countries in the world. AIP can occur in individuals of all ethnic backgrounds, although it may be less frequently reported in African-American individuals.[3],[4]


  Classification Top


Porphyrias are classified as follows:[5]

A simpler classification system distinguishes porphyrias as acute or cutaneous:

  1. Acute porphyrias: Porphyrias that cause neurologic, mental and abdominal symptoms.


    • AIP – the most common form
    • Variegate porphyria (VP)
    • Hereditary coproporphyria (HCP)
    • Delta-aminolevulinic acid (ALA) dehydratase deficiency porphyria, which is extremely rare.


  2. Cutaneous porphyrias: Porphyrias that cause skin symptoms, when the skin is exposed to sunlight.


Another classification system is based on where the excess precursors originate:

  1. Hepatic porphyrias: Precursors originate primarily in the liver
  2. Erythropoietic porphyrias: Precursors originate primarily in the bone marrow.



  Causes and Triggers Top


AIP is a multifactorial disorder. Several factors such as genetic and environmental factors in combination play a major role.[3]

AIP is caused by a deficiency of PBGD. The PBGD enzyme deficiency is caused by a mutation in the HMBS gene which is inherited as an autosomal dominant trait. However, the majority of people with a mutation in this gene do not develop symptoms of AIP and additional factors – “triggers” are also required to cause symptomatic acute porphyria. Triggers include certain drugs (barbiturates, sulpha antibiotics, contraceptives and anti-seizure), excessive alcohol consumption, fasting or dieting, stress, infections or certain hormonal (endocrine) factors. The diagnosis of AIP gets delayed due to non-specific symptoms and similarities with other diseases.[1],[6]


  Pathophysiology Top


In AIP, over 100 mutations have been identified on the long arm of chromosome 11 at the HMBS gene, which codes for the cytoplasmic enzyme PBGD.[5] Mutations in the HMBS gene lead to 50% deficient levels of PBGD in the body. This deficiency is noticeable in the acute attacks, where the haem pool in the liver gets used, and there is the induction of delta-ALA synthase 1 (ALAS1). This process leads to the accumulation of delta-ALA and porphobilinogen (PBG), which are the immediate precursors proximal to the HMBS [Figure 1]. In AIP, the neurologic damage occurs due to the accumulation of the porphyrin precursors, PBG and ALA. The AIP-associated neurological damage manifests as peripheral, autonomic neuropathies and psychiatric manifestations. The exact mechanism by which elevated levels of PBG and ALA lead to symptomatic disease is unclear as many patients with this genetic defect in spite of having a high porphyrin secretion remain asymptomatic.[1],[7]
Figure 1: Pathophysiology of Acute Intermittent Porphyria

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  Signs and Symptoms Top


A patient may present with:[8]

  • Gastrointestinal symptoms
  • Abdominal pain – It is the most common symptom and often the initial sign of an attack
  • Pain is usually severe, steady and widespread. Less often, it is cramping in nature
  • Pain may also occur in the neck, lower back, buttocks, arms and legs. Nausea, vomiting, constipation or diarrhoea and abdominal distension are also other symptoms that are often seen.
  • Cardiovascular symptoms: Cardiac arrhythmias and hypertension
  • Urinary symptom: Urinary retention
  • Neurological symptoms: Acute peripheral neuropathies including numbness or tingling and burning sensations that usually begin in the feet and may progress to affect the arms and the trunk, eventually causing partial loss or impairment of motor function and life-threatening respiratory failure
  • Seizures: Hyponatraemia may develop rapidly during an attack and contribute to the onset of seizures.
  • Psychological symptoms: Irritability, depression, anxiety, insomnia, hallucinations, paranoia, disorientation and altered consciousness.[8]



  Complications Top


Long-term complications include:[9]

  • Depression: Particularly anxiety is more common amongst individuals with AIP
  • Hepatocellular carcinoma: Individuals with AIP appear to be at increased risk of developing primary HCC, usually after age 54 years
  • Renal dysfunction: Approximately 70% of individuals with recurrent attacks will develop progressive renal dysfunction
  • Recurrent acute attacks: Approximately 3%–8% of individuals with AIP, mainly women, experience repeated attacks.[9]



  Related Disorders Top


The acute attacks that characterise AIP are similar to those seen in three other forms of porphyria, specifically VP, HCP and ALA-dehydratase deficiency porphyria, and also a few other conditions.[9]

  • Tyrosinaemia type I is a rare autosomal recessive genetic metabolic disorder characterised by lack of the enzyme fumarylacetoacetate hydrolase, which is needed for the final breakdown of the amino acid tyrosine. Failure to properly break down tyrosine leads to abnormal accumulation of tyrosine and its metabolites in the liver, including a haem precursor ALA, potentially resulting in severe liver disease
  • Lead toxicity can cause symptoms that mimic acute porphyria. Lead inhibits several of the enzymes of haem biosynthesis, which can therefore result in an increase in urine coproporphyrin and 5-ALA excretion but not PBG excretion
  • Guillain–Barré syndrome is a rare, rapidly progressive disorder causing muscle weakness, sometimes progressing to complete paralysis.[9]



  Diagnosis Top


Diagnosis is usually based on identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and specialised tests.[6]

Clinical testing and workup

  1. Urine studies:


    • Elevated PBG confirms the diagnosis of AIP: A positive test is indicated with an increase of five times normal
    • Elevated ALA excretion
    • Presence of dark or reddish urine.


  2. Faecal studies: Porphyrin levels are normal in AIP but elevated in HCP and VP
  3. Family testing: Molecular genetic testing to detect mutation in the HMBS gene.



  Treatment Top


Owing to the simulation of symptoms of AIP by several abdominal, metabolic and neuropsychiatric conditions, establishing a confirmed diagnosis forms the core of the management of AIP.[10],[11]

  1. Avoidance of precipitants, especially drugs, requires extreme emphasis on preventing acute attack
  2. Medical management to decrease the number of porphyrins or porphyrin precursors produced in the liver


    • Administration of dextrose and high-carbohydrate diet: This is typically recommended


      • During acute attack (abdominal pain, vomiting, hyponatraemia and neurovesical attack), administration of 10% dextrose in 0.45% saline intravenously should be initiated immediately to inhibit hepatic ALAS1 transcription
      • If the symptoms are not acute, a trial of a high carbohydrate diet (carbohydrate intake should be 55%–60% of total energy intake) for 48 h before starting specific treatment is recommended.


    • Haemin (panhaematin and haem arginate) is the drug of choice


      • Intravenous haem therapy should be administered without delay in severe acute attacks and maintained for 4 days (3–4 mg/kg of haem/day). It replenishes the hepatocyte haem pool and downregulates ALAS1, resulting in reduced production of porphyrin precursors and corresponding improvement in symptoms.


    • Cimetidine: It is effective for acute porphyric crisis and for long-term management.

      Recommended oral dosage is 800 mg/day. Cimetidine has a role in prophylaxis of acute episodes by maintaining a baseline suppression of ALA synthase activity. Cimetidine should be reserved for use only after standard treatment modalities have failed.


  3. Symptom management


    • Pain: It is severe and often requires the use of opiates
    • Nausea: It can be severe. Nausea and vomiting are controllable with phenothiazine drugs and ondansetron. These symptoms usually start lessening in 72–96 h
    • Gabapentin: In cases where seizure or neuropathy is present
    • Seizures: Barbiturates must be avoided. Benzodiazepines are safe, when used in conjunction with gabapentin
    • Tachycardia and hypertension: Preferred medications are beta-blockers, angiotensin-converting enzyme inhibitors and calcium channel blockers
    • Depression: This symptom is common, especially with repeated attacks. Treating the offending symptoms and if needed the judicious use of antidepressants are recommended.


  4. Hormone administration: Hormonal fluctuations that contribute to cyclical attacks in women have been treated with oral contraceptives and gonadotropin-releasing hormone analogues such as leuprolide
  5. Fluid and electrolyte replacement: Hyponatraemia should be corrected with intravenous saline solutions
  6. Liver transplantation: Individuals with severe disease who have failed to respond to other treatment options may need to undergo liver transplantation.[10],[11] A liver transplant in individuals with AIP is an option of last resort.



  Case Report Top


Ms. A, a 25-year-old unmarried woman, was apparently well till 7 years ago. She was hospitalised with a history of 8–9 episodes of vomiting per day (post-prandial, non-bilious and non-bloody) and constipation for the past 7 years, associated with a diffuse non-radiating abdominal pain with no relieving or aggravating factors. She also had generalised weakness in the lower limb with inability to stand or walk and wobbling of knees for 10 days. On admission, she was conscious and well oriented. Physical examination revealed a heart rate of 64/mt, blood pressure (BP) of 100/70 mmHg and a respiratory rate of 20/mt. The abdomen was soft, but a diffuse tenderness was present without any organomegaly or free fluid. Mild motor weakness (Grade 4) in bilateral hips and knees has been elicited. Gastroscopy and intestinal biopsy showed mild chronic active duodenitis and gastritis. Gastric emptying study showed significant delayed gastric emptying (274 mts). During her stay in the hospital, she experienced acute abdominal pain and worsening of motor deficits. Urine PBG was elevated in all three samples (1200 mg/24 h urine collection). Initially, she was started on sucrose aqua gel, three times a day injection dextrose 50%100 mL IV q6 h and injection DNS q4 h. She was given sugar and glucose water as tolerated. She was offered easily digestible high carbohydrate diet. Later, she was administered injection haemin 4 mg/kg/day (200 mg/day) for 4 days as intravenous infusion over 30 min each. After the treatment, her motor power improved and uroporphobilinogen value came within normal limits. She was explained about possible good prognosis with early detection and management, especially if acute attacks are identified and managed early and further attacks are prevented.


  Nursing Management Top


1. Nursing Diagnosis

Acute abdominal pain, related to dysfunction of peripheral nervous system, secondary to elevated PBG.

Expected outcome

Abdominal pain is minimised as evidenced by verbalisation of reduction in pain <2 in the Numerical Rating Scale.

Interventions

  • Assessed the characteristics of pain such as site, frequency, intensity, aggravating and relieving factors
  • Offered comfortable position with comfort devices
  • Administered tablet paracetamol 1 g as needed
  • Offered emotional support.


Evaluation

The pain was minimised as evidenced by reduction in pain score to < 2/10 in the Numerical Rating Scale. She expressed her increased comfort level.

2. Nursing Diagnosis

Imbalanced nutrition less than body requirement related to vomiting and abdominal pain secondary to delayed gastric emptying.

Expected outcome

Nutritional status is improved as evidenced by no reduction in her weight, normal serum glucose level and improved well-being.

Interventions

  • Assessed the nutritional status


  • Body mass index (BMI) was checked (on admission 17 kg/m2, 3 weeks later remained as 17 kg/m2)
  • Nutritionist consultation was obtained
  • Provided her with easily digestible high calorie predominantly carbohydrate diet according to her tolerance, in the form of liquid (glucose water and sugar water) followed by soft diet like bread, porridge, banana and milkshakes
  • Frequent small meals were encouraged
  • Ensured adequate oral hygiene
  • Administered injection ondansetron 8 mg as needed, tablet pantoprazole 40 mg, OD and tablet itopride 50 mg, TID
  • Administered tablet sucrose aqua ge1, TID and injection dextrose 50% 100 mL IV q6 h
  • Administered injection dextrose normal saline one pint every 4 h during acute phase
  • Administered injection haemin 1 amp – 200 mg/day reconstituted in 100 ml normal saline over 30 mts, followed by 100 ml normal saline over 30 min for 4 days
  • Strict intake and output was maintained.


Evaluation

There was no decline in BMI during her hospitalisation. Her oral intake and tolerance improved. The blood sugar values remained within normal limits.

3. Nursing Diagnosis

Risk for fluid volume and electrolyte deficit related to vomiting secondary to delayed gastric emptying.

Expected outcome

Normal fluid volume and electrolyte levels are maintained as evidenced by systolic BP ≥90 mmHg, HR 60–100 beats/min, intake and output cumulative balance and electrolyte values within normal range.

Interventions

  • Monitored vital signs
  • Monitored intake and urine output
  • Assessed the vomitus for colour, content and quantity
  • Administered injection ondansetron 8 mg as needed, tablet pantoprazole 40 mg, OD and tablet itopride 50 mg, TID
  • Ensured intake of glucose and sugar water at small volume frequently
  • Administered injection DNS one pint every 4 h.


Evaluation

During acute phase Ms. A was given parenteral fluid and later oral glucose and sugar water. She did not develop fluid volume deficit. Her electrolyte values were within normal limits.

4. Nursing Diagnosis

Impaired physical mobility related to generalised weakness and wobbling of knees secondary to neurotoxic effect.

Expected outcome

Physical mobility is achieved as evidenced by independence in walking and performing daily activities of living.

Interventions

  • Assessed her mobility status
  • She was assisted for ambulation
  • She was helped to take bath and to meet other toilet needs
  • Ensured specific treatment measures (specifically haemin therapy) are carried out on time as ordered.


Evaluation

Ms. A was dependent on her activities of daily needs in the beginning of her hospitalisation. After completion of haemin therapy, improvement was noted in her motor power. She was independent, and she was walking without assistance.

5. Nursing Diagnosis

Constipation related to vomiting and poor food intake secondary to delayed gastric emptying.

Expected outcome

Normal elimination pattern is maintained as evidenced by regular bowel movement.

Interventions

  • Assessed the bowel movement
  • Administered stool softener syrup cremaffin as per order
  • Assisted in ambulation
  • Administered glycerin enema when necessary.


Evaluation

Ms. A had constipation, and she was administered syrup cremaffin 15 ml hsod and glycerin enema prn till her discharge.

6. Nursing Diagnosis

Risk for ineffective coping individual and family related to the nature of disease.

Expected outcome

Effective coping is enhanced as evidenced by following the given instructions and adhering to the treatment and positive attitude towards treatment.

Interventions

  • Developed good rapport
  • Allowed to ventilate their feelings
  • Exercised active listening skill
  • Explained the nature of disease and management
  • Cleared their doubts
  • Exercised non-judgmental attitude
  • Provided spiritual support and counselling
  • Organised consultation with psychiatrist.


Evaluation

Ms. A and their family members were depressed at the time of admission since Ms. A was not diagnosed at the earliest. After the confirmatory diagnosis, treatment and adequate support and counselling their coping improved.

7. Nursing Diagnosis

Deficient knowledge regarding the disease condition, prognosis and treatment

Expected outcome

Learning needs are met as evidenced by verbalisation of understanding about the condition, prognosis, treatment plans and cooperation with the therapy and care provided.

Interventions

  • Assessed the level of knowledge
  • Facilitated a meet with her treating physician for a detailed explanation regarding the disease condition, treatment plans and prognosis
  • Health teaching was given on the following aspects: High carbohydrate diet, avoiding triggers, especially harmful medications and lifestyle factors such as drinking alcohol, smoking and use of marijuana, prevention of infection, management of acute attack, regular check-up and potential complications.


Evaluation

Ms. A and her family members demonstrated confidence towards disease process and care.


  Conclusion Top


AIP is one of the four types of porphyrias that presents as an acute attack. 90% of the individuals are asymptomatic, while an estimated 5% of affected individuals experience repeated attacks. Affected individuals usually recover from an attack within days. However, if an acute attack is not diagnosed and treated promptly, recovery can take much longer, weeks to months. Haemin is the treatment of choice during an acute attack. Haemin is not a curative treatment but can shorten attacks and reduce the intensity of an attack. Patients and family members who have inherited AIP should be counselled on how to limit their risk of any future acute attacks.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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3.
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5.
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  In this article
Abstract
Introduction
Classification
Causes and Triggers
Pathophysiology
Signs and Symptoms
Complications
Related Disorders
Diagnosis
Treatment
Case Report
Nursing Management
Conclusion
References
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