A Triple Threat: Acute Intermittent Porphyria Presenting with SIADH and Hypertensive Encephalopathy in a Child: A Case Report

Acute intermittent porphyria (AIP) is caused by a hereditary error in porphyrin metabolism, which is characterized by an increase in delta-aminolevulinic acid synthase activity and a deficiency of porphobilinogen deaminase, two vital enzymes needed for the synthesis of heme. Patients may have nausea, vomiting, constipation, muscle weakness, and neuropsychiatric symptoms during an attack [1]. The autonomic, peripheral, and central nervous systems may be impacted. In symptomatic patients, the incidence of neurological symptoms is a very modest 5–17% [2]. If any acute attack occurs, it may result in acute peripheral neuropathy and/or severe encephalopathy in a matter of weeks [3]. Abdominal pain continues to be the most prevalent clinical symptom of AIP. It is frequently widespread and linked to nausea, vomiting, and constipation. It is usually not relieved by painkillers and occurs due to intestinal spasms from autonomic dysfunction [4]. It is necessary to recognize the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) as a sign of an acute porphyria attack since it is thought to be a common cause of hyponatremia in AIP [5]. We present the case of a paediatric patient with AIP complicated by hypertensive encephalopathy in setting of hyponatremia from SIADH. We go over the clinical presentation, diagnostic workup, treatment approaches, and the significance of taking SIADH and hypertensive encephalopathy into account when making a differential diagnosis for individuals with AIP. Informed consent was taken from the parents of the patient and the CARE checklist was followed during the whole course of writing the report.

A 10-year-old girl presented to the clinic with a history of recurrent abdominal pain, vomiting, irritability, anorexia, confusion, and hallucinations with recurrent hospitalizations for at least 10 days per month presented with seizure like episode and altered mental status. Physical examination showed a pale looking girl with an emaciated appearance, afebrile but hypertensive to 185/110. Blood tests showed hyponatremia (sodium levels <135mmol/L) on several occasions with worsening on IV hydration, low serum osmolality with normal urine osmolality consistent with the SIADH. The serum lipase, amylase, Thyroid function tests (TFTs), and plasma parathyroid levels were unremarkable. Cerebral imaging was done to assess potential central nervous system causes of seizures. Magnetic resonance imaging (MRI) and computed tomography (CT) scans showed no acute abnormalities. Then electroencephalography (EEG) was done to evaluate the patient’s seizures and assess for potential epileptic activity, which confirmed the presence of generalized tonic-clonic seizure pattern. Urine was dark brown red in color and was sent for further evaluation revealing elevated urinary porphobilinogen (PBG) (9.5mg/24hr) concerning for AIP. The serum and urine laboratory analysis results of the patient are mentioned in (Table 1). After the confirming diagnosis of SIADH in setting of AIP, leading to hypertensive encephalopathy. Patient was treated with Glucose (500 mg), Captopril (25mg), Bisoprolol Fumarate (5mg), Amlodipine (5mg), and Gabapentin with significant improvement. Patient remains adherent to medication leading to significant reduction in recurrence rate.

Table 1: Serum and Urine Laboratory Analysis.Serum and Urine Laboratory Analysis.

AIP is a metabolic disorder that disrupts the heme biosynthetic pathway and has an autosomal dominant mode of inheritance [6]. It occurs due to a genetic defect in the third enzyme i.e., Hydroxymethylbilane Synthase (HMBS) also known as Porphobilinogen Deaminase of the heme synthesis pathway leading to the accumulation of toxic heme metabolites in the liver [7]. The two most frequent triggers for acute attacks of AIP are medication and surgery [8]. These triggers lead to the accumulation of aminolevulinic acid (ALA) and porphobilinogen (PBG) which are responsible for many clinical symptoms of AIP. The patients initially present with nausea, vomiting, fatigue, dizziness, and weakness. Afterward, the patients develop severe acute abdominal pain which is one of the main symptoms of AIP [9]. Both the peripheral and central nervous systems are involved, which results in neurological symptoms [6]. Pain in the back and extremities, respiratory paresis, cranial neuropathy, weakness, and neuropathic sensory loss are all possible side effects of peripheral neuropathy [10]. Seizures, coma, blurred vision, nystagmus and cerebellar ataxia, PRES, and SIADH are all brought on by the involvement of the central nervous system [11]. PRES was ruled out in our patient owing to clear imaging studies i.e. MRI and CT scans.

Patients with AIP-associated PRES are predominantly female and according to a study, the average age of PRES at presentation was 44 years [12]. Hence, it occurs later in the disease course and is unlikely to be present in our patients. About 20-60% of AIP patients develop SIADH which manifests as hyponatremia in labs. Our patient also had SIADH with concomitant hyponatremia. As SIADH is one of the potential causes of hypertension, there is a possibility that our patient developed hypertension at this young age due to SIADH, which then further led to hypertensive encephalopathy. Also, the majority of patients with AIP have autonomic dysfunction leading to clinical manifestations such as abdominal pain, nausea, vomiting, dizziness, and constipation [13]. This autonomic dysfunction can lead to hypertension which in turn might lead to hypertensive encephalopathy precipitating PRES and seizures [14]. There are also certain psychiatric manifestations of AIP which include anxiety, depression, agitation, hysteria, and psychoses [15]. They also have altered levels of consciousness ranging from somnolence to coma. It is usually diagnosed when the patient has dark urine and elevated urinary porphobilinogen levels along with the typical symptoms of AIP. Certain groups, such as those descended from Northern Europe, have a higher frequency of AIP; as is the case in Sweden [16].

Various epidemiological studies on AIP have shown varying prevalence rates in different countries. AIP has a prevalence of 1 in 20,000 according to European studies [17]. The estimated prevalence of AIP in Pakistan is between 1 and 8 cases per 100,000 people. The goal of therapy should be to terminate an acute attack as quickly as possible and to give the patient supportive and symptomatic treatment. The patient should be started on Hemin, which is an iron-containing porphyrin that limits the activity of delta-aminolevulinate synthase which slows down the heme synthesis pathway, and the accumulation of its intermediates is reduced [18]. The patients should also be given Glucose preparations along with adequate nutrition and fluid therapy. The patients should also be given symptomatic treatment to manage the autonomic dysfunction. It is advised to eliminate triggers that precipitate AIP for both acute and chronic management, and the patients are allowed to avoid these triggers in the future.

AIP is a rare genetic disorder that develops due to a defect in the heme biosynthetic pathway. Although it is rare, it should be considered on the list of differential diagnoses in patients who present with severe abdominal pain, seizures, and SIADH with concomitant hyponatremia to prevent long-term complications. The autonomic dysfunction in AIP should also be considered as a possible cause of hypertensive encephalopathy.

The authors declare no conflict of interest related to publication of this case report.

We sincerely thank the patient for her willingness to participate in this case report.

CARE checklist was followed during our study.

Not Applicable.

Informed consent from the parents of the patient was obtained for the conduction of the study, and the publication.

Consent for publication was obtained.