A 35-year-old woman presented with weeks of tingling and weakness in her legs, a case initially appearing straightforward but proving stubbornly resistant to expected treatment. The diagnostic journey highlights the importance of considering rare conditions, even when initial assessments point elsewhere.
The patient, Ms. P., first noticed tingling in her feet and lower legs approximately three weeks before seeking medical attention. This progressed to difficulty walking and a noticeable weakness in her legs, impacting her ability to lift her feet properly. Concerned by these developments, she promptly consulted a neurologist.
Initial Assessment and Investigations
The neurological examination revealed distal weakness in both legs, accompanied by mild sensory symptoms. Initial investigations included blood tests, magnetic resonance imaging (MRI) of the spine, and a lumbar puncture to examine cerebrospinal fluid. The MRI showed only mild degenerative changes, consistent with age, and no nerve compression or inflammation. Blood tests were largely unremarkable, showing only mild anemia. The cerebrospinal fluid analysis did not reveal any significant abnormalities.
These findings initially suggested Guillain-Barré syndrome (GBS), an autoimmune disorder affecting the peripheral nerves. However, the absence of a characteristic increase in protein levels in the cerebrospinal fluid – known as cytoalbuminaric dissociation – raised doubts. Despite this, GBS remained the most likely diagnosis, and treatment was initiated.
Treatment and Escalating Concerns
Ms. P. Received intravenous immunoglobulins (IVIG), an antibody concentrate intended to modulate the immune response, followed by plasmapheresis, a procedure to remove potentially harmful antibodies from the blood. Unfortunately, neither treatment yielded improvement. Her paralysis progressively worsened, extending to her arms, and she required admission to the intensive care unit and ultimately intubation due to weakness affecting her swallowing muscles.
The lack of response to treatment prompted a reassessment of the diagnosis. An observant intern noticed the patient’s urine had turned a dark red color, a finding not attributable to blood or urinary tract infection. Recalling the patient’s history of abdominal pain and fever preceding the neurological symptoms, and her recent initiation of intermittent fasting, the intern began to suspect a different underlying cause.
The Correct Diagnosis: Acute Intermittent Porphyria
Further testing revealed significantly elevated levels of porphobilinogen and delta-aminolevulinic acid in the urine, strongly suggesting acute intermittent porphyria (AIP). Genetic confirmation followed. AIP is a rare genetic disorder affecting the heme biosynthetic pathway, leading to the accumulation of toxic metabolites when the body’s need for heme increases.
Treatment was switched to glucose infusions and heme-arginine, which provide the necessary building blocks for heme synthesis and help alleviate the buildup of toxic intermediates. With this targeted therapy, Ms. P.’s paralysis gradually improved over several months, allowing her to regain her mobility.
Understanding Acute Porphyria
Acute porphyrias, including AIP, are a group of rare disorders characterized by enzymatic defects in the heme biosynthetic pathway. Patients often present with acute, debilitating, and potentially life-threatening attacks triggered by factors such as medications, hormonal changes, starvation, and infections. According to the National Center for Biotechnology Information (NCBI), these attacks can include severe abdominal pain, weakness, nausea, vomiting, and neurological symptoms.
AIP, the most common of the acute hepatic porphyrias, is caused by a deficiency in the enzyme hydroxymethylbilan synthase, leading to the accumulation of porphyrin precursors. While the genetic defect is present in many individuals, only a fraction develop symptomatic attacks. Symptoms can vary widely and may include psychiatric disturbances, hypertension, and hyponatremia (low sodium levels).
The Importance of Diagnostic Vigilance
This case underscores the critical importance of maintaining diagnostic vigilance and considering rare conditions, particularly when standard treatments fail to produce the expected results. While it is reasonable to initially focus on more common diagnoses, clinicians must be prepared to reassess their assessments and explore alternative explanations when faced with persistent discrepancies. Rare diseases, while individually uncommon, collectively represent a significant proportion of undiagnosed illnesses.
The case also highlights the value of careful observation and attention to seemingly minor clinical details, such as the unusual color of the patient’s urine, which ultimately provided the crucial clue leading to the correct diagnosis. Recognizing these subtle signs can be the key to unlocking a timely and effective treatment plan.
Image source: Midjourney
