Acute intermittent porphyria presenting as progressive muscular atrophy in a young black man

Abstract

Acute intermittent porphyria (AIP), the most common porphyria affecting the nervous system, typically presents with neurovisceral crises followed by a motor neuropathy. We describe an unusual presentation in a young man with molecularly confirmed AIP. Case presentationA 23-year-old university student was referred to Groote Schuur Hospital, Cape Town, South Africa, with suspected motor neuron disease. Over the preceding year he had noticed insidious progressive weakness of both upper limbs. Initially, the weakness affected grip strength bilaterally, but within 9 months progressed to also involve proximal arm function. Ten months after onset, he developed profound leg weakness over a period of days, rendering him unable to walk without support. He had no bowel or bladder sphincter involvement and no bulbar symptoms, but complained of a weak cough. He had not experienced any neuropsychiatric symptoms or abdominal pain.Examination showed a thin and wasted man with marked amyotrophy involving all four limbs, both proximally and distally (Fig. 1). He was bed-bound, and unable to turn in bed, feed or dress himself. He had mild symmetrical facial weakness and a weak cough with a reduced vital capacity (<80% of expected). He had truncal weakness and a flaccid quadriparesis, but no fasciculations were noted: upper limb strength Medical Research Council (MRC) grade 1/5 proximal, 2/5 distal; lower limb strength 2/5 proximal, 3/5 distal. He was areflexic in the legs with either hyporeflexia (biceps and supinator reflexes) or areflexia (triceps reflexes) in the arms. Findings on sensory examination were normal apart from a patch of reduced sensibility for pinprick and touch over the left anteromedial thigh region. CLINICAL Corresponding author: C H Albertyn (christine.albertyn@uct.ac.za)Acute intermittent porphyria, the most common porphyria affecting the nervous system, typically presents with neurovisceral crises followed by a motor neuropathy. We describe a 23-year-old black South African man presenting with a progressive stuttering, lower motor neuron syndrome developing over months. He had not experienced pain or neuropsychiatric symptoms. One year after symptom onset he was bed-bound with a flaccid quadriparesis. There was marked amyotrophy, but without fasciculations. Sensation was intact apart from a hypo-aesthetic patch over the thigh. Electrophysiological investigations showed an active motor axonopathy. Urinary porphyrins, δ-aminolaevulinic acid and porphobilinogen were elevated. Mutation analysis revealed the c445C>T (R149X) mutation in the porphobilinogen deaminase gene. The patient responded dramatically to haem arginate and could walk with assistance 2 weeks later. We identified the first molecularly confirmed acute intermittent porphyria in a black South African. The clinical presentation mimicked a progressive lower motor neuron syndrome.

Molecular characterisation of acute intermittent porphyria in a cohort of South African patients and kinetic analysis of two expressed mutants

“…The p.Arg195Cys and p.Gly236Ser mutations were found in Black patients, but have been previously described in a cohort of Finnish12 and French19 patients with AIP, respectively. The p.Arg149X mutation in exon 9, which creates a premature stop codon, was identified in a Black patient whose clinical phenotype has previously been reported 20. This mutation has also been found in Finnish families 12.…”

Severe porphyric neuropathy - importance of screening for porphyria in Guillain-Barré syndrome

“…In the same study, several other patients with pre-existing neuropathy deteriorated markedly at the onset of a new attack, but the weakness resolved rapidly after haemin administration. [7] One patient with AIP improved even after a long period of being bedridden when a course of haemin was given, [14] and other authors similarly report a favourable outcome after haemin administration. [15] Unfortunately, the administration of haemin was delayed in most of our patients owing to local unavailability of the drug, which may have worsened the outcome, since studies recommend early administration of haemin [7,16] to limit or reverse the toxic effects of haem precursors on the peripheral nerves.…”

Neuralgic Amyotrophy Syndrome with Widespread Myokymia

“…9 It was important to exclude acute intermitted porphyria as this may present as a motor neuron disease mimic with rapidly developing severe atrophy. 10 Corticosteroid therapy was used in a small open-label study, most frequently within 10 days of symptom onset, although the average was 30 days. Those receiving prednisone suffered more pain and greater disability compared to those not given prednisone.…”