DEMYELINATING NEUROPATHY IN GENETICALLY CONFIRMED ACUTE INTERMITTENT PORPHYRIA

摘要

Wu and colleagues described axonal neuropathy in a cohort of acute intermittent porphyria (AIP) neuropathies, including patient 8 who manifested axonal and demyelinating features. We report the case of a 25-year-old man who developed fatigue, abdominal pain, vomiting, urinary retention, and depression associated with progressive weakness, numbness and paresthesia, dizziness, and palpitation upon taking tinidazole 500 mg daily and rifampin 450 mg on alternate days for 4 weeks until 1 week before onset of neurological symptoms. Examination showed weakness versus firm resistance in proximal and distal limb muscles that was notable for mild partial foot drop on the right, with symmetrical stocking vibratory and cold temperature sensory loss, and hypoactive leg reflexes. The electro-diagnostic (EDX) findings summarized in Table 1 were notable for the presence of asymmetrical motor poly-neuropathy with features of acquired demyelination (abnormal temporal dispersion, partial conduction block, reduced velocities, prolonged distal latencies, and prolonged F-wave latencies) and axonal loss in bilateral fibular and right tibial nerves. Head-up tilting produced symptomatic orthostatic intolerance accompanying a 49 mmHg drop in systolic blood pressure to 78 mmHg with heart rate acceleration of 43 beats per min (bpm) to 137 bpm. Epidermal nerve fiber (ENF) density in the distal calf was 4/mm (5th % reference value, 5 ENF/mm) with uneven distribution and patchy branch drop-out. Sural nerve biopsy showed seg-mental remyelination in 14/50 (28%) teased nerve fibers, and semithin sections showed occasional, thinly myelinated fibers. Underlying soleus muscle showed atrophic myofibers (see Supplementary Figure SI, available online). Cerebrospinal fluid was normal except for protein content of 101 mg/dl (normal, 12-60). The urinary aminolevulinic acid (ALA) was 11.7 uM (normal .09-2.97), and porphobilinogen (PBG) was 24.1 uM (0-1.08). Analysis of the hydroxymethylbilane synthase (HMBS) gene at the Ilq23.3 locus encoding PBG deaminase (PBGD) using polymerase chain reaction amplification of extracted DNA followed by exon-specific primer extension analysis of all exons, exon-intron boundaries (20-30 base pairs), and promoter regions showed a causative missense mutation in exon 3 in the co-factor-binding cleft of PBGD at the R26H locus. Genetic testing failed to identify other affected family members. Antibiotics were discontinued and he had clinical improvement after 4 weeks.