A Rare Clinical Presentation of Variegate Porphyria

BACKGROUND: Variegate porphyria is a rare heme biosynthesis disorder caused by pathogenic variants in the PPOX gene. Despite being relatively well characterized, its clinical manifestations are highly variable and can mimic a broad spectrum of neurological and systemic conditions. CASE PRESENTATION: We report the case of a young woman with recurrent episodes of muscle weakness, sometimes accompanied by respiratory dysfunction. Initially suspected to have myasthenia gravis, laboratory testing for this condition was negative. Whole-genome sequencing identified a heterozygous pathogenic variant c.338G>C in the PPOX gene and a homozygous variant of uncertain significance c.190G>A in MYMK, with no other disease-causing variants detected in genes associated with congenital myasthenic syndromes or periodic paralysis. CONCLUSION: In the described case, the patient's atypical clinical manifestations led to a prolonged and complex diagnostic workup. WGS findings suggested possible co-occurrence of variegate porphyria with a potential overlap with a Carey-Fineman-Ziter syndrome. This case highlights the importance of comprehensive evaluation of the clinical presentation in patients with unexplained neuromuscular symptoms.