A 35-year-old woman presented with a slowly progressing asymmetric proximal weakness of both upper and lower limbs for one year. Her left side was noticeably weaker, with accompanying scapular winging. Examination showed normal distal power and preserved deep tendon reflexes. Normal nerve conduction studies, along with an electromyography showing a myopathic pattern, suggested a primary muscle disorder. Clinically, facio-scapulo-humeral dystrophy was suspected. Serum creatine kinase was measured at 2,500 IU/L. On peripheral blood smear, we observed numerous lipid-laden vacuoles inside leukocytes (Jordan’s anomaly), prompting us to order whole-exome sequencing. It identified a homozygous PNPLA2 variant, c.99del (p.Phe35SerfsTer57) - a single-nucleotide deletion predicted to cause a frameshift and a premature stop codon, resulting in loss of normal ATGL function. This led us to the diagnosis of neutral lipid storage disease with myopathy. Despite this truncating mutation, she exhibited a mild, asymmetric, adult-onset disease without hepatic or cardiac involvement, demonstrating an apparent genotype-phenotype discordance.

A simple, cost-effective peripheral smear unmasked a rare metabolic myopathy, confirmed by genetic testing. This case, featuring asymmetrical weakness with scapuloperoneal distribution and a novel PNPLA2 mutation, expands the clinical and molecular spectrum of neutral lipid storage disease with myopathy. It also raises the question of how even truncating mutations in the PNPLA2 gene can present with mild adult-onset disease, prompting further search for alternative mechanisms and potential effect modifiers.