Hypercholesterolemia Successfully Treated With Two Different PCSK9 Inhibitors in a Patient With Glycogen Storage Disease IXd: Phosphorylase Kinase Deficiency.

OBJECTIVE: This case report describes a novel use of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors in a patient whose glycogen storage disease (GSD) was unmasked by statin therapy. Evidence-based guidelines for the management of hyperlipidemia in patients with concurrent neuromuscular disorders (NMD) remain limited.

METHODS: We report the case of a 46-year-old man with hyperlipidemia, treated with simvastatin, who presented with 2 days of thigh pain without weakness or dark urine. He was diagnosed with statin-associated muscle symptoms. On further interview, the patient recalled experiencing thigh muscle soreness decades earlier while in the military, at which time his creatine phosphokinase (CPK) ranged between 1,200 and 3,000 U/L. He admitted not disclosing this history or a prior muscle biopsy.

RESULTS: Muscle biopsy and electromyography/nerve conduction velocity studies were followed by whole-exome sequencing, which demonstrated hemizygosity for c.2369+1 G>T, a pathogenic variant in the PHKA1 gene, consistent with GSD IXd. He was subsequently treated with 2 PCSK9 inhibitors (first evolocumab, then alirocumab). A comprehensive literature review identified only 2 previously reported cases of GSD treated with alirocumab.

CONCLUSION: Even if not volunteered, a history of muscle symptoms should be actively sought before initiating statins, with baseline CPK measurement if indicated. As statins are increasingly prescribed, additional cases of GSD may be unmasked, underscoring the need to define optimal therapy for hyperlipidemia in NMD, including GSD. We propose a specific role for PCSK9 inhibitors in patients with statin intolerance and GSD IXd, which has not been previously reported.