Glycogen storage disease type IX (GSD type IX) is caused by a deficiency in phosphorylase b kinase (PHK) and is classified into hepatic (IXa-c) and muscular (IXd) subtypes. GSD type IXd leads to exercise intolerance, rhabdomyolysis, and myoglobinuria owing to impaired glycogen breakdown. It is a rare and mild metabolic disorder, with only 19 reported cases of PHKA1 mutations. To the best of our knowledge, this is the 1st report on the perioperative management of a patient with GSD type IXd. A 61-year-old male presented with a right inguinal hernia requiring surgical repair. He had experienced muscle weakness since the age of 53, which progressed to severe neck muscle atrophy by the age of 58. Genetic testing confirmed a PHKA1 mutation, leading to the diagnosis of GSD type IXd. He had previously undergone multiple surgeries without any complications. Given his underlying muscle weakness, totally extraperitoneal (TEP) inguinal hernia repair was performed to minimize postoperative pain and muscle damage. Postoperative monitoring revealed no rhabdomyolysis or myoglobinuria, and the patient was discharged without complications on POD 7. We successfully managed a patient with GSD type IXd perioperatively, without complications. Although this disease can cause rhabdomyolysis, the symptoms are often mild and may remain undiagnosed. Therefore, in patients with muscle weakness or elevated creatine kinase levels, careful surgical planning and perioperative monitoring are essential.

Glycogen Storage Disease (GSD) IXd, caused by PHKA1 gene mutations, is an X-linked rare disorder that can be asymptomatic or associated with exercise intolerance. GSD type II is an autosomal recessive disorder caused by mutations in the GAA gene that lead to severe cardiac and skeletal muscle myopathy. We report the first case of co-occurrence of type IXd and type II GSDs in a 53-year-old man with an atypical glycogen storage disease presentation consisting in myalgia in the lower limbs at both rest and after exercise and increased levels of transaminases from the age of 16. At the age of 43, the patient presented a steppage gait, inability to run and walk on his heels, hypotrophy of the pectoral and proximal muscles, reflexes not elicitable, and CK levels 3.6 times the upper reference limit. Next Generation Sequencing (NGS) identified one variant in the PHKA1 gene, c.1360A > G p.Ile454Val (exon 14) inherited by his mother, and two heterozygous variants in the GAA gene, c.784G > A (exon 4) and c.956-6T > C (exon 6). A review of GSD IXd cases reported to date in the literature is also provided.

Glycogen storage disease (GSDs) is characterized by abnormally inherited glycogen metabolism. GSD IXd, which is caused by mutations in the PHKA1 gene, is an X-linked rare disease with mild myopathic symptoms. To date, only 13 patients with GSD IXd have been reported. In this study, we aimed to expand the clinicopathological-genetic spectrum of GSD IXd at a neuromuscular center in China. Data on patients diagnosed with GSD IXd at our neuromuscular center were collected retrospectively. Clinical features, electrophysiology, muscle pathology, and genetic information were analyzed. Between 2015 and 2021, three patients were diagnosed with GSD IXd based on clinical manifestations, pathological findings, and genetic testing. One patient presented with mitochondrial myopathy. All patients exhibited muscle weakness and elevated levels of creatine kinase. Electromyography-detected myopathic changes were found in two patients, whereas one patient refused to undergo this examination. Pathological examinations in all patients revealed subsarcolemmal accumulation of glycogen under PAS staining. All patients had mutations in the PHKA1 gene and the patient with mitochondrial myopathy also had a mutation in the MT-TL1 gene. Our study expands the clinicogenotype and phenotype of GSD IXd in a Chinese population. Our study also expands the known mutation spectrum for GSD IXd, contributing to a better characterization and understanding of this ultrarare neuromuscular disorder.

PHKA1 mutations are causative for glycogen storage disease type IXd (GSDIXd), a myopathy that can be asymptomatic or associated with exercise intolerance, and rarely is accompanied by weakness or atrophy of limbs. Here we report a patient with GSDIXd who developed distal myopathy which was not accompanied by exercise intolerance at age 71. Muscle MRI revealed severe but gradual involvement of muscles with disease progression in the order of medial gastrocnemius, soleus, lateral gastrocnemius, and gluteus muscles. Muscle pathology revealed vacuolar changes with glycogen accumulation, and muscle enzymatic activity of phosphorylase b kinase was markedly decreased to 1.5 nmol of substrate utilized/min/mg protein (normal range: 39.5 ± 10.8). Collectively, the present findings suggest that PHKA1-associated distal myopathy is an adult-onset distal calf dominant myopathy which does not always present with exercise intolerance.