The coexistence of common and rare conditions in a single person may represent a diagnostic challenge. We herein report the case of a young gentleman diagnosed with an acute HIV infection who had a history of myalgias and exercise intolerance and experienced elevated creatinine and phosphokinase enzyme levels. A 24-year-old gentleman was diagnosed with an acute HIV in May 2023 (HIV-RNA > 10.000.000 copies/ml, CD4+ count 417 cell/L) and started same-day combinarion antiretroviral therapy, cART, with darunavir/cobicistat/tenofovir alafenamide/emtricitabine+dolutegravir), switching to dolutegravir/lamivudine once undetectable, 6 weeks after. After 5 months, he was hospitalized with fever, headache, and acute renal failure (creatinine 500 umol/L). Later, CPK peaked at >22,000 mg/dl. He denied chemsex/drug use and had recently started exercising on a regular basis. HIV-RNA was undetectable, cerebrospinal fluid (CSF) examination was unremarkable. cART was temporarily stopped with the normalization of labs. After 20 days, cART was restarted, as well as physical activity, with relapse of the symptoms requiring rehospitalization. Workups for autoimmune and infectious causes were negative. Suspecting drug-related myositis (data on myopathies under integrase inhibitors have been reported), muscle MRI, muscle biopsy, genetic analyses, hair analysis were performed. He tested positive for cocaine and amphetamines. Muscle biopsy showed type 1 fiber atrophy while muscle magnetic resonance imaging was unremarkable. In January 2025, genetic testing came back confirming type VII glycogenosis. This case highlights the diagnostic complexity of rare metabolic disorders, especially when coexisting with acute HIV, continuous medication use and drug exposure. It allows us to highlight the importance of considering rare metabolic disorders as differential diagnoses, as they can mimic systemic illnesses or drug-related effects. Glycogen storage diseases (GSDs) are inherited inborn errors of carbohydrate metabolism that result in abnormal glycogen storage. The onset can range from neonatal life to adulthood, and clinical manifestations result either from a failure to convert glycogen into energy or the toxic accumulation of glycogen.  Glycogen is a branched polymer comprised of glucose monomers (see Image. Glycogen, Free Glucose Release, and Glycogen Storage Diseases, Figure 1). After a meal, the plasma glucose level rises, stimulating the storage of the excess in cytoplasmic glycogen. The liver contains the highest percentage of glycogen by weight (about 10%), whereas muscles can store about 2% by weight. Nevertheless, since the total muscle mass is greater than the liver mass, the total mass of glycogen in muscles is about twice that of the liver. When needed, the glycogen polymer can be broken down into glucose monomers and utilized for energy production. Defects in the enzymes and transporters for these processes cause GSDs. An increasing number of GSDs are being identified, but most are very rare. These subtypes are classified numerically in the order of recognition and identification of the enzyme defect causing the disorder. Classification of Glycogen Storage Disorder GSDs that primarily affect the liver include the following: Glycogen synthase-2 deficiency (GSD type 0a). Glucose-6-phosphatase deficiency (GSD type Ia). Glucose-6-phosphate transporter deficiency (GSD type Ib) . Glycogen debrancher deficiency (GSD type III) . Glycogen branching enzyme deficiency (GSD type IV) . Liver phosphorylase deficiency (GSD type VI) . Phosphorylase kinase deficiency (GSD type IXa). GLUT2 deficiency or Fanconi-Bickel disease. GSDs that primarily affect the skeletal muscles include the following: Muscle phosphorylase deficiency (GSD type V). Phosphofructokinase deficiency (GSD type VII). Phosphoglycerate mutase deficiency (GSD type X). Lactate dehydrogenase A deficiency (GSD type XI) . Aldolase A deficiency (GSD type XII); β-enolase deficiency (GSD type XIII). Phosphoglucomutase-1 deficiency (GSD type XIV). GSDs that affect both skeletal and cardiac muscles include the following: Lysosomal acid maltase deficiency (GSD type IIa). Lysosome-associated membrane protein 2 deficiency (GSD type IIb). Glycogenin-1 deficiency (GSD type XV). Muscle glycogen synthase deficiency (GSD type 0b).

Glycogen Storage Disease Type VII (GSD VII) is a rare glycogen metabolism disorder resulting from mutations in the PFKM gene, inherited in an autosomal recessive manner. It is characterized by exercise intolerance, muscle cramps, myoglobinuria, compensatory hemolysis, and later onset de novo myasthenia and mild myopathy, contributing to its clinical heterogeneity and diagnostic challenges. Here, we report a rare case of a 17-year-old Chinese woman exhibiting substantial muscle weakness and compensated hemolysis. Muscle biopsies showed glycogen deposition, and blood tests showed hyperuricemia and significantly elevated creatine kinase. Whole genome sequencing (WGS) and whole exome sequencing (WES) identified two compound heterozygous mutations in the PFKM (NM_000289.6) gene: c.626G>A and c.1376G>A in exons 7 and 15, respectively. According to the clinical presentation, diagnostic examination, and WES results, the patient was finally diagnosed with GSDVII. The discovery of these two new PFKM mutations expands the genetic spectrum, and understanding the clinical manifestations of these mutations is critical to preventing diagnostic delays and timely intervention and treatment.