Deciphering the genetic link between familial hypobetalipoproteinemia and neuromuscular disorder: a case report

We present a case of a white 21-year-old male patient who showed symptoms of both Familial hypobetalipoproteinemia and neuromuscular abnormalities linked to a mutation (c.7564C > T) in the APOB gene in addition to several other mutations identified that are potentially related to neuromuscular disorders. Familial hypobetalipoproteinemia is characterized by low levels of lipids in the blood due to genetic mutations affecting lipoprotein pathways, including the APOB gene. Although muscular atrophy symptoms are less commonly associated with APOB mutations, they were observed in this case. This report emphasizes the importance of recognizing the potential overlap of these two different disorders and other mutations we see in our patients and provides valuable information for clinicians who may encounter similar cases.

A 21-year-old white male presented to his primary care clinic with a chief complaint of a one-year history of progressive muscle weakness, primarily affecting the upper extremities. He reported difficulty completing pushups and performing other physical tasks required by his military duties. He had no psychosocial history available, no known allergies, was not taking any medications, and denied any family history of neuromuscular disease. The patient maintained a rigorous physical training regimen, which helped bring his symptoms to attention.

This case represents a first unique instance of multiple genetic mutations coinciding with a distinct neuromuscular presentation rather than a proven direct link between APOB mutation and neuromuscular disorders. It identified a truncating APOB variant associated with FHBL and several variants of uncertain significance in muscle-related genes. The findings suggest a possible link between disorders of lipid metabolism and secondary muscular impairment, potentially mediated by factors such as lipid accumulation, oxidative stress, and muscle tissue damage. These observations contribute to medical understanding and underscore the complex nature of genetic contributions to neuromuscular disorders and reinforce the importance of a multidisciplinary approach in evaluating patients with unexplained muscle weakness and abnormal lipid metabolism.