Mutations in GMPPB Presenting with Pseudometabolic Myopathy

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Mutations in the guanosine diphosphate mannose (GDP-mannose) pyrophosphorylase B (GMPPB) gene are linked to congenital (CMD) and limb girdle muscular dystrophy (LGMD).
• These mutations affect the glycosylation pathway, leading to reduced alpha-dystroglycan (α-DG) in muscle biopsies.
• Clinical presentations vary widely, from severe CMD to milder LGMD, sometimes with intellectual disability and epilepsy.

Purpose of the Study:

• To investigate the genetic basis of a patient with a suspected metabolic myopathy and reduced α-DG.
• To expand the understanding of the phenotypic spectrum associated with GMPPB gene mutations.

Main Methods:

• Genetic analysis to identify mutations in the GMPPB gene.
• Biochemical assays to assess α-DG glycosylation levels.
• Clinical evaluation including muscle biopsy and creatine kinase (CK) level assessment.

Main Results:

• Two missense mutations in the GMPPB gene were identified in a 21-year-old male patient.
• The patient presented with elevated CK levels, myalgia, exercise intolerance, and myoglobinuria, mimicking metabolic myopathy.
• Muscle biopsy revealed minimal changes, but a significant reduction in glycosylated α-DG was observed.

Conclusions:

• This case broadens the known clinical and molecular spectrum of GMPPB-related disorders.
• Highlights the importance of molecular genetic testing and assessing α-DG glycosylation in patients with unexplained myopathies.