Phosphoglycerate kinase deficiency: A nationwide multicenter retrospective study

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Phosphoglycerate kinase (PGK) deficiency is a rare X-linked metabolic disorder.
• It is caused by mutations in the PGK1 gene and typically presents with hemolytic anemia, myopathy, or central nervous system disorders.

Observation:

• A national multicenter retrospective study identified three unrelated French patients with PGK deficiency.
• Case 1 presented with sensorimotor polyneuropathy resembling Charcot-Marie-Tooth (CMT) disease.
• Case 2 experienced exertional rhabdomyolysis, and Case 3 had nonspherocytic hemolytic anemia (NSHA) with neurological and visual impairments.

Findings:

• The study identified new PGK1 gene mutations (c.323G>A, c.943G>A, c.491A>T) in the affected patients.
• PGK deficiency exhibits a broad phenotypic spectrum, including previously unrecognized peripheral nervous system involvement.
• This is the first report of PGK deficiency presenting as a CMT-like disorder.

Implications:

• PGK deficiency should be considered in the differential diagnosis of unexplained peripheral neuropathies, particularly CMT.
• Further research is warranted to elucidate the mechanisms linking PGK deficiency to neurological manifestations.
• Understanding the full spectrum of PGK deficiency can improve diagnostic accuracy and patient management.