Congenital Myasthenic Syndrome Associated With SLC25A1 Gene Variant: The First Reported Case in Saudi Arabia

Area of Science:

• Genetics
• Neurology
• Biochemistry

Background:

• Congenital myasthenic syndrome (CMS) is a group of neuromuscular junction disorders.
• Autosomal recessive combined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA) is a rare metabolic disorder.

Observation:

• A two-year-old girl presented with hypotonia, ptosis, apnea, and global developmental delay.
• Whole exome sequencing identified a homozygous variant in the SLC25A1 gene, consistent with D/L-2-HGA.
• Clinical presentation and genetic findings suggested a diagnosis of CMS type 23.

Findings:

• The patient was diagnosed with autosomal recessive combined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA).
• Genetic analysis revealed a likely pathogenic homozygous variant c.842C>T p.(Ala281Val) in the SLC25A1 gene.
• The diagnosis of congenital myasthenic syndrome (CMS) type 23 was supported by genetic results.

Implications:

• Early diagnosis and treatment with pyridostigmine led to substantial clinical improvement.
• This case underscores the genetic heterogeneity of CMS and the importance of comprehensive genetic testing.
• The study highlights the potential overlap between metabolic and neuromuscular disorders.