The Persistent Generalized Muscle Contraction in Siblings with Molybdenum Cofactor Deficiency Type A

Area of Science:

• Biochemistry
• Genetics
• Neurology

Background:

• Molybdenum cofactor deficiency (MoCD) is a rare, severe metabolic disorder.
• MoCD type A (MoCD-A) is caused by mutations in the MOCS1 gene and typically presents with significant neurological impairment.
• Long-term neurological data for MoCD-A patients are scarce due to limited survival rates.

Observation:

• Two adult female siblings with MoCD-A, aged 26 and 22, were studied.
• Clinical presentation included feeding difficulties, neurological decline, and generalized muscle contractions mimicking status dystonicus.
• Distinctive brain MRI findings showed abnormalities in basal ganglia and cerebral white matter, sparing the thalamus.

Findings:

• Biochemical analyses revealed low serum uric acid and elevated urinary sulfocysteine and xanthine.
• Genetic analysis identified a novel homozygous MOCS1 variant (c.949C>T p.Arg317Cys) in both siblings.
• The identified MOCS1 variant was confirmed as pathogenic through biochemical correlation.

Implications:

• MoCD should be considered in the differential diagnosis for persistent generalized muscle contractions and specific MRI abnormalities.
• This study expands the understanding of long-term neurological manifestations in MoCD-A.
• The findings highlight the importance of genetic and biochemical testing for diagnosing MoCD.