Isolated neurological presentations of mevalonate kinase deficiency

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Mevalonate kinase (MK) deficiency is a rare autosomal recessive metabolic disorder.
• Pathogenic variants in the *MVK* gene cause MK deficiency, leading to a spectrum of symptoms.
• Neurological symptoms are typically observed alongside autoinflammatory features in severe cases.

Observation:

• This study describes a patient with MK deficiency presenting severe neurological symptoms but lacking autoinflammation.
• Similar cases were identified in existing literature, suggesting a non-inflammatory phenotype.
• A specific genotype, *MVK* p.(His20Pro)/p.(Ala334Thr), may be associated with this non-inflammatory presentation.

Findings:

• The non-inflammatory phenotype of MK deficiency may be underdiagnosed.
• Clinicians might overlook MK deficiency in patients with only neurological symptoms, such as psychomotor delay and ataxia.
• Neurological manifestations of MK deficiency without hyperinflammation could be more prevalent than previously thought.

Implications:

• Consider MK deficiency in patients with psychomotor delay and ataxia, irrespective of inflammatory symptoms.
• This highlights the importance of genetic testing for *MVK* gene variants in unexplained neurological disorders.
• Further research is needed to fully understand the genotype-phenotype correlations in MK deficiency.