To report a case of a 7-month-old Chinese infant with severe neonatal-onset mevalonic aciduria (MA) caused by novel compound heterozygous variants in the MVK gene, highlighting the importance of genetic testing.
Approach:
Clinical Presentation: The infant exhibited growth retardation, intractable diarrhea, recurrent fever, generalized rash, progressive hepatosplenomegaly, and persistent systemic inflammation.
Genetic Analysis: Whole-exome sequencing identified two novel compound heterozygous MVK variants: c.64G > A (p.Val22Met) and c.1063G > C (p.Ala355Pro), absent in global population databases.
In Silico Analysis: Structural modeling and pathogenicity prediction confirmed significant structural perturbations due to the identified variants.
Treatment: The patient achieved sustained remission with canakinumab.
Key Findings:
The patient had two novel compound heterozygous variants in the MVK gene.
Both variants were confirmed to cause severe functional impairment, contributing to the clinical presentation of MA.
This case expands the mutational spectrum of MKD in Chinese populations, providing insights into genetic diversity.
Interpretation:
The findings enhance understanding of genotype-phenotype correlations in severe MA, supporting the need for early differential diagnosis of neonatal autoinflammatory disorders.
Limitations:
The study is based on a single case report, limiting generalizability to broader populations.
Further studies are needed to assess the prevalence and clinical significance of these variants in diverse populations.
Conclusion:
This study highlights the importance of genetic testing in diagnosing early-onset mevalonic aciduria and contributes to the understanding of MKD in East Asian populations.
