Clinical Report: Identification of novel compound heterozygous variants in the MVK gene

Background

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive disorder characterized by mutations in the MVK gene, leading to a spectrum of clinical manifestations from mild hyper-IgD syndrome to severe mevalonic aciduria.

Data Highlights

Whole-exome sequencing identified two novel MVK variants: c.64G > A (p.Val22Met) and c.1063G > C (p.Ala355Pro), both absent in global population databases. The patient showed elevated urinary mevalonic acid and significant systemic inflammation.

Key Findings

• The patient presented with growth retardation, intractable diarrhea, recurrent fever, and hepatosplenomegaly.
• Laboratory tests indicated marked leukocytosis and elevated C-reactive protein levels.
• In silico analyses confirmed significant structural perturbations due to the identified MVK variants.
• The patient achieved sustained remission following treatment with canakinumab.
• This study expands the known mutational spectrum of MVK in East Asian populations.

Clinical Implications

The identification of novel MVK variants emphasizes the importance of genetic testing in diagnosing early-onset mevalonic aciduria.

Conclusion

This case highlights the critical role of genetic analysis in diagnosing severe autoinflammatory disorders.

Related Resources & Content

1. Frontiers in Endocrinology, 2026 -- Clinical and genotypic analysis of 79 children with methylmalonic acidemia: a retrospective single-center study in China
2. Frontiers in Pediatrics, 2026 -- Clinical phenotypes and genetic mutation analysis of 45 neonatal-onset methylmalonic acidemia
3. Frontiers in Pediatrics, 2026 -- Identification of Novel Compound Heterozygous Mutations in the GLB1 Gene by Whole-Exome Sequencing in a Case of Infantile GM1 Gangliosidosis: A Case Report
4. Myopathy and ataxia related to impaired mitochondrial function in mevalonate kinase deficiency | Orphanet Journal of Rare Diseases | Springer Nature Link
5. The 2021 EULAR/American College of Rheumatology Points to Consider for Diagnosis, Management and Monitoring of the Interleukin 1 Mediated Autoinflammatory Diseases
6. The Journal of Clinical Endocrinology & Metabolism — A Novel HADH Gene Mutation Linked to Congenital Hyperinsulinemic Hypoglycemia and Increased GLP-1 Receptor Expression in the Pancreas
7. Myopathy and ataxia related to impaired mitochondrial function in mevalonate kinase deficiency | Orphanet Journal of Rare Diseases | Springer Nature Link
8. The 2021 EULAR/American College of Rheumatology Points to Consider for Diagnosis, Management and Monitoring of the Interleukin 1 Mediated Autoinflammatory Diseases: Cryopyrin-Associated Periodic Syndromes, Tumour Necrosis Factor Receptor-Associated Periodic Syndrome, Mevalonate Kinase Deficiency, and Deficiency of the Intereukin-1 Receptor Antagonist - PMC
9. Systematic Review of Adverse Events of IL-1 and IL-6 Inhibitor Use in Pediatrics - PMC