When neonatal inflammation does not mean infection: an early-onset mevalonate kinase deficiency with interstitial lung disease

Clin Immunol. 2019 Aug:205:25-28. doi: 10.1016/j.clim.2019.05.002. Epub 2019 May 13.

Abstract

Systemic inflammation in neonates is attributable to an infection in almost all cases. When inflammation persists, an autoinflammatory disease should be promptly suspected. We report here a case of mevalonate kinase deficiency (MKD) that presented at birth with mild symptoms and signs suggestive for a perinatal infection, together with the uncommon finding of interstitial lung disease. An extensive diagnostic work-up, performed after ineffective antibiotic treatment, demonstrated high levels of mevalonic acid in urine (7024 mM/M of creatinine, normal value <0.1). Next-generation sequencing showed a rare c.709A > T (p.T237S) homozygous mutation in the MVK gene, consistent with MKD. Treatment with anakinra led to a prompt resolution of symptoms and a sharp drop in serum inflammatory markers. The patient is now six months-old, currently undergoing evaluation for hematopoietic stem-cell transplantation. To our knowledge, this is the first case of MKD presenting within the first week of life with interstitial lung disease.

Keywords: Autoinflammatory disease; Hyper-IgD syndrome; IL-1β; Mevalonic aciduria; Neonatal infection; Periodic fever.

Publication types

  • Case Reports

MeSH terms

  • Diagnosis, Differential
  • Female
  • Humans
  • Infant, Newborn
  • Infections / diagnosis
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Lung Diseases, Interstitial / diagnosis*
  • Lung Diseases, Interstitial / drug therapy
  • Lung Diseases, Interstitial / etiology
  • Mevalonate Kinase Deficiency / complications
  • Mevalonate Kinase Deficiency / diagnosis*
  • Mevalonate Kinase Deficiency / drug therapy
  • Mevalonate Kinase Deficiency / genetics
  • Neonatal Sepsis / diagnosis*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Tomography, X-Ray Computed

Substances

  • Interleukin 1 Receptor Antagonist Protein
  • Phosphotransferases (Alcohol Group Acceptor)
  • mevalonate kinase