Ethylmalonic encephalopathy masquerading as meningococcemia

Cold Spring Harb Mol Case Stud. 2022 Mar 24;8(2):a006193. doi: 10.1101/mcs.a006193. Print 2022 Feb.


Ethylmalonic encephalopathy (MIM #602473) is a rare autosomal recessive metabolic condition caused by biallelic variants in ETHE1 (MIM #608451), characterized by global developmental delay, infantile hypotonia, seizures, and microvascular damage. The microvascular changes result in a pattern of relapsing spontaneous diffuse petechiae and purpura, positional acrocyanosis, and pedal edema, hemorrhagic suffusions of mucous membranes, and chronic diarrhea. Here, we describe an instructive case in which ethylmalonic encephalopathy masqueraded as meningococcal septicemia and shock. Ultrarapid whole-genome testing (time to result 60 h) and prompt biochemical analysis facilitated accurate diagnosis and counseling with rapid implementation of precision treatment for the metabolic crisis related to this condition. This case provides a timely reminder to consider rare genetic diagnoses when atypical features of more common conditions are present, with an early referral to ensure prompt biochemical and genomic diagnosis.

Keywords: acrocyanosis; ankle clonus; central hypotonia; cerebral ischemia; delayed fine motor development; delayed gross motor development; ethylmalonic aciduria; petechiae; progressive encephalopathy; recurrent cerebral hemorrhage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Diseases, Metabolic, Inborn
  • Humans
  • Mitochondrial Proteins / genetics
  • Nucleocytoplasmic Transport Proteins / genetics
  • Purpura* / diagnosis
  • Purpura* / genetics
  • Purpura* / metabolism
  • Sepsis*


  • ETHE1 protein, human
  • Mitochondrial Proteins
  • Nucleocytoplasmic Transport Proteins

Supplementary concepts

  • Ethylmalonic encephalopathy