Fulminant Necrotizing Enterocolitis and Multiple Organ Dysfunction in a Toddler with Mitochondrial DNA Depletion Syndrome-13

Abstract

Necrotizing enterocolitis (NEC) is exceptional after the neonatal period. A toddler with encephalopathy, mitochondrial myopathy, and hypertrophic cardiomyopathy developed fatal NEC and multiple organ dysfunction within 48 hours of the introduction of enteral feeding. She was subsequently found to have pathogenic mutations in FBXL4, a cause of mitochondrial DNA depletion syndrome-13. Intestinal dysmotility in the context of deficient mitochondrial respiration may have contributed to the development of NEC. Current paradigms call for early introduction of enteral nutrition to reinstate energy homeostasis. Enteral feeding should be administered with caution during metabolic crises of patients with mitochondrial DNA depletion syndromes.

Keywords

necrotizing enterocolitis - mitochondrial DNA depletion syndrome - FBXL4 - multiple organ dysfunction syndrome

• References

• 1 Jouvet P, Touati G, Lesage F. , et al. Impact of inborn errors of metabolism on admission and mortality in a pediatric intensive care unit. Eur J Pediatr 2007; 166 (05) 461-465
• 2 El-Hattab AW, Dai H, Almannai M. , et al. Molecular and clinical spectra of FBXL4 deficiency. Hum Mutat 2017; 38 (12) 1649-1659
• 3 El-Hattab AW, Craigen WJ, Scaglia F. Mitochondrial DNA maintenance defects. Biochim Biophys Acta Mol Basis Dis 2017; 1863 (06) 1539-1555
• 4 Gai X, Ghezzi D, Johnson MA. , et al. Mutations in FBXL4, encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy. Am J Hum Genet 2013; 93 (03) 482-495
• 5 Bonnen PE, Yarham JW, Besse A. , et al. Mutations in FBXL4 cause mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance. Am J Hum Genet 2013; 93 (03) 471-481
• 6 Giordano C, Sebastiani M, De Giorgio R. , et al. Gastrointestinal dysmotility in mitochondrial neurogastrointestinal encephalomyopathy is caused by mitochondrial DNA depletion. Am J Pathol 2008; 173 (04) 1120-1128
• 7 Finsterer J, Frank M. Gastrointestinal manifestations of mitochondrial disorders: a systematic review. Therap Adv Gastroenterol 2017; 10 (01) 142-154
• 8 Mehta NM, Skillman HE, Irving SY. , et al. Guidelines for the provision and assessment of nutrition support therapy in the pediatric critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. Pediatr Crit Care Med 2017; 18 (07) 675-715
• 9 Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D. ; CARE Group*. The CARE guidelines: consensus-based clinical case reporting guideline development. Glob Adv Health Med 2013; 2 (05) 38-43
• 10 Neu J, Walker WA. Necrotizing enterocolitis. N Engl J Med 2011; 364 (03) 255-264
• 11 Ballance WA, Dahms BB, Shenker N, Kliegman RM. Pathology of neonatal necrotizing enterocolitis: a ten-year experience. J Pediatr 1990; 117 (1 Pt 2): S6-S13
• 12 Viscomi C, Zeviani M. MtDNA-maintenance defects: syndromes and genes. J Inherit Metab Dis 2017; 40 (04) 587-599
• 13 Ho MS, Tsai PI, Chien CT. F-box proteins: the key to protein degradation. J Biomed Sci 2006; 13 (02) 181-191
• 14 Huemer M, Karall D, Schossig A. , et al. Clinical, morphological, biochemical, imaging and outcome parameters in 21 individuals with mitochondrial maintenance defect related to FBXL4 mutations. J Inherit Metab Dis 2015; 38 (05) 905-914
• 15 Ebrahimi-Fakhari D, Seitz A, Kölker S, Hoffmann GF. Recurrent stroke-like episodes in FBXL4-associated early-onset mitochondrial encephalomyopathy. Pediatr Neurol 2015; 53 (06) 549-550
• 16 Almannai M, Dai H, El AW, Wong L-JC. FBXL4-related encephalomyopathic mitochondrial DNA depletion syndrome. In: Adam MP AH, Pagon RA. , et al, eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 2017: 15
• 17 Li QY, An Y, Liu L. , et al. Differences in the clinical characteristics of early- and late-onset necrotizing enterocolitis in full-term infants: a retrospective case-control Study. Sci Rep 2017; 7: 43042
• 18 Ostlie DJ, Spilde TL, St Peter SD. , et al. Necrotizing enterocolitis in full-term infants. J Pediatr Surg 2003; 38 (07) 1039-1042
• 19 Diekman EF, Boelen CC, Prinsen BH. , et al. Necrotizing enterocolitis and respiratory distress syndrome as first clinical presentation of mitochondrial trifunctional protein deficiency. JIMD Rep 2013; 7: 1-6
• 20 Ackland G, Grocott MP, Mythen MG. Understanding gastrointestinal perfusion in critical care: so near, and yet so far. Crit Care 2000; 4 (05) 269-281
• 21 Guzman JA, Kruse JA. Splanchnic hemodynamics and gut mucosal-arterial PCO(2) gradient during systemic hypocapnia. J Appl Physiol (1985) 1999; 87 (03) 1102-1106
• 22 Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell 2005; 120 (04) 483-495
• 23 Jain IH, Zazzeron L, Goli R. , et al. Hypoxia as a therapy for mitochondrial disease. Science 2016; 352 (6281): 54-61