title: Severe early-onset colitis revealing mevalonate kinase deficiency.
abstract: Hyperimmunoglobulinemia D is the less severe form of mevalonate kinase deficiency (MKD) caused by recessive inherited mutation in the mevalonate kinase gene. Hyperimmunoglobulinemia D is characterized by febrile attacks, often associated with transient digestive manifestations, such as abdominal pain, diarrhea, and vomiting. Here we report for the first time 2 patients with MKD revealed by severe neonatal colitis. Both patients had chronic bloody diarrhea and failure to thrive; 1 patient since the age of 1 month and the other since the age of 12 days. Total parenteral nutrition was required. A marked elevation of acute phase reactants was present, and no evidence of infection was found. In patient 1, ileocolonoscopy revealed ulcerative colitis at the age of 5 months. Patient 2 suffered from enterocolitis and shock, associated with multiple bowel adhesions at age 5 weeks; the rectosigmoidoscopy showed aphtoid lesions of the sigmoid colon. Pathologic findings of colonic biopsies revealed a dense polymorph inflammatory infiltrate associated with deep ulcerations. Febrile attacks occurred 2 months after the onset of digestive symptoms in patient 1, and at onset of disease in patient 2. Genomic sequencing of the mevalonate kinase gene revealed compound heterozygous mutations in both patients. Anti-interleukin-1 agent produced long-term remission of all digestive features and laboratory parameters. This report emphasizes that MKD may be the cause of severe early-onset inflammatory colitis, and must be considered by physicians, even in the absence of fever, after ruling out infections. Anti-interleukin-1 therapy may result in a dramatic improvement of MKD-related inflammatory bowel disease.
authors: Departments of Pediatric Gastroenterology, Assistance Publique-Hôpitaux de Paris, Robert Debré Hospital and University, Paris 19, Paris, France.
authors: Michael
authors: M
authors: Levy
authors: Alina
authors: A
authors: Arion
authors: Dominique
authors: D
authors: Berrebi
authors: Laurence
authors: L
authors: Cuisset
authors: Corinne
authors: C
authors: Jeanne-Pasquier
authors: Brigitte
authors: B
authors: Bader-Meunier
authors: Camille
authors: C
authors: Jung
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000209:etiology* / Q000235:genetics; D003113:Colonoscopy; D004252:DNA Mutational Analysis; D003968:Diarrhea, Infantile / Q000209:etiology; D004760:Enterocolitis / Q000175:diagnosis* / Q000209:etiology* / Q000235:genetics; D005183:Failure to Thrive / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D010289:Parenteral Nutrition, Total; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase
keywords: Mevalonate kinase deficiency; anti-interleukin-1; colitis; infant