Clinical and Laboratory ObservationsNeonatal diabetes mellitus, enteropathy, thrombocytopenia, and endocrinopathy: Further evidence for an X-linked lethal syndrome☆
Section snippets
Case Reports
Patient 1 was born prematurely. Hypotonia, ecchymoses, and an eczematous rash were noted at birth. He was unable to tolerate oral feeding because of apparent gut hypomotility, and jejunal atresia was suggested by findings on a barium swallow. Laparotomy on day 7 of life revealed a structurally normal but atonic gut. Ganglion cells were present in biopsy specimens at all levels, but there was complete loss of mucosa with a dense submucosal chronic inflammatory infiltrate.
Abnormal laboratory
Discussion
The affected males in the newly reported family had an inflammatory enteropathy manifesting as bowel hypomotility with a common histologic picture of mucosal erosion and a relatively primitive-appearing gut epithelium, endocrinopathy (hypothyroidism in 1, neonatal DM in 2, and parathyroid hormone resistance in 1), and thrombocytopenia and coagulopathy in 2. Patients 1 and 2 died at a few weeks of age, whereas patient 3, treated more expectantly, survived 5 months.
We believe these new cases
Acknowledgements
We thank Dr Raj Kapur for providing the pathologic description and illustration for case 2.
References (24)
- et al.
X-linked syndrome of polyendocrinopathy, immune dysfunction, and diarrhea maps to Xp11.23-Xq13.3
Am J Hum Genet
(2000) - et al.
An X-linked syndrome of diarrhea, polyendocrinopathy, and fatal infection in infancy
J Pediatr
(1982) - et al.
Congenital permanent diabetes mellitus and celiac disease
J Pediatr
(1982) - et al.
Diabete neonatal vrai associe a une maladie auto-immune
Arch Pediatr (Paris)
(1996) - et al.
The mouse homolog of the Wiskott-Aldrich syndrome protein (WASP) gene is highly conserved and maps near the scurfy (sf) mutation on the X chromosome
Genomics
(1995) - et al.
Long-term course of neonatal diabetes
N Engl J Med
(1995) - et al.
Manifestations and linkage analysis in X-linked autoimmunity-immunodeficiency syndrome
Am J Med Genet
(2000) - et al.
Apropos de deux cas de diabete neonatal
Ann Pediatr
(1970) - et al.
Congenital absence of the islets of Langerhans
Arch Dis Child
(1977) - et al.
Congenital diabetes mellitus and fatal secretory diarrhea in two infants
J Pediatr Gastroenterol Nutr
(1991)
A Japanese family of X-linked auto-immune enteropathy with haemolytic anemia and polyendocrinopathy
Eur J Pediatr
Hyperglycemies et diabetes neonatals
Arch Pediatr (Paris)
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Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A systematic review
2020, Autoimmunity ReviewsCitation Excerpt :This analysis does not include two recently reported cohorts of IPEX patients [82,83] published after completion of our manuscript Seventy-five articles that included a total of 195 patients affected by IPEX were identified [1–4,6,12–81] using our inclusion and exclusion criteria (Fig. 1) and their clinical presentation and individual FOXP3 mutations summarized in Supplementary Table 1. This analysis does not include two recently reported cohorts of IPEX patients [82,83] published after completion of our manuscript
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2016, Pediatric Allergy: Principles and Practice: Third EditionFetal-onset IPEX: Report of two families and review of literature
2015, Clinical ImmunologyCitation Excerpt :We deliberately did not consider cases informed as “neonatal onset”, since we would like to make sure that IPEX manifestations started in utero. Considering the FOXP3 mutations listed in Table 1, only the family reported by Levy-Lahad & Wildin (cases 1–3, Table 1) [6,17] and the family 1 here described (Fig. 1) bear the c.1189C > T mutation. Mutations detected in patients 4, 5, 6, 8, 10 and 11 (Table 1) were described only once in the literature.
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Reprint requests: Robert S. Wildin, MD, Department of Molecular and Medical Genetics, Oregon Health Sciences University, Mailcode L103A, 3181 SW Sam Jackson Park Rd, Portland, OR 97201-3098.