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Hyper IgM in tricho-hepato-enteric syndrome due to TTC37 mutation

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Tricho-hepato-enteric syndrome (THES) (OMIM #222,470) is a rare autosomal recessive syndromic enteropathy whose primary manifestations are dysmorphism, intractable diarrhea, failure to thrive, hair abnormalities, liver disease, and immunodeficiency with low serum IgG concentrations. THES is caused by mutations of either Tetratricopeptide Repeat Domain 37 (TTC37) or Ski2 like RNA Helicase (SKIV2L), genes that encode two components of the human SKI complex. Here, we report a patient with a TTC37 homozygous mutation phenotypically typical for tricho-hepato-enteric syndrome in whom extremely elevated IgM with low IgG was present at the time of diagnosis. These manifestations were not previously described in THES patients and this raised our index of suspicion towards “atypical” hyper IgM syndrome. Although the pathogenesis of immunoglobulin production dysfunction in THES is still elusive, this disorder should be considered in the differential diagnosis in patients with elevated IgM and syndromic features.

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The work of GS is supported in part by the Israel Ministry of Aliyah and Integration.

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All the authors contributed to the study conception and design. Material preparation, and data collection and analysis were performed by EK, AN, GL, GS, and AB. Genetic analysis was performed by MES, NH, OP, and OB. The first draft of the manuscript was written by EK and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Eyal Kristal.

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This study was approved by the institutional review board of Soroka University Medical Center.

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The authors declare no competing interests.

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Kristal, E., Nahum, A., Ling, G. et al. Hyper IgM in tricho-hepato-enteric syndrome due to TTC37 mutation. Immunol Res 70, 775–780 (2022).

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