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Case Reports
. 2022 Dec;43(12):1829-1836.
doi: 10.1002/humu.24437. Epub 2022 Jul 23.

Clinical and pathophysiological delineation of musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE): A detailed and comprehensive glycobiological and pathological investigation in a novel patient

Mari Minatogawa  1   2 , Takuya Hirose  3 , Shuji Mizumoto  4 , Tomomi Yamaguchi  1   2   5 , Chiai Nagae  6 , Masashi Taki  7 , Shuhei Yamada  4 , Takafumi Watanabe  3 , Tomoki Kosho  1   2   5   8
Affiliations
Case Reports

Clinical and pathophysiological delineation of musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE): A detailed and comprehensive glycobiological and pathological investigation in a novel patient

Mari Minatogawa et al. Hum Mutat. 2022 Dec.

Abstract

Musculocontractural Ehlers-Danlos syndrome caused by dermatan sulfate epimerase deficiency (mcEDS-DSE) is a rare connective tissue disorder. This is the first report describing the detailed and comprehensive clinical and pathophysiological features of mcEDS-DSE. The patient, with a novel homozygous nonsense variant (NM_013352.4:c.2601C>A:p.(Tyr867*)), exhibited mild skin hyperextensibility without fragility and small joint hypermobility, but developed recurrent large subcutaneous hematomas. Dermatan sulfate (DS) moieties on chondroitin sulfate/DS proteoglycans were significantly decreased, but remained present, in skin fibroblasts. Electron microscopy examination of skin specimens, including cupromeronic blue-staining to visualize glycosaminoglycan (GAG) chains, revealed coexistence of normally assembled collagen fibrils with attached curved GAG chains and dispersed collagen fibrils with linear GAG chains from attached collagen fibrils across interfibrillar spaces to adjacent fibrils. Residual activity of DS-epi1, encoded by DSE, and/or compensation by DS-epi2, a minor homolog of DS-epi1, may contribute to the mild skin involvement through this "mosaic" pattern of collagen fibril assembly.

Keywords: cupromeronic blue-staining; dermatan sulfate; dermatan sulfate epimerase; musculocontractural Ehlers-Danlos syndrome; skin ultrastructure.

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References

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