Ultraschall Med 2023; 44(S 01): S15
DOI: 10.1055/s-0043-1772289
Abstracts
Gynäkologie & Geburtshilfe
Vorträge

A causal treatment for X-linked Hypohidrotic Ectodermal Dysplasia: Long-term results of short-term protein replacement in utero

Holm Schneider
1   Universitätskinderklinik Erlangen, Germany
2   Zentrum für Ektodermale Dysplasien
,
Christine Schweikl
1   Universitätskinderklinik Erlangen, Germany
2   Zentrum für Ektodermale Dysplasien
,
Smail Hadj-Rabia
3   Department of Dermatology and Reference Center for Rare Skin Diseases (MAGEC); Université de Paris-Centre, Hôpital Necker – Enfants malades, France
,
Matthias Beckmann
4   Universitätsfrauenklinik Erlangen, Germany
,
Pascal Schneider
5   Department of Biochemistry, University of Lausanne
,
Florian Faschingbauer
4   Universitätsfrauenklinik Erlangen, Germany
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A causal treatment for X-linked hypohidrotic ectodermal dysplasia: Long-term results of short-term protein replacement in utero

Background X-linked hypohidrotic ectodermal dysplasia (XLHED), caused by genetic deficiency of ectodysplasin A1 (EDA1), is a rare developmental disorder of ectodermal derivatives, such as hair, sweat glands, and teeth. The absence of sweat glands and perspiration can evoke life-threatening hyperthermia. Fetal tooth germ sonography is highly reliable in detecting XLHED prenatally.

Patients and Methods We have treated 6 male fetuses with obvious signs of XLHED by ultrasound-guided intra-amniotic administration of a recombinant EDA1 replacement protein, Fc-EDA, in gestational week 26 and beyond. Follow-up examinations were performed for up to 6 years [1] [2] [3].

Results Prenatal EDA1 replacement resulted in ample sweat gland development and pilocarpine-inducible sweating in all treated subjects, who have also got more permanent teeth than their untreated affected relatives. In the two oldest boys treated repeatedly with Fc-EDA in utero, normal perspiration has been persisting for 6 years. Lower sweat production after single prenatal dosing may indicate a dose-response relationship.

Conclusion A causal treatment of XLHED before birth is feasible. Routine fetal tooth assessment could identify candidates for the current genotype-match controlled multicentre study to investigate the efficacy and safety of intra-amniotic Fc-EDA administration to male subjects with XLHED.


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  • References

  • 1 Schneider H., Faschingbauer F.. et al. Prenatal correction of X-linked hypohidrotic ectodermal dysplasia. N. Engl. J. Med. 2018; 378: 1604-1610
    CrossrefPubMedSearch in Google Scholar
  • 2 Körber I.. et al. Safety and immunogenicity of Fc-EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects. Br. J. Clin. Pharmacol. 2020; 86: 2063-2069
    CrossrefPubMedSearch in Google Scholar
  • 3 Schneider H., Hadj-Rabia S.. et al. Protocol for the phase 2 EDELIFE trial investigating the efficacy and safety of intra-amniotic ER004 administration to male subjects with X-linked hypohidrotic ectodermal dysplasia. Genes 2023; 14: 153
    CrossrefPubMedSearch in Google Scholar

Publication History

Article published online:
29 August 2023

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  • References

  • 1 Schneider H., Faschingbauer F.. et al. Prenatal correction of X-linked hypohidrotic ectodermal dysplasia. N. Engl. J. Med. 2018; 378: 1604-1610
    CrossrefPubMedSearch in Google Scholar
  • 2 Körber I.. et al. Safety and immunogenicity of Fc-EDA, a recombinant ectodysplasin A1 replacement protein, in human subjects. Br. J. Clin. Pharmacol. 2020; 86: 2063-2069
    CrossrefPubMedSearch in Google Scholar
  • 3 Schneider H., Hadj-Rabia S.. et al. Protocol for the phase 2 EDELIFE trial investigating the efficacy and safety of intra-amniotic ER004 administration to male subjects with X-linked hypohidrotic ectodermal dysplasia. Genes 2023; 14: 153
    CrossrefPubMedSearch in Google Scholar