Exploring Secondary Biotinidase Deficiency and Biotin Supplementation in PMM2-CDG

Nastassja Himmelreich; Sven F. Garbade; Jürgen G. Okun; Simone Hengst; Virginia Geiger; Rita Barone; Saskia B. Wortmann; Christian Thiel

doi:10.1055/a-2708-3016

Neuropediatrics, Inhaltsverzeichnis

Neuropediatrics
DOI: 10.1055/a-2708-3016

Original Article

Exploring Secondary Biotinidase Deficiency and Biotin Supplementation in PMM2-CDG

Authors

Nastassja Himmelreich

¹Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany
Sven F. Garbade

¹Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany
Jürgen G. Okun

¹Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany
Simone Hengst

¹Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany
Virginia Geiger

¹Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany
Rita Barone

²Child Neuropsychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

³Research Unit of Rare Diseases and Neurodevelopmental Disorders, Oasi Research Institute-IRCCS, Troina, Italy
Saskia B. Wortmann

⁴University Children's Hospital, Paracelsus Medical University (PMU), Salzburg, Austria

⁵Integriertes Sozialpädiatrisches Zentrum (iSPZ), Munich, Germany
Christian Thiel

¹Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany

Abstract

Background

The congenital disorders of glycosylation (CDG) encompass >190 multiorgan disorders with predominantly neurodevelopmental phenotypes with no causative treatment available. The glycoprotein biotinidase (BTD) provides biotin, an essential cofactor for carboxylases in ubiquitous metabolic pathways. Individuals with (partial) BTD deficiency (BTDD) and CDG patients show overlapping phenotypes like movement disorders, seizures, and neurodevelopmental issues. Biotin is a water-soluble, inexpensive, and safe food supplement. Patients with primary BTDD respond well to oral biotin supplement. We here explore secondary BTDD and the effect of biotin supplementation in PMM2-CDG in an initial open-label study.

Methods

BTD activity in dried blood spots from 29 individuals with PMM2-CDG indicated a mean reduction to 27% (range: 23.0–40.5%) at group level. Patients (mean: 19.6 ± 11.9 years) were supplemented with 10 mg biotin daily for 12 months. The parents/caretaker reported positive responses in 62 to 69% of patients across seven (performance, social, at home, self-control, self-care, leisure, health) of the nine categories covered by the Adaptive Behavior Assessment System-II (ABAS-II) questionnaires. The reported positive effect of biotin supplementation differed between age groups, ranging from 54% (16–43 years) via 62% (2–5 years) to 80% (6–13 years). Its effect was reported to be the highest in the moderate to severely affected patient subgroups, with significant improvements in home functioning, health, performance, leisure, self-control. No adverse effects were reported.

Conclusion

Given the absence of other treatments, the supportive effect of Biotin in PMM2-CDG deserves further exploration.

Keywords

congenital disorders of glycosylation - therapy - vitamin H - biotinidase deficiency - treatment - seizures - movement disorder - rare disease

Volltext

Referenzen

References
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