Document Detail

Rapid degradation of an active formylglycine generating enzyme variant leads to a late infantile severe form of multiple sulfatase deficiency.
MedLine Citation:
PMID:  23321616     Owner:  NLM     Status:  MEDLINE    
Multiple sulfatase deficiency (MSD) is a rare inborn error of metabolism affecting posttranslational activation of sulfatases by the formylglycine generating enzyme (FGE). Due to mutations in the encoding SUMF1 gene, FGE's catalytic capacity is impaired resulting in reduced cellular sulfatase activities. Both, FGE protein stability and residual activity determine disease severity and have previously been correlated with the clinical MSD phenotype. Here, we report a patient with a late infantile severe course of disease. The patient is compound heterozygous for two so far undescribed SUMF1 mutations, c.156delC (p.C52fsX57) and c.390A>T (p.E130D). In patient fibroblasts, mRNA of the frameshift allele is undetectable. In contrast, the allele encoding FGE-E130D is expressed. FGE-E130D correctly localizes to the endoplasmic reticulum and has a very high residual molecular activity in vitro (55% of wildtype FGE); however, it is rapidly degraded. Thus, despite substantial residual enzyme activity, protein instability determines disease severity, which highlights that potential MSD treatment approaches should target protein folding and stabilization mechanisms.
Lars Schlotawa; Karthikeyan Radhakrishnan; Matthias Baumgartner; Regula Schmid; Bernhard Schmidt; Thomas Dierks; Jutta Gärtner
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-16
Journal Detail:
Title:  European journal of human genetics : EJHG     Volume:  21     ISSN:  1476-5438     ISO Abbreviation:  Eur. J. Hum. Genet.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-08-16     Completed Date:  2014-03-24     Revised Date:  2014-09-02    
Medline Journal Info:
Nlm Unique ID:  9302235     Medline TA:  Eur J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  1020-3     Citation Subset:  IM    
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MeSH Terms
Cell Line, Tumor
Child, Preschool
Enzyme Stability / genetics
Fatal Outcome
Molecular Diagnostic Techniques
Multiple Sulfatase Deficiency Disease / diagnosis*,  genetics,  pathology
Sulfatases / genetics*,  metabolism
Reg. No./Substance:
EC 3.1.6.-/SUMF1 protein, human; EC 3.1.6.-/Sulfatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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