Comment on: Eur J Hum Genet. 2009 Sep;17(9):1099-11

B Reversade

Dulce Quelhas

E Morava

EC Kivuva

Elisa Leao-Teles

J Jaeken

Jaak Jaeken

Laura Vilarinho

U Kornak

European Journal of Human Genetics

PubMed

Leao-Teles, Elisa

Quelhas, Dulce

Vilarinho, Laura

Scientific Repository of the National Health Institute Doutor Ricardo Jorge

De Barsy syndrome and ATP6V0A2-CDG

Repositório Científico do Instituto Nacional de Saúde

LETTERSDe Barsy syndrome andATP6V0A2-CDGEuropean Journal of Human Genetics (2010) 18, 526; doi:10.1038/ejhg.2009.218; published online 16 December 2009We read with interest the nice review of Morava et al1 on theautosomal recessive cutis laxa syndromes. The authors mention theDe Barsy syndrome and state that the genetic background of the DeBarsy syndrome has not yet been identified. However, in the paper byKornak et al2 on impaired glycosylation and cutis laxa caused bymutations in ATP6V0A2 (ATP6V0A2-CDG according to the novelnomenclature3,4), one of the patients (see patient CoFe in Table 1 ofKornak et al2) shows the full clinical picture of the De Barsy syndrome,including cutis laxa, facial dysmorphy, dwarfism, psychomotor retar-dation, dystonia, congenital hip dysplasia, and corneal dystrophynecessitating repeated corneal transplantation. These data suggestthat a subgroup of patients with De Barsy syndrome5 belongs to thespectrum of ATP6V0A2-CDG. Another cause of De Barsy syndromehas very recently been identified as mutations in PYCR1, coding fora mitochondrial enzyme involved in proline metabolism.6 Therefore,we recommend a systematic screen for ATP6V0A2-CDG and formutations in PYCR1 in patients with De Barsy syndrome.Elisa Leao-Teles1, Dulce Quelhas2, Laura Vilarinho2and Jaak Jaeken31Metabolic Unit, Department of Pediatrics, San Joao, Hospital,Porto, Portugal; 2Department of Clinical Biology, Institute of MedicalGenetics Jacinto de Magalha˜es, Porto, Portugal; 3Department ofPediatrics, Center for Metabolic Disease, University HospitalGasthuisberg, Leuven, BelgiumE-mail: jaak.jaeken@uzleuven.be1 Morava E, Guillard M, Lefeber DJ, Wevers RA: Autosomal recessive cutis laxa syndromerevisited. Eur J Hum Genet 2009; 17: 1099–1110.2 Kornak U, Reynders E, Dimopoulou A et al: Impaired glycosylation and cutis laxa caused bymutations in the vesicular H+-ATPase subunit ATP6V0A2. Nat Genet 2008; 40: 32–34.3 Jaeken J, Hennet T, Freeze HH, Matthijs G: On the nomenclature of congenital disordersof glycosylation (CDG). J Inherit Metab Dis 2008; 31: 669–672.4 Jaeken J, Hennet T, Matthijs G, Freeze HH: CDG nomenclature: time for a change.Biochim Biophys Acta 2009; 1792: 825–826.5 Kivuva EC, Parker MJ, Cohen MC, Wagner BE, Sobey G: De Barsy syndrome: a review ofthe phenotype. Clin Dysmorphol 2008; 17: 99–107.6 Reversade B, Escande Beillard N, Dimopoulou A et al: Mutations in PYCR1 cause cutislaxa with progeroid features. Nat Genet 2009; 41: 1016–1021.Reply to Leao-Teles et alEuropean Journal of Human Genetics (2010) 18, 526; doi:10.1038/ejhg.2009.219; published online 16 December 2009We appreciate the comments1 on our review on autosomal recessivecutis laxa syndromes,2 especially the novel information on thePortuguese patient CoFe3 (Table 1, Kornak et al), who was diagnosedwith a combined N- and O-linked glycosylation disorder andATP6V0A2-CDG. De Barsy syndrome is a challenging diagnosis,and has overlapping features with ARCL type 2, including cutislaxa, short stature, late closure of the fontanel, congenital hipdysplasia, some aspects of facial dysmorphism and psychomotorretardation.4 Still, dystonic movements and progressive cornealabnormalities are highly suggestive of De Barsy syndrome. So far nocobble-stone-like brain dysgenesis has been observed in De Barsysyndrome patients. Although the clinical differentiation is not alwaysstraightforward, progeroid features, the presence of pergamen-likeskin and the absence of subcutaneous fat are distinctive.2 Interestingly,some of the patients, recently reported to have PYCR1mutations, werepreviously diagnosed with De Barsy syndrome,5 while other De Barsypatients were found to not harbour PYCR1 mutations (unreporteddata), thus supporting genetic heterogeneity. We would appreciatefurther description and photo documentation of this unique patient,reported by Leao-Teles, as in our own cohort of six patients with DeBarsy syndrome and those studied by Kornak et al (personalcommunication) none of the children had either N-linked orO-linked glycosylation abnormalities, nor mutations in the ATP6V0A2gene. Eye anomalies are common in N-glycosylation disorders,6 andstrabismus and high myopia have been reported in combined glyco-sylation disorders.4 The exceptional observation of corneal abnorm-alities with a movement disorder in association with ATP6V0A2-CDGindeed widens the range of symptoms evoking glycosylation studies inpatients with cutis laxa.CONFLICT OF INTERESTThe authors declare no conflict of interest.Eva Morava1, Maı¨lys Guillard2, Dirk J Lefeber2and Ron AWevers21Department of Paediatrics, Radboud University Nijmegen MedicalCentre, Nijmegen, The Netherlands;2Laboratory of Paediatrics and Neurology, Radboud University NijmegenMedical Centre, Nijmegen, The NetherlandsE-mail: E.Morava@cukz.umcn.nl1 Leao-Teles E, Quelhas D, Vilarinho L, Jaeken J: De Barsy syndrome and ATP6V0A2-CDG.Eur J Human Genet 2010; 18: 526.2 Morava E, Guillard M, Lefeber DJ, Wevers RA: Autosomal recessive cutis laxa syndromerevisited. Eur J Hum Genet 2009; 17: 1099–1110.3 Kornak U, Reynders E, Dimopoulou A et al: Impaired glycosylation and cutis laxacaused by mutations in the vesicular H+-ATPase subunit ATP6V0A2. Nat Genet 2008;40: 32–34.4 Hucthagowder V, Morava E, Kornak U et al: Loss-of-function mutations in ATP6V0A2impair vesicular trafficking, tropoelastin secretion and cell survival. Hum Mol Genet2009; 18: 2149–2165.5 Reversade B, Escande-Beillard N, Dimopoulou A et al: Mutations in PYCR1 cause cutislaxa with progeroid features. Nat Genet 2009; 41: 1016–1021.6 Morava E, Wosik HN, Sykut-Cegielska J et al: Ophthalmological abnormalitiesin children with congenital disorders of glycosylation type I. Br J Ophthalmol 2009;93: 350–354.European Journal of Human Genetics (2010) 18, 526& 2010 Macmillan Publishers Limited All rights reserved 1018-4813/10 $32.00www.nature.com/ejhg

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De Barsy syndrome and ATP6V0A2-CDG

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