Reply to Leao-Teles et al

We appreciate the comments¹ on our review on autosomal recessive cutis laxa syndromes,² especially the novel information on the Portuguese patient CoFe³ (Table 1, Kornak et al), who was diagnosed with a combined N- and O-linked glycosylation disorder and ATP6V0A2-CDG. De Barsy syndrome is a challenging diagnosis, and has overlapping features with ARCL type 2, including cutis laxa, short stature, late closure of the fontanel, congenital hip dysplasia, some aspects of facial dysmorphism and psychomotor retardation.⁴ Still, dystonic movements and progressive corneal abnormalities are highly suggestive of De Barsy syndrome. So far no cobble-stone-like brain dysgenesis has been observed in De Barsy syndrome patients. Although the clinical differentiation is not always straightforward, progeroid features, the presence of pergamen-like skin and the absence of subcutaneous fat are distinctive.² Interestingly, some of the patients, recently reported to have PYCR1 mutations, were previously diagnosed with De Barsy syndrome,⁵ while other De Barsy patients were found to not harbour PYCR1 mutations (unreported data), thus supporting genetic heterogeneity. We would appreciate further description and photo documentation of this unique patient, reported by Leao-Teles, as in our own cohort of six patients with De Barsy syndrome and those studied by Kornak et al (personal communication) none of the children had either N-linked or O-linked glycosylation abnormalities, nor mutations in the ATP6V0A2 gene. Eye anomalies are common in N-glycosylation disorders,⁶ and strabismus and high myopia have been reported in combined glycosylation disorders.⁴ The exceptional observation of corneal abnormalities with a movement disorder in association with ATP6V0A2-CDG indeed widens the range of symptoms evoking glycosylation studies in patients with cutis laxa.