diagnosis; symptoms/signs present on first referral to hospital and atdiagnosis; time between first referral and diagnosis; specialtiesconsulted for symptoms/signs attributable to storage disorder beforediagnosis was made; specialty making the diagnosis and treatmentreceived. Median age of all cases at diagnosis was 16 months (range9.5 months-15 yrs 3 months). Time to diagnosis ranged from 0months (prenatal diagnosis) to 11 years (alpha mannosidosis).Median time to diagnosis in severe MPS I was 9 months. All casesof MPS II and MPS I (attenuated form) had a time to diagnosisexceeding 3 years 10 months. Most diagnoses were made by aspecialist metabolic team (10/19 cases). The most frequent present-ing features were hernia (6/19 cases), lumbar kyphosis (5/19 cases)and hearing loss (3/19 cases) Delay to diagnosis was common,echoing data from international MPS registries. Knowledge ofcommon presenting features will allow for targeted education toaid early recognition of children with MPS particularly to rheuma-tology and orthopaedics.

doi:10.1016/j.ymgme.2013.12.090

79Psychological distress in children when lysosomal disease impairscommunication: what parents and professionals report

Delphine Genevaza, Alessia Perifanoa, Régine Scellesb, aVaincre lesMaladies Lysosomales Organisation (VML), Massy, France, bRouen Univer-sity, Rouen, France

During discussionswith families participating in “Vaincre lesMaladiesLysosomales” (VML, the French non-profit organisation of patients andtheir families), it is regularly reported that children with lysosomaldisease experience periods of depression. When these periods ofdepression are reported to physicians, they are usually diagnosed asprogression of the disease and not as a psychological problem.Paradoxically, during the past few years, there has been an increase inantidepressant prescriptions for these children. In most cases, lysosomaldiseases lead to severe disabilities, with large variability in the type andthe severity of lesions including cognitive impairments. For childrenwhose ability to communicate has been damaged, how can psychologicalsuffering be identified, in distinction from physical pain? How is itexpressed? VML therefore decided to conduct preliminary research toidentify the signs of possible mental suffering. Methodologically, thisstudy required access to the subjective experience of these childrendespite their communication difficulties. Recent studies on the care ofchildren with multiple disabilities (San Salavadour 2000; Scelles 2003;Camelio 2006; Pautrel, 2009) have used the children’s entourage to accesstheir feelings. The entourage is considered to be a translator of the child’sfeelings because it understands his or her non-verbal language (Camelio,2006). Using this methodology, four parents and four professionals wereinterviewed in semi-structured interviews which were subjected to aqualitative analysis. The purpose of this research was to identify signs ofpotential psychological suffering and the meaning attributed to thesesigns by the entourage. Each sign was explored across differentdimensions: the context in which the sign is expressed, the meaningattributed to it by the entourage and the valuewhich they considered it tohave (correctly or incorrectly), and finally the entourage’s response to thechild and how it evaluated the relevance of the response (appropriate orinappropriate). This exploration of signs allowed us to consider theentourage’s interpretations and to evaluate the relevance of theirinterpretations. In this way we also allowed for possibility of projections,doubts and errors of interpretation on the part of the entourage. Thirteenchildren were involved, and twelve of them were described as havingshown signs of psychological distress. Six lysosomal diseases wererepresented. The signs which were mentioned included both active

modes of expression (agitation, screaming, crying) and passive modes(no communication, withdrawal, lack of facial expression). Passive signswere often mentioned in cases of deep psychological distress. Themeanings given to these signs were: fear, anxiety, distress, sadness,depression, stress, anger and frustration. Responses included socializing;providing comfort and references; meeting basic needs; administeringmedication. Antidepressant drugs were prescribed for two purposes:either for an anticonvulsive-antidepressant effect, or after painkillers hadproven ineffective. Three contexts that may promote psychologicaldistress were identified: epilepsy, pain and disease progression. Moreextensive research will permit us to carry out the quantitative analysisneeded to test the relevance of each of these three contexts and toevaluate the prescription of antidepressants.

doi:10.1016/j.ymgme.2013.12.091

80Tissue-specific X chromosome inactivation studies as a decision-making criteria for enzyme replacement therapy in femaleheterozygotes for Fabry disease

Dominique P. Germain, Lucia Echevarria, University of Versailles,Montigny, France

Background: Fabry disease is an X-linked disorder caused by thedeficient activity of lysosomal α-galactosidase A. Although histori-cally described as ‘asymptomatic carriers’, heterozygotes can developa wide range of clinical signs and symptoms. The wide clinicalspectrum has been attributed to X chromosome inactivation (XCI),although this hypothesis remains controversial.

Aim: To evaluate the importance of XCI in the clinical phenotypeof heterozygotes and its potential interest in deciding for eligibilityfor enzyme replacement, considering for the first time intra-individual tissular differences of XCI.

Methods: Forty-one heterozygous females were enrolled in thestudy. Exhaustive renal, cardiac and central nervous system work-up,together with 2 global severity score indexes (MSSI and DS3) wereused to assess the clinical phenotype. The methylation status of Xchromosome was studied in 4 different tissues.

Results: Differences in XCI patterns existed between tissues.Twenty-eight heterozygotes were found to be randomly inactivatedin at least 3 tissues, 13 patients had two or more tissues with skewedinactivation. An age-dependant worsening of clinical severity scores,cardiac mass and renal function was found in randomly inactivatedpatients, consistent with progressive accumulation of Gb3. Incontrast, no age correlation could be found in patients with skewedinactivation, whose clinical phenotype was attenuated when thewild-type GLA allele was predominantly expressed. Residual enzymeactivities correlated with inactivation profiles.

Discussion: XCI appears as a prognostic factor of Fabry diseaseprogression in heterozygotes. We proposed XCI to be integrated inthe decision-making criteria of eligibility for enzyme replacement inthis subset of patients.

doi:10.1016/j.ymgme.2013.12.092

81Living in the light of rare and orphan diseases

Levi G. Gershkowitz, Independent (photographer and researcher),Baltimore, MD, USA

Abstracts S45