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Objective Preterm birth is emerging as a major health problem in the developed world. A significant modern risk factor is the widespread use of assisted reproductive technology (ART). We aim to prospectively study the additional risk of ART for developing autistic spectrum disorder (ASD) in comparison to naturally conceived preterm. Methods We prospectively followed 213 children of a cohort of 283 very low birth weight newborns born between 1998 and 2002. Their mean age was 12.8 years, 46% were males and 56% were the result of multiple pregnancies. 33% were conceived by ART while the mean gestational age was 30.8±2.4 and the mean birth weight was 1237±266 grams. The medical charts of all the participants were reviewed for neonatal complications, developmental milestones and current behavioral diagnoses. ASD was assessed using the A.S.S.Q. (Autism Spectrum Screening Questionnaire). Results The incidence of ASD was 24/213 (11.3%) and other neurodevelopmental comorbidities were: attention deficit hyperactivity disorder (ADHD, 26%), learning disabilities (25%), cerebral palsy (CP, 11%), epilepsy (6%) and intellectual disability (3%). No significant differences were found in the incidence of ASD and other neurodevelopmental comorbidities between the ART and naturally conceived groups. The ASD and non-ASD groups did not differ in birth weight, gestational age and Apgar score. However, significant differences were found for male gender (p=0.015), ADHD (p=0.085), epilepsy (p=0.033) and intellectual disability (ID, p=0.004). Conclusion We found the incidence of ASD in a cohort of preterms to be approximately ten times the incidence reported in the general Israeli population. ART was not found to be a risk factor for any neurodevelopmental disorder. ASD was not found to be associated with a lower Apgar score or CP. The association between ASD and male gender, ADHD, epilepsy and ID is well known and also evident in our cohort.

Objective A wide spectrum of Pompe disease exists from the infantile form to a milder juvenile or adult form. The clinical heterogeneity primarily relates to the occurrence of different mutations that lead to a different rate of lysosomal glycogen accumulation and non genetic factors that are thought to modulate the disease phenotypes. Methods We describe two unrelated families from Jordan presenting with the infantile variant form of Pompe disease sharing the same homozygous mutation c.2015 G>A in exon 14. Previously this mutation was described in juvenile onset cases. Results The first family consisted of two female siblings (5.5 and 3.5 years of age) born to first degree cousins of Muslim descent. The elder one presented between 3–6 months of age with marked hypotonia, hypertrophic cardiomyopathy, proximal muscle weakness, motor delay and no DTR's. She was started on enzyme replacement therapy at 24 months of age, walked independently at 27 months. Currently she has a nasal speech, muscle weakness and mild cardiomyopathy. Her younger sister, presented at 3 months with mild hypotonia, motor delay and hepatomegaly. She started ERT at 6 months and currently her neurological examination is normal. The second patient is a 5-year-old boy who presented with hypertrophic cardiomyopathy, hypotonia and an enlarged tongue. His parents are first degree cousins. Two siblings died before the age of one month due to heart failure; He started ERT at 14 months of age, walked independently at 18 months and follow-up echocardiography studies improved markedly. Currently he has a nasal speech, articulation disorder and otherwise no muscle weakness. Conclusion Our cases confirm the phenotypic variability among patients, even carrying the same genotype. Two patients, for whom ERT was commenced later, suffer from nasal speech and severe articulation disorder in spite of improved cardiac and motor function.

Objective A recently described mutation within the newly discovered gene MED17 was found to be responsible for causing primary microcephaly in Caucasus-Jewish families. The gene is located on chromosome 11 and codes for a subunit of the Mediator complex of mRNA synthesis. We describe the clinical course and MRI pattern of a cohort of 12 children of Caucasus-Jewish origin from several unrelated families with the same founder mutation in the MED17 gene. Methods The medical charts of the patients were reviewed as well as their MRI scans and EEG records. Results The cohort consists of 8 males and 4 females from 8 families of which 6 were consanguineous. Their ages range from 6 months to 18 years old. Soon after birth each affected child displayed jitteriness, irritability, poor feeding and increased muscle tone. Head circumference percentiles of all patients were normal at birth and declined within a few months to 6 standard deviations below the mean. The clinical neurological manifestations consisted of progressive spastic quadriplegia, epilepsy and profound psychomotor retardation. Brain MRI revealed marked cerebral and cerebellar atrophy with ventral flattening of the pons consistent with pontocerebellar hypoplasia. The early EEGs showed discontinuous low amplitude dysmature background with intermittent sharp waves and burst suppression evolving to generalized monotonous non-reactive low amplitude background. Conclusion Recognition of the disease and its clinical course is of importance to prevent recurrence among families of Caucasus-Jewish ancestry.

O6-6 Acute neurovascular events in children with ornithine transcarbamylase (OTC) deficiency: a retrospective review A. Brassier2, N. Boddaert3, J.P. Bonnefont4, I. Desguerre1, M. Kossorotoff1 *, P. De Lonlay2,4. 1Neuropediatrics, Necker Enfants Malades, Paris, France; 2Metabolic Disease, Necker Enfants Malades, Paris, France; 3Pediatric Radiology, Necker Enfants Malades, Paris, France; 4Genetics, Necker Enfants Malades, Paris, France