M. Kyriazi

Moyamoya syndrome and neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is the most prevalent autosomal dominant genetic disorder among humans. NF1 vasculopathy is a significant but underrecognized complication of the disease, affecting both arterial and venous blood vessels of all sizes. Moyamoya syndrome is a cerebral vasculopathy that is only rarely observed in association with NF1, particularly in the pediatric age range. Herein, we report of a 5-year-old female with NF1 and moyamoya syndrome and we briefly review the existing literature.

Nephrocalcinosis and Renal Failure in Lesch-Nyhan Syndrome: Report of Two Familial Cases and Review of the Literature

Lesch-Nyhan syndrome is an X-linked recessive inborn error of purine metabolism, due to deficiency of the enzyme HPRT (hypoxanthine-guanine phosphoribosyl transferase) and underlying HPRT gene mutations (over 300 mutations identified up to date). It is characterized by a wide range of neurological symptoms and signs (mainly a combination of spastic diplegia with choreoathetosis and an overall psychomotor redardation). Herein, we report of two cousins with Lesch-Nyhan syndrome and a confirmed novel HPRT gene mutation: c.65T>C, who both developed nephrocalcinosis and renal failure, findings not been previously published in children with HPRT deficiency.

PP15.6 – 2468: Changes in cognitive performance in children and adolescents with neurofibromatosis type 1

Objectives Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with a prevalence of approximately 1:3500. There is evidence to suggest that children and adolescents with NF1 present with lower cognitive skills than healthy controls and with higher cognitive skills than peers with other genetic disorders affecting the central nervous system. Our goal was to explore if there are any changes in the cognitive skills of children with NF1 as they grow older. Methods Eight children with NF1 participated in the study. The diagnosis was made based on NIH criteria and they did not present with any comorbidity. They were examined twice in a period of 3–5 years using Wechsler Intelligence Scale for Children to assess their Intelligence Quotient, which is the most widely accepted indication of cognitive performance. Related-sample t-tests were applied to explore if there were differences both in overall as well as in individual scores and if these differences were statistically significant. Results The differences that were detected in the overall and the individual scores between the two assessments were not statistically significant for any of the children or adolescents with NF1. Conclusions This study demonstrated that children and adolescents with NF1 without comorbid conditions do not experience cognitive decline due to their genetic disorder. More research is needed in larger cohorts of children and adolescents with NF1 and comorbid conditions to explore if there is a cognitive decline and to which extent it can be treated with appropriate interventions.

PP12.13 – 2362: The influence of motor and vocal tic severity on children's quality of life

Objective To assess the influence of motor and vocal tic severity on childrens quality of life (QOL). Methods Forty six children were assessed (61% boys, 39% girls), aged 3.5–15.5 years old. Twenty five children (54%) presented with both motor and vocal tics, eighteen children (39%) with only motor tics and 3 children (7%) with Tourettes disorder. The motor and vocal tic severity was assessed with Yale Global Tic Severity Scale (YGTSS), while the quality of childrens life was assessed with KIDSCREEN-52 QOL questionnaire. By using linear regression we examined if the factors: age, sex, motor tic severity (of YGTSS), vocal tic severity, total tic severity score, impairment, total Yale Global Tic Severity Scale Score, affect the QOL of children with tics. Results The only dimensions of childrens QOL that were affected were autonomy and financial resources. Furthermore, on dimensions: physical well-being, moods and emotions and autonomy the older the child was the worse was his/her QOL. In relation to the kind of tic, the severity of vocal tics correlated significant (p Conclusion There is an evident lack of studies that examine QOL in children with tics. The severity of motor and vocal tics affect negatively childrens QOL on multiple dimensions. Childrens age is not only a correlative but also a predictive factor: predicting a worse QOL in older children, one could select older children in need for more aggressive psychological intervention.

PP03.13 – 2568: Two further Greek cases of Krabbe disease and a new mutation in the GALC gene

Objective Krabbe disease is an autosomal recessive neurodegenerative disorder due to a defect of the lysosomal enzyme galactocerebrosidase (GALC) and is classified into infantile and late-onset form, depending on the age of onset. Methods and results We report two Greek patients with Krabbe disease with the infantile and late-infantile forms, respectively. The first patient was admitted at the age of 3.5 months, due to generalized hypertonia and developmental delay. A brain MRI demonstrated signs of leukodystrophy, while nerve conduction velocities (NCVs) were significantly decreased. A severe reduction in â-galactocerebrosidase activity (0.003 nmol/mg protein/hr, normal range 0.1–0.97 units), indicated the diagnosis of Krabbe disease, which was confirmed by molecular genetic testing (an homozygous c.411_413delTAA [K139del] mutation in the GALC gene). The second patient manifested with psychomotor regression at the age of 6 months, while the brain MRI was normal. At the age of 18 months, a repeated brain MRI demonstrated leukodystrophic changes, whereas NCVs were significantly delayed, too. A total lack of â-galactoserebrosidase activity (0.00 nmol/mg protein/hr, normal range 0.1–0.97 units) led to further molecular genetic testing, which revealed a homozygous c.749T>C [p.I250T] mutation in the GALC gene. At their last follow-up visit at the age of 4 and 10 years, respectively, both patients were bed-ridden and demonstrated the clinical picture of spastic tetraplegia suffering from frequent infections of the respiratory tract and fed through a gastrostomy catheter. Conclusion The c.411_413delTAA [K139del] mutation is the first reported in the literature, while there are another two reports of patients bearing the c.749T>C [p.I250T] mutation. Interestingly, both these patients were of Greek ancestry, a fact that could be indicative of a founder effect. Genotyping of patients of Krabbe disease is important, in order to contribute to a European mutation database and to further study possible genotype-phenotype correlations.