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P319 Gaucher disease type III with craniosynosteosis
S120 and NPC2 that play a role in intracellular cholesterol and glycolipid trafficking. We would like to present atypical clinical and neurological findings of our 15 patients (9 boys and 6 girls) with molecularly confirmed NPC. Among these patients, 8 were followed up in gastroenterology department. Initial diagnoses of remaining patients were cerebral palsy and/or epilepsy in all. Mean of current age of the patients is 13 y (4−23 y). Mean age of the patients at presentation is 6 y (2−11 y), and at the time of diagnosis is 10 y (4−18 y). Mean of time lag between onset of symptoms and diagnosis is 3.8 y (1−12 y). There is first-degree consanguinity in all of the families except one. Clinical findings are hypotonia, ataxia and gaze palsy (n = 1), drug-resistant seizure disorder with continuous spike and wave activity during sleep (CSWS), self mutilation, hyperactivity and severe mental retardation with behavioral problems (n = 1), vertical gaze palsy and movement disorder (n = 2), narcolepsy and splenomegaly (n = 1), learning disability, hand tremor, pseudobulbar involvement with dysarthria and feeding difficulties (n = 1), tremor and head drops (n = 1). MRI features are cerebellar atrophy (n = 1), posterior periventricular leukodystrophy, cerebral and hippocampal atrophy (n = 1), cerebellar and corpus callosum atrophy (n = 1), and normal (n = 2). Final diagnosis was done by bone marrow aspiration showing foamy cells and skin fibroblast cultures showing impaired cholesterol esterification and low sphingomyelinase activity. Hepatosplenomegaly and fetal ascites in the perinatal and infancy period, hypotonia, ataxia and gaze palsy after the age of 2 years, extrapyramidal movement disorder, vertical gaze palsy in late adolescence may be clues for diagnosis. P319 Gaucher disease type III with craniosynosteosis D.I. Zafeiriou1 *, E. Vargiami1 , A. Anastasiou2 , A. Ververi1 , E. Michelakaki3 , N. Gombakis1 . 1 1st Department of Pediatrics, Aristotle University, Thessaloniki, Greece; 2 Department of Radiology, “Hippokratio” General Hospital, Thessaloniki, Greece; 3 Institute of Child Health, Athens, Greece Gaucher disease type 3 (GD3) is a rare inherited recessive autosomal metabolic defect, due to a deficiency of bglycocerebrosidase. It manifests in childhood leading to subacute neurological symptoms. Objective: To present a Greek case of GD3 with a wide range of neurological symptoms, who additionally manifested acquired microcephaly due to craniosynostenosis. Case report: A 9 month-old female presented with sudden onset of strabismus and occasional head thrusting. A cranial MRI demonstrated mild white matter periventricular lesions. Otherwise, her development was considered normal till the 18th month, since she spoke and walked independently at 15 months of age. During the next months growth retardation and neurological decline became evident. At 18 months, her neurological picture consisted of strabismus, tremor, myoclonus, hypertonia, pyramidal tract signs, horizontal supranuclear gaze palsy, ocular apraxia, and intellectual impairment. Additionally she demonstrated massive visceral enlargement, omphalocele, lymphadenopathy, growth retardation and progressive microcephaly. A 3D-CT scan demonstrated craniosynostosis of all cranial sutures. Laboratory analysis demonstrated mild anemia and moderate thrombocytopenia. Glucosylceramide concentration in leukocytes and chitotriosidase activity in plasma were diagnostic of Gaucher disease. Molecular genetic defined the gene defect (mutations Y108C and D409H+H255Q), thus classifying the patient under GD3. Enzyme replacement therapy (ERT) was initiated after the diagnosis with a high initial dosage (120 mg/kg, biweekly). Two years after initiation of ERT (with regular clinical and biochemical follow-up), her neurological picture has slightly
Posters worsened, while her systemic manifestations demonstrate a clear-cut improvement. Conclusions: GD3 presents with a wide range of neurological symptoms. ERT, although beneficial in systemic symptoms of the disease, exerts no effect in CNS manifestations. The unique finding of craniosynosteosis (first report) could be either attributed to Gaucher disease (due to proliferation of Gaucher cells at the cranial sutures) or could be simply explained by chance alone. P320 A treatable metabolic myopathy: riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency and coenzyme Q10 myopathy G. Haliloglu1 *, B. Talim2 , M. Topcu1 , G. Kale2 , H. Topaloglu1 . Pediatric Neurology, Hacettepe Children’s Hospital, Ankara, Turkey; 2 Pediatric Pathology, Hacettepe Children’s Hospital, Ankara, Turkey 1
Metabolic myopathies represent a group of heterogeneous muscle disorders characterized by impairments in intermediary metabolism dur to defects in glycogen, lipid, purine metabolism or abnormalities in mitochondrial electron transport chain. Clinically a variety of neuromuscular presentations are seen at different ages of life. Hypotonia and multisystem involvement in the newborn and infancy period, exercise intolerance with or without progressive muscle weakness and myoglobinuria later in life are common presentations. From a clinical point, it is utmost important to recognize these disorders since a sub-group have specific treatment. We would like to present 9 patients (8 girls, one boy) from 7 different families with lipid myopathy and clinical improvement after riboflavin and coenzyme Q10 substitution. Age at presentation varied between 2−14 years. Clinical and laboratory findings at presentation were exercise intolerance and proximal weakness (n = 3), sudden onset of severe weakness (n = 1), mild non-progressive weakness (n = 3), high CK level in all. Muscle biopsy showed lipid storage in muscle (n = 7), few COX negative fibers (n = 2) with degeneration in some. Urine organic acid analysis and plasma acyl-carnitine profiles indicated multiple acyl-CoA dehydrogenation deficiency in 4 families with proven ETFDH mutations. In two families there was isolated complex I deficiency. In the remainder one family molecular analysis is pending. There had been full response to riboflavin and coenzyme Q10 treatment in all patients with both a clinical improvement and normalization of serum CK levels. Myopathic form of coenzyme Q10 deficiency caused by mutations in ETFDH gene is allelic to glutaric aciduria type II. CoQ10 and riboflavin supplementation should be considered in patients with lipid myopathy as a long-term treatment. P321 Withdrawn P322 Pompe Disease: a spectrum of phenotypes. Effect of enzyme replacement therapy (ERT) D. Lianou1 *, D. Syrengelas2 , M. Garatzioti1 , I. Akritidou1 , M. Brokalaki1 , H. Michelakakis3 . 1 1st Paediatric Department “Aghia Sophia” Childrens Hospital, Athens, Greece; 2 Department of Pediatric Physical Therapy “Aghia Sophia” Childrens Hospital, Athens, Greece; 3 Enzymology and Cellular Function, Institute of Child Health, Athens, Greece Objective: To present the heterogeneous clinical presentation of 2 patients with infantile-onset Pompe Disease (PD) and the efficacy of ERT in both patients. Methods: Alberta Infant Motor Scale (AIMS) was used for the gross motor assessment and left ventricular mass index (LVMI) for cardiac mass evaluation in both patients.
Posters worsened, while her systemic manifestations demonstrate a clear-cut improvement. Conclusions: GD3 presents with a wide range of neurological symptoms. ERT, although beneficial in systemic symptoms of the disease, exerts no effect in CNS manifestations. The unique finding of craniosynosteosis (first report) could be either attributed to Gaucher disease (due to proliferation of Gaucher cells at the cranial sutures) or could be simply explained by chance alone. P320 A treatable metabolic myopathy: riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency and coenzyme Q10 myopathy G. Haliloglu1 *, B. Talim2 , M. Topcu1 , G. Kale2 , H. Topaloglu1 . Pediatric Neurology, Hacettepe Children’s Hospital, Ankara, Turkey; 2 Pediatric Pathology, Hacettepe Children’s Hospital, Ankara, Turkey 1
Metabolic myopathies represent a group of heterogeneous muscle disorders characterized by impairments in intermediary metabolism dur to defects in glycogen, lipid, purine metabolism or abnormalities in mitochondrial electron transport chain. Clinically a variety of neuromuscular presentations are seen at different ages of life. Hypotonia and multisystem involvement in the newborn and infancy period, exercise intolerance with or without progressive muscle weakness and myoglobinuria later in life are common presentations. From a clinical point, it is utmost important to recognize these disorders since a sub-group have specific treatment. We would like to present 9 patients (8 girls, one boy) from 7 different families with lipid myopathy and clinical improvement after riboflavin and coenzyme Q10 substitution. Age at presentation varied between 2−14 years. Clinical and laboratory findings at presentation were exercise intolerance and proximal weakness (n = 3), sudden onset of severe weakness (n = 1), mild non-progressive weakness (n = 3), high CK level in all. Muscle biopsy showed lipid storage in muscle (n = 7), few COX negative fibers (n = 2) with degeneration in some. Urine organic acid analysis and plasma acyl-carnitine profiles indicated multiple acyl-CoA dehydrogenation deficiency in 4 families with proven ETFDH mutations. In two families there was isolated complex I deficiency. In the remainder one family molecular analysis is pending. There had been full response to riboflavin and coenzyme Q10 treatment in all patients with both a clinical improvement and normalization of serum CK levels. Myopathic form of coenzyme Q10 deficiency caused by mutations in ETFDH gene is allelic to glutaric aciduria type II. CoQ10 and riboflavin supplementation should be considered in patients with lipid myopathy as a long-term treatment. P321 Withdrawn P322 Pompe Disease: a spectrum of phenotypes. Effect of enzyme replacement therapy (ERT) D. Lianou1 *, D. Syrengelas2 , M. Garatzioti1 , I. Akritidou1 , M. Brokalaki1 , H. Michelakakis3 . 1 1st Paediatric Department “Aghia Sophia” Childrens Hospital, Athens, Greece; 2 Department of Pediatric Physical Therapy “Aghia Sophia” Childrens Hospital, Athens, Greece; 3 Enzymology and Cellular Function, Institute of Child Health, Athens, Greece Objective: To present the heterogeneous clinical presentation of 2 patients with infantile-onset Pompe Disease (PD) and the efficacy of ERT in both patients. Methods: Alberta Infant Motor Scale (AIMS) was used for the gross motor assessment and left ventricular mass index (LVMI) for cardiac mass evaluation in both patients.