P05.11 Miglustat treatment in Niemann-Pick disease type C (NP-C): Clinical experience in two patients

S52 neuronopathic symptoms which present with a wide phenotypic spectrum, from perinatal lethal forms with progressive neurological involvement to later-onset, nonneuronopathic forms. GD is characterized by significant genotypic heterogeneity among clinically similar patients and different phenotypes among patients with the same mutations. We report a 3 months old girl who presented at birth with petechiae, splenomegaly (2 cm) and thrombocytopenia (40 × 109 /L). During the following period, hepatosplenomegaly progressed rapidly (palpatory-liver 7 cm, spleen 10 cm) and apparent severe pancytopenia was noted (Hb 62 g/L, leukocytes 3.7 × 109 /L, granulocytes 1.4 × 109 /L, platelets 28 × 109 /L). Serum and CSF chitotriosidase activity was markedly elevated (300x-control and 8x-control respectively). WBC b-glucocerebrosidase activity was diminished (15−20% of control). Gene analysis revealed homozygosity for a compound mutant allele H255Q+D409H. This genotype generally correlates with acute neuronopathic-type 2 disease. However, slow progressive type 2/3-like disease has been reported as well. We are faced with a child who doesn’t have neurological problems as yet, who has a normal EEG and brain MR. Consequently, enzyme replacement therapy (Cerezyme® 80 IU/kg/10days) at age 1.5 months was introduced, which has already reduced hepatosplenomegaly (palpatory-liver 5 cm, spleen 7 cm), serum chitotriosidase (5xlower) and improved blood counts (Hb 88 g/L, leukocytes 4.3 × 109 /L, platelets 121 × 109 /L). Since neurological symptoms have not developed, we are considering an umbilical cord blood stem cell transplantation, a procedure that has been successfully attempted in presymptomatic patients with Krabbe disease. P05.11 Miglustat treatment in Niemann-Pick disease type C (NP-C): Clinical experience in two patients G. Haliloglu1 *, A. Yuce2 , F. Gurakan2 , M. Topcu1 . 1 Department of Pediatric Neurology, Hacettepe University, Children’s Hospital, Turkey, 2 Department of Gastroenterology, Hacettepe University, Children’s Hospital, Turkey Background: NP-C is a neurovisceral lysosomal storage disease caused by mutations in NPC1 or NPC2, which encode proteins involved in intracellular lipid trafficking. Miglustat, inhibits glucosylceramide synthase, the enzyme involved in the first step of glycosphingolipid synthesis, and is recently approved in the EU for the treatment of progressive neurological manifestations in adult and pediatric patients with NP-C. Case presentations: Among 19 patients diagnosed with NPC in our center, three of our patients are on miglustat treatment. We will discuss in detail clinical and laboratory findings and effect of treatment in two of these patients (genotype: NPC1) with 4 months and 17 months followup. The first patient is a 18-year old boy, who presented with walking difficulties at the age of 11 years, diagnosed at the age of 14 years with pyramidal, extrapyramidal, cerebellar findings and vertical supranuclear gaze palsy. He developed cerebellar atrophy. On 4th month of treatment, he had improvement in mood, daily activities, to some extent in extrapyramidal involvement. The second patient is a 48/12-year-old girl, diagnosed at the age of 3 years when she presented with hypotonia, developmental delay and splenomegaly. On 17th month of treatment, she is at the level of a 3-year-old child, with a prominent decrease in frequent falls. Splenomegaly is detected by ultrasonography. Conclusions: Miglustat is effective, well tolerated without significant side effects in our patients and stabilizes neurological status during their follow-up. Further evaluation of these patients is required for long-term effects. Early diagnosis is crucial in the era of SRT.

Poster sessions P05.12 The first case of genetically proven variant late-infantile neuronal ceroid lipofuscinosis in Bulgaria harbors the founder CLN7/MFSD8 mutation in Roma P. Stefanova Dimova1 *, M. Kousi2 , V. Bojinova3 , Z. Lukacs4 , A.-E. Lehesjoki2 . 1 Clinic of Child Neurology, St. Naum University Hospital of Neurology and Psychiatry, Bulgaria, 2 Folkhalsan Institute of Genetics, Department of Medical Genetics and Neuroscience Center, University of Helsinki, Finland, 3 Clinic of Child Neurology, St. Naum University Hospital of Neurology and Psychiatry, Bulgaria, 4 Department of Paediatrics, Metabolic Laboratory, University Hospital Hamburg Eppendorf, Hamburg, Germany Background: Variant late-infantile neuronal ceroid lipofuscinosis (vLINCL) is genetically heterogeneous. To date, 23 mutations in MFSD8/CLN7 gene have been identified in patients of various ethnic origins. The missense change c.881C>A was proven to be a founder mutation in Roma patients from former Czechoslovakia. Aim of the study: To present the first Bulgarian patient with genetically confirmed diagnosis of vLINCL harboring the founder Roma mutation. Material and Methods: A boy of Roma origin had uneventful development till the age of 4 years, when rapidly progressive visual loss was noted. One year later, refractory epileptic seizures added on and brain computed tomography revealed cerebellar atrophy. At the age of 6, progressive mental and motor decline in the form of speech regression, ataxia, and quadriparesis developed as well. Brain magnetic resonance imaging demonstrated global atrophy and periventricular leucoencephalopathy. Results: Common leucodystrophies, subacute sclerosing panencephalitis and classical NCL forms were excluded by the normal results of metabolic screening, cerebrospinal fluid examination for morbilli-virus antibodies and enzymatic assay of palmitoyl-protein thioesterase I and tripeptidyl peptidase I activity, respectively. Genetic testing for vLINCL was done by sequencing the genes MFSD8/CLN7 and CLN8 from genomic DNA. The sequence analysis revealed that the child was homozygous for the MFSD8/CLN7 mutation c.881C>A. Conclusions: Although isolated, our case implies that c.881C>A mutation in MFSD8/CLN7 is a founder gene defect in geographically distant Gypsy groups and thus adds evidence for the common origin of the founder Roma population in Europe. For this population CLN7/MFSD8 screening should be considered an important diagnostic alternative in LINCL cases. P05.13 Coexistence of Krabbe’s disease and multiple chromosomal abnormalities: a case report T.H. Yeo1,2 *, E. Wong2 , C. De Goede2 . 1 Department of Paediatric Neurology, Royal Manchester Children’s Hospital, Manchester, United Kingdom, 2 Department of Paediatric Neurology, Royal Preston Hospital, Preston, United Kingdom Introduction: Krabbe’s disease is an autosomal recessive disorder that is due to galactocerebrosidase gene mutations. The characteristic features include early progressive spasticity, excessive irritability and developmental regression. Duplication 4p has a spectrum of phenotypic presentations, including characteristic dysmorphism, microcephaly, postnatal growth retardation and psychomotor retardation. We describe an infant with initial clinical features and chromosomal analysis which suggested Duplication 4p. But subsequent clinical course and neurometabolic investigation led to a diagnosis of Krabbe’s disease. Case Report: Our patient is a first male born to his healthy Caucasian non-consanguineous parents. No significant family history of illnesses. At 2-month old, he presented