P88 – 2855: Deficient alpha-dystroglycan presenting with rhabdomyolysis

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and antiepileptic medication was stopped. Besides microcephaly the development is age-appropriate up to now. Asymptomatic cholelithiasis persisted despite therapy with ursodeoxycholic acid. Echocardiography was normal. Genetic analysis revealed two novel, disease-causing mutations in the ACSF3 gene and led to the diagnosis auf CMAMMA. Excretion of MMA in urine decreased spontaneously. A mild protein restricted diet was started. A younger sister also presented generalized seizure and elevated MMA in urine at the age of four weeks. Her genetic analysis is in progress. Conclusion: We found two novel mutations in the ACSF3 gene which we assume to cause a non-classic CMAMMA phenotype.

P85 - 2818 Nonketotic hyperglycinemia: A cause of severe epileptic encephalopathy and hypotonia in children Ç.G. Sel, M. Kiliç, S. Ceylaner, M. Özkan, A. Aksoy, D. Yüksel, K. Karlı Oguz. Dr. Sami Ulus Pediatric Hospital Pediatric Neurology Department Objective: Nonketotic hyperglycinemia is an autosomal recessive metabolic disorder characterized by the accumulation of glycine in all body tissues especially the central nervous system. It is considered a rare disorder, but the exact worldwide incidence is not known. Methods: In this report, we present 5 cases of classical nonketotic hyperglycinemia referred to our pediatric hospital. These patients were diagnosed in the last three months in our center in the capital city of Turkey. The patients’ common findings were severe hypotonia, head lag, poor sucking and intractable seizures. Only one patient had hiccups in the neonatal period. The other 4 patients had flexor and mixed spasms. The patient with hiccups developed asymmetric tonic spasms after 1 month. All patients were taking multiple antiepileptic drugs for their seizures before the diagnosis. All the patients’ cerebrospinal fluid to plasma glycine ratio was over 0.08 at the diagnosis. The initial ratio of the patient with hiccups was 0.031 (over 0.02), but the second evaluation ratio was over 0.08. 2 of 5 patients are mutation positive. The first patient’s mutations in the AMT gene are p.E211K homozygous and p.R320H heterozygous. The other patient’s mutation in the GLDC gene is p.D880E heterozygous. The other 3 patients’ mutation analyses are on research. 4/5 patients have also been evaluated with MRS consolidating the diagnosis. Results: All of the 5 patients were seizure free after Na benzoate treatment for a while. Conclusion: We speculate that glycine encephalopathy is not a rare neurometabolic disorder in our ethnical geography. We should be aware of this disorder if the baby is severe hypotonic and should early evaluate EEG records even without clinical seizures. We offer that cerebrospinal fluid to plasma glycine ratio should be evaluated more than once if there is a strong clinical suspicion.

P86 - 2820 Clinical and biochemical profile of peroxisomal disorders in infancy and childhood L. Mansour, E. Fateen, M. Rashed, H. Marzouk, D. Hesham, L. Tarek. Department of Pediatrics, University of Cairo, Cairo, Egypt Objective: To highlight the clinical and biochemical workup of peroxisomal disorders for proper diagnosis, hence screening for asymptomatic siblings to allow early management. Methods: 24 cases whose ages ranged from 4 months to 9 years (21 males & 3 females) presenting with variable neurological manifestation e.g. seizures, visual, hearing, defect, delayed milestones, hypotonia and disturbed gait. They were subjected to history taking and neurological examination, MRI brain, ophthalmologic exam, very long chain fatty acid assay (VLCFA), abdominal ultrasound (4 cases), skeletal survey (1 case), Adrenal profile (19 cases),

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metabolic screening TMS/MS (4 cases) VEP and ABR in 8 cases. Results: Dysmorphic features, hypotonia and hepatomegaly were present in 4 cases and Ataxia (13 cases). MRI brain revealed abnormal white matter signal suggestive of adrenoleukodystrophy (ALD) in 19 cases. Fundus examination revealed retinitis pigmentosa in two cases & pallor of optic disc (2 cases). Adrenal profile showed hypofunction in 8 cases and ABR revealed hearing loss in 6 cases. Skeletal survey showed calcific foci in the joints in one case. VLCFA were abnormal in all casas with increased C24:0,C26:0, ratio, C24:0/C22:0, C26:0/C22 (23 cases) and increased phytanic acid in one case. Accordingly, identified, Peroxisomal disorders were: Zellweger spectrum in 4 cases, chondrdysplasis punctate (1) and ALD (19 cases). Conclusion: MRI brain is helpful for detection of white matter diseases. Zellweger spectrum should be considered in cases with generalized hypotonia,dysmorphic features, hepatomegaly (PBD) and associated with abnormal VLCFA. Elevated VLCFA is highly reliable for diagnosis of ALD. Early diagnosis of ALD is very important to allow for BMT. Screening of siblings is mandatory for detection of asymptomatic cases.

P87 - 2840 Establishment of rare diagnoses is possible in countries with limited resources L. Yepiskoposyan, B. Sukhudyan. Department of Pediatric Neurology, Arabkir MC and Institute for Child and Adolescent Health, Yerevan, Armenia Objective: Globoid cell leukodystrophy is a rare autosomal recessive lysosomal storage disorder caused by the deficiency of galactocerebrosidase. Methods: This report describes a case in which clinical and MRI picture lead to the direct diagnosis. Results: 12 months old girl presented with loss of developmental milestones. Her development was not concerning until 4 months. Starting from that age she started to have difficulties in head control, lost emotional contact, later she started to have difficulties with swallowing and myoclonias. Examination revealed absence of head control, short fixation and eye tracking movements, spastic quadriparesis, startle myoclonic reflex to auditory stimuli, absence of TDRs from legs. NCS showed distal symmetrical demyelinating polyneuropathy. Brain MRI showed supratentorial and vermian atrophy, abnormal signal from PLIC, increased T2 signal from periventricular white matter (with sparing of subcortical U-fibers), enlargement of optic nerves and chiasm, bilateral areas of T2 hyperintensity in the dentate hilum and cerebellar white matter, hypointensity in the peridentate area. Brain CT scan was done for possible calcifications in basal ganglia (to exclude Aicardi-Goutières syndrome), which surprisingly revealed communicating obstructive hydrocephalus. We went through the literature and found that the latter was also described in some cases of globoid cell leukodystrophy. Decreased galactocerebrosidase activity in leukocytes confirmed the diagnosis of Krabbe disease. Conclusion: In developed countries this patient would undergo full metabolic screening to exclude most relevant possible diagnoses, but physicians in developing world are forced to put together clinical picture and other findings to reach to the most likely diagnosis, which is a very important step to narrow the list of differential diagnosis and costs of needed investigations.

P88 - 2855 Deficient alpha-dystroglycan presenting with rhabdomyolysis A. Kuster, G. Caillaux, F. Leturcq, N. Romero. Pediatric Intensive Care Unit, University Hospital of Nantes, Nantes, France Objective: To describe a case of deficient alpha-dystroglycan revealed by acute rhabdomyolysis. Rhabdomyolysis frequently

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occurs in metabolic myopathies induced by exercise or triggered by intercurrent disease. Furthermore, rhabdomyolysis has been described in muscular dystrophies, particularly Duchenne and Becker dystrophies. It has only rarely been reported in limb girdle muscular dystrophies (LGMD), even though it may be the first and unique presenting feature of some type of LGMD. Case description and results: A 12 year old boy complained about fatigue after summer holidays with more intensive exercise than usually. As laboratory investigations showed mild elevation of serum AST (264 IU/l, N<31) and ALT (150 IU/l, N<34), he was referred to abdominal ultrasound, during which myoclonic movements were observed. CK levels were therefore determined and very raised levels were found (10000IU/l). Intensive metabolic work-up found no argument for a fatty acid oxidation disorder, mitochondrial disease or a LPIN1 mutation, and muscular biopsy was performed in view of persistent mildly raised CK levels. Alpha-dystroglycanopathy was diagnosed based on absent alpha-dystroglycan expression on immunohistochemistry, confirmed by Western blotting. Electroneuromyogramme revealed normal and further investigations for a drop-foot gait revealed mild multifocal periventricular white matter abnormalities on cerebral MRI. Cardiomyopathy was not found associated with LGMD2I in this patient. Conclusion: Limb girdle muscular dystrophy type 2I (LGMD2I) is one of the most common autosomal recessive limb girdle muscular dystrophies presenting in childhood. It may present with acute rhabdomyolysis as the first sign. It should be included in the diagnostic work-up of rhabdomyolysis and persistent high CK levels should prompt muscle biopsy and/or molecular diagnosis.

P89 - 2878 Neuronal ceroid lipofuscinosis-2 (CLN2) natural history and path to diagnosis: International experts’ current experience and recommendations on CLN2 disease, a type of Batten disease, resulting from TPP1 enzyme deficiency A. Schulz, N. Miller, S.E. Mole, J.L. Cohen-Pfeffer. Department of Paediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Objective: Describe current practices and challenges related to diagnosis and natural history of CLN2 disease. Methods: 18 international neuronal ceroid lipofuscinosis experts (clinicians, academic researchers, and diagnostic laboratory directors) answered a comprehensive survey on CLN2 disease. Topics included classification, natural history and path to diagnosis. Results: Although a diagnostic algorithm exists, clinical suspicion for CLN2 disease is low. The majority responded that patient referral to a knowledgeable specialist can take longer than one year and identified delays in clinical suspicion of CLN2 as a critical barrier to diagnosis. On average, a 2–3 year delay exists between first onset of symptoms and diagnosis. 84% of experts performed either a TPP1 enzyme activity test and/or a molecular test to confirm diagnosis. The group described the gold standard for diagnosis as demonstration of decreased TPP1 enzyme activity and/or detection of two pathogenic mutations in the TPP1/CLN2 gene. Initial presenting symptoms were identified as epilepsy/seizures (86%), speech decline (64%), and delay/regression in development (50%). CLN2 symptoms were reported to develop between 18 months and 5 years of age most commonly, although 23% of experts noted that some patients present with symptoms later in life. Experts agreed that the most impactful strategies in managing patients with CLN2 disease were use of antiepileptic drugs (100%), gastric tubes (86%), and physical/occupational therapy (57%). Despite this management approach, 67% thought CLN2 patients’ seizures were relatively treatment-resistant. Conclusion: CLN2 disease is a severe, progressive neurodegenerative disorder: patients typically experience uncontrolled seizures, rapid deterioration of motor and cognitive functions, gradual loss of vision, and pre-

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mature death. Disease awareness is low among non-expert clinicians, resulting in delays in diagnosis and referrals. These survey data suggest that worldwide education regarding CLN2 disease is necessary to support timely diagnosis so that future therapeutic options may be initiated early in the disease course.

P90 - 2900 Menkes disease with atypical findings in neuroimaging: It’s not only gold that glitters M.A. Fernández-García, V. Cantarín-Extremera, L. López-Marín, J.J. García-Peñas, S. Jiménez-Echevarría, L. González-Gutiérrez-Solana, L. Babín-López, M. Hortigüela-Saeta, S. Rekarte-García, I. Bermejo-Arnedo, I. Pérez-Sebastián, M.A. López-Pino. Department of Pediatric Neurology, Hospital Infantil Universitario Niño Jesús, Madrid, Spain Objectives: To present a case of Menkes disease (MD) with atypical findings in neuroimaging and review the publications related to these findings. Method: Systematic literature review and retrospective description of the case seen at our center. Results: We present the case of a 3-month-old infant admitted at our Intensive Care Unit with status epilepticus. Initial brain magnetic resonance (MR) studies revealed the coexistence of an extensive T2 hyperintensity in the temporal white matter (WM) and in both caudate nuclei. Neurological examination showed marked psychomotor retardation, with no exploratory behaviour, severe hypotonia and swallowing difficulties. Complementary tests revealed decreased ceruloplasmin levels (3.6 mg/dL -normal: 39–51 mg/dL), increased lactate in cerebrospinal fluid (40 mg/dL), “Pili torti” on microscopic examination of the hair and a mutation in the gene ATP7A, which confirmed the diagnosis of MD. Treatment was iniciated with copper histidinate and three antiepileptic drugs (Levetiracetam, Lacosamide, and Clobazam). By the age of 6 months, MR studies revealed the disappearance of hyperintensities on WM and basal ganglia (BG), with marked atrophy and bilateral subdural hygromas. A rapidly deteriorating condition led to exitus at 8 months. Conclusion: Neuroradiological atypical findings in MD published so far involve leukoencephalopathies (located in the temporal lobe, periventricular or diffuse), and BG anomalies, such as infarcts or cytotoxic lesions. As the presented case shows, and according to other cases published, there can be early damage in WM and BG in MD instead of the typically observed cortical atrophy and vascular abnormalities. The pathogenic mechanism could involve vasogenic edema caused by the initial status epilepticus, and cytotoxic damage of both caudates as a result from energetic failure. Thus, predominant diffuse involvement of the WM in the absence of cortical atrophy or vascular tortuosity should not exclude the diagnosis of MD, even in late infancy, when the clinical and biochemical picture supports it.

P91 - 2939 A novel mutation in the TK2 gene and clinical phenotype in Spanish patients F.J. Ramos, J. Dominguez, R. Marti, C. Ortez, J. Montoya, C. Jou, M. O’Callaghan, D. Yubero, R. Montero, J. Armstrong, R. Artuch, A. García-Cazorla, J. Colomer, A. Nascimento, C. Jimenez Mallebrera. Hospital Sant Joan de Deu, Neurometabolic Unit, Barcelona, Spain Objective: The aim of this study is to describe the phenotype of 4 Spanish patients and the finding of a novel mutation in TK2 gene. Methods: We report 4 unrelated male patients from non-consanguineous families. Details of the clinically features, biochemical, anatomy pathology and genetic findings are presented. Results: 3/4 showed a similar phenotype with normal early development until a progressive hypotonia and muscular