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O6-5 Aromatic L-amino acid decarboxylase (AADC) deficiency: the UK experience
S14 O6-3 Coenzyme Q10 responsive ataxia M.M. O’Callaghan1,3 *, R. Montero2,3 , A. Aracil1 , C. Espinos ´ 1,3 , F. Palau1,3 , P. Navas1,3 , R. Artuch2,3 , M. Pineda1,3 , P. Briones2,3 . 1 Child Neurology, Hospital Sant Joan de D´eu, Barcelona, Spain; 2 Clinical Chemistry Laboratory, Hospital Sant Joan de D´eu, Barcelona, Spain; 3 CIBERER, ISCIII Objective: Coenzyme Q10 (CoQ10) deficiency is a mitochondrial autosomal recessive disease with heterogeneous phenotypes such as Cerebellar Ataxia. Although there is no etiologic treatment for mitochondrial diseases, CoQ10 deficiency may respond to therapy with oral supplementation. The aim of this study is to assess the clinical outcome after CoQ10 therapy in patients presenting congenital ataxia associated with CoQ10 deficiency. Methods: Seven patients presenting congenital ataxia and followed up in our children’s hospital were selected. Other inherited forms of ataxia were excluded. Mitochondrial respiratory chain analysis and coenzyme Q10 concentrations in muscle and fibroblasts were performed. Molecular analysis of four genes involved in CoQ10 biosynthesis pathway was studied in the patients’ samples. The patients received oral supplementation with CoQ10 to 30 mg / kg / day for 2 years. Every 6 months clinical controls consisting neurological exploration, ICARS (International Cooperative Ataxia Rating Scale) and video recording were carried out by the same child neurologist. Brain MRI was performed at the beginning of the study and during follow up. Results: A defect of CoQ10 was found in fibroblasts and muscle of all patients. Clinical improvement was observed in all patients with a decrease of ICARS scores 2 years after CoQ10 oral supplementation. Levels of CoQ10 in blood were higher than initial values. Brain MRI revealed severe cerebellum atrophy in 5 patients and moderate in 2 which persisted despite treatment. Conclusions: ICARS and video recording are useful to evaluate clinical response to supplementation with oral CoQ10. Monitoring CoQ10 levels in blood is helpful to evaluate treatment fulfilment. Deficit of CoQ10 must be suspected in every patient with congenital ataxia when other aetiologies disclosed. Clinical improvement with CoQ10 supplementation should be considered a diagnostic criterion of CoQ10 deficiency. O6-4 The clinical presentation of late infantile and variant late infantile neuronal ceroid lipofuscinosis (NCL): UK research findings L. Metayer1 *, R.J. Brown1 , A.M. Winstone1 , L. Stellitano1 , C.M. Verity1 . 1 PIND Surveillance Group, Addenbrooke’s Hospital, Cambridge, United Kingdom Objective: To describe the presenting features and abnormalities found on investigation in two subgroups of NCL; late infantile (LINCL) and variant late infantile (VLINCL). Methods: Data from the British Paediatric Surveillance Unit (BPSU) study of children with suspected progressive intellectual and neurological deterioration (PIND) were analysed for children with LINCL or VLINCL who presented between January 1995 and December 2008. Results: 69 patients were identified (LINCL 57, VLINCL 12). Average age at referral; LINCL − 63 months and VLINCL − 71 months. Median age at first symptoms; LINCL − 36 months and VLINCL − 48 months. Clinical features evolved. The clinical presentation of LINCL included seizures (86%), developmental delay (79%), gait disturbance (37%) and behavioural change (28%) and then bulbar and visual problems developed. Initial reported seizure type varied, with myoclonic epilepsy dominating later.
Oral presentations For VLINCL the predominant presenting feature was developmental delay (92%), either global or regression. Later features were bulbar problems (50%), seizures (42%), visual loss (42%), gait (33%) and behavioural disturbance (25%). MRI brain imaging was abnormal in 77% of LINCL cases, with cerebral and/or cerebellar atrophy in 41/57. In VLINCL 6/7 MRIs were abnormal. Electrophysiological studies were less productive; reported EEG changes infrequently described occipital spikes (6/57) and a significant proportion had normal VEP (LINCL 14%, VLINCL 8%) and/or ERGs (LINCL 11%, VLINCL 8%). 29/30 LINCL patients were TPP1 (tripeptidyl-peptidase 1) deficient. 7 VLINCL were tested; all had normal TPP1 and PPT1 (palmitoyl protein thioesterase 1) levels. Genetic results: out of 22 LINCL patients, 21 had CLN2 mutations. 3 VLINCL had normal genetic analysis. Conclusions: This population-based study of children with neurodegenerative disorders provides helpful clinical information about LINCL. Enzyme and genetic analyses are becoming increasingly important. Acknowledgements: PIND is funded by the English Department of Health [121/6443]. O6-5 Aromatic L-amino acid decarboxylase (AADC) deficiency: the UK experience A.D. Gika1 *, S. Jones2 , T.J. Hedderly1,5 , S. Heales3 , M.P. Champion4 . 1 Paediatric Neurology, Evelina Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom; 2 Paediatric Inherited Metabolic Disease, Royal Manchester Children’s Hospital, Manchester, United Kingdom; 3 Institute of Neurology, National Hospital, University College Foundation Trust, London, United Kingdom; 4 Paediatric Metabolic Medicine, Evelina Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom; 5 Paediatric Neurology, King’s College Hospital NHS Foundation Trust, London, United Kingdom Objective: To report the UK experience on AADC deficiency. Methods: We reviewed the 4 patients from 3 unrelated families diagnosed with AADC deficiency in the UK retrospectively collecting data on clinical and biochemical characteristics, treatment and follow-up. Results: All patients are born to non-consanguinous Caucasian parents. Median age at AADC deficiency diagnosis was 21 months (range 7 months to 12 years). Patient 1 (boy, 11 years) presented aged 7 months with motor delay and irritability. Examination findings of fluctuating limb hypertonia and brisk reflexes led to a diagnosis of 4-limb motor disorder; later a dystonic component evolved while sleep disturbances and increased sweating were reported. Patients 2 (boy, 21 months) and 3 (girl, 21 months) presented aged 3 months with episodic dystonic/choreoathetoid movements on a background of hypotonia and bilateral ptosis. In all 3 patients some of the initial symptoms were attributed to gastrointestinal causes while in Patient 3 epilepsy and congenital myasthenia were considered. Symptom variability with improvement after sleep was reported in all 3. Patient 4 (boy, 12 years) was diagnosed with epilepsy aged 6 years; development was age-appropriate. Diagnosis was revisited following AADC deficiency diagnosis in his sister (Patient 3). On questioning excessive tiredness towards the end of the day and brief upward eye movements suggestive of minor oculogyric episodes were reported. Diagnosis was based on a suggestive cerebrospinal fluid neurotransmitter pattern (reduced HVA & 5-HIAA) and confirmed by enzymology. Patients were managed with pyridoxine or pyridoxal phosphate and a monoamine oxidase inhibitor with or without a dopamine agonist. Clinical response was variable.
Oral presentations Conclusions: AADC deficiency has a variable phenotype with regard to symptomatology and severity. Although rare, it may be under-diagnosed as mild cases exist and common conditions including cerebral palsy and epilepsy are differential diagnostic considerations. New advances in diagnosis and treatment may change management of patients with AADC deficiency in future. 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 . 1 Neuropediatrics, Necker Enfants Malades, Paris, France; 2 Metabolic Disease, Necker Enfants Malades, Paris, France; 3 Pediatric Radiology, Necker Enfants Malades, Paris, France; 4 Genetics, Necker Enfants Malades, Paris, France Among rare causes of neurovascular events in children, a few case reports of Ornithine TransCarbamylase (OTC) deficiency, a X-linked urea cycle deficiency, have been reported. Being a rare disease, epidemiological, clinical and radiological data are scarce about such events in children. Objective: To assess frequency, clinical and radiological features of child patients with OTC deficiency presenting with neurovascular events. Methods: We reviewed retrospectively charts of pediatric patients (<18 y) with OTC deficiency followed between 1974 and 2008 in a single pediatric referee center, and focused on children reported having a stroke or a stroke-like event. Brain CT-scans and MRI analysis were performed by the same pediatric neuroradiologist. Results: 100 charts were reviewed, 23 with neonatal onset (<28 days) and 77 with late-onset forms. Among them, 3 infants (2 girls, 1 boy) were reported having one or several stroke or stroke-like events at age ranging 7−20 months (3.8% of lateonset forms). Although all had previous chronic vomiting and psychomotor delay, these acute events revealed the disease. They presented with sudden hemiparesis contemporary to infectious episode or increased vomiting and seizures the following days. None of them presented with consciousness troubles. Ammoniemia checking revealed hyperammoniemia (190 358 mmol/L), driving to the enzymatic and molecular diagnosis of OTC deficiency. Brain MRI and CT-scans showed focal stroke-like (1 patient), multifocal successive stroke-like lesions (1 patient) or bilateral watershed zones cytotoxic lesions (1 patient). Conclusions: In our series, acute neurovascular events were not exceptional and lead to the diagnosis of late-onset forms of OTC deficiency in 3 infants. No child had typical arterial ischemic stroke. Stroke-like or watershed zones stroke events, especially in infants having chronic vomiting or psychomotor delay, should lead clinicians to metabolic investigations, including ammoniemia dosage.
S15
Session 7: Parallel free papers session Royal Hall 1 October 2009, 16.30 19.30 O7-1 Upper extremity function and occupational performance in spastic CP children following lower extremity botulinum toxin injection A. Fattal-Valevski1 *, T. Tal Keren-Capelovitch2 , T. Jarus3 . 1 Pediatric Neurology Unit, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; 2 Department of Occupational Therapy, Stanley Steyer School of Health Professions, Tel-Aviv University, Tel Aviv, Israel; 3 Department of Occupational Science and Occupational Therapy, University of British Columbia, Vancouver, Canada Objective: We studied the effect of Botulinum Toxin A (BTA) injections to the lower extremities of spastic CP children on upper limb body function, occupational performance, and parental satisfaction of performance in daily activities. Methods: Sixteen spastic CP children, aged 2−8 years, GMFCS levels I-IV, referred to a child neurology outpatient clinic for BTA injections to the lower limbs, underwent four assessments: one month prior to injection, immediate preinjection, and one and 5 to 6 months post injection. Three tools were used to test everyday function (COPM and PEDI) and upper extremity body function (QUEST). Results: Significant improvement was documented for COPM (p < 0.001), QUEST (p < 0.05)(Figure 1) and for PEDI (p < 0.05) in the self care and social skills domains, between the immediate preinjection and the two post injection assessments, indicating that improvement lasted for at least six months.
Figure 1. Conclusions: BTA injections to the lower extremities in CP children, improve upper limb body function and occupational performance. This constitutes significant implications for intervention strategies and tactics. O7-2 Cerebral palsy prevalence rates among normal birth weight or at term children during the past two decades in Europe E. Sellier1 *, G. Surman2 , K. Himmelmann3 , G. Andersen4 , C. Cans1 . 1ThEMAS − RHEOP, Public Health Department, CHU de Grenoble, France; 2 Child − National Perinatal Epidemiology Unit, University of Oxford, United Kingdom; 3The Queen Silvia Children’s Hospital/Sahlgrenska University Hospital, Goteborg, Sweden; ¨ 4 Habilitation Center, Vestfold Hospital, Tonsberg, Norway Objectives: Cerebral palsy (CP) is the most common cause of severe physical disability in children and half of children with
Oral presentations For VLINCL the predominant presenting feature was developmental delay (92%), either global or regression. Later features were bulbar problems (50%), seizures (42%), visual loss (42%), gait (33%) and behavioural disturbance (25%). MRI brain imaging was abnormal in 77% of LINCL cases, with cerebral and/or cerebellar atrophy in 41/57. In VLINCL 6/7 MRIs were abnormal. Electrophysiological studies were less productive; reported EEG changes infrequently described occipital spikes (6/57) and a significant proportion had normal VEP (LINCL 14%, VLINCL 8%) and/or ERGs (LINCL 11%, VLINCL 8%). 29/30 LINCL patients were TPP1 (tripeptidyl-peptidase 1) deficient. 7 VLINCL were tested; all had normal TPP1 and PPT1 (palmitoyl protein thioesterase 1) levels. Genetic results: out of 22 LINCL patients, 21 had CLN2 mutations. 3 VLINCL had normal genetic analysis. Conclusions: This population-based study of children with neurodegenerative disorders provides helpful clinical information about LINCL. Enzyme and genetic analyses are becoming increasingly important. Acknowledgements: PIND is funded by the English Department of Health [121/6443]. O6-5 Aromatic L-amino acid decarboxylase (AADC) deficiency: the UK experience A.D. Gika1 *, S. Jones2 , T.J. Hedderly1,5 , S. Heales3 , M.P. Champion4 . 1 Paediatric Neurology, Evelina Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom; 2 Paediatric Inherited Metabolic Disease, Royal Manchester Children’s Hospital, Manchester, United Kingdom; 3 Institute of Neurology, National Hospital, University College Foundation Trust, London, United Kingdom; 4 Paediatric Metabolic Medicine, Evelina Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom; 5 Paediatric Neurology, King’s College Hospital NHS Foundation Trust, London, United Kingdom Objective: To report the UK experience on AADC deficiency. Methods: We reviewed the 4 patients from 3 unrelated families diagnosed with AADC deficiency in the UK retrospectively collecting data on clinical and biochemical characteristics, treatment and follow-up. Results: All patients are born to non-consanguinous Caucasian parents. Median age at AADC deficiency diagnosis was 21 months (range 7 months to 12 years). Patient 1 (boy, 11 years) presented aged 7 months with motor delay and irritability. Examination findings of fluctuating limb hypertonia and brisk reflexes led to a diagnosis of 4-limb motor disorder; later a dystonic component evolved while sleep disturbances and increased sweating were reported. Patients 2 (boy, 21 months) and 3 (girl, 21 months) presented aged 3 months with episodic dystonic/choreoathetoid movements on a background of hypotonia and bilateral ptosis. In all 3 patients some of the initial symptoms were attributed to gastrointestinal causes while in Patient 3 epilepsy and congenital myasthenia were considered. Symptom variability with improvement after sleep was reported in all 3. Patient 4 (boy, 12 years) was diagnosed with epilepsy aged 6 years; development was age-appropriate. Diagnosis was revisited following AADC deficiency diagnosis in his sister (Patient 3). On questioning excessive tiredness towards the end of the day and brief upward eye movements suggestive of minor oculogyric episodes were reported. Diagnosis was based on a suggestive cerebrospinal fluid neurotransmitter pattern (reduced HVA & 5-HIAA) and confirmed by enzymology. Patients were managed with pyridoxine or pyridoxal phosphate and a monoamine oxidase inhibitor with or without a dopamine agonist. Clinical response was variable.
Oral presentations Conclusions: AADC deficiency has a variable phenotype with regard to symptomatology and severity. Although rare, it may be under-diagnosed as mild cases exist and common conditions including cerebral palsy and epilepsy are differential diagnostic considerations. New advances in diagnosis and treatment may change management of patients with AADC deficiency in future. 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 . 1 Neuropediatrics, Necker Enfants Malades, Paris, France; 2 Metabolic Disease, Necker Enfants Malades, Paris, France; 3 Pediatric Radiology, Necker Enfants Malades, Paris, France; 4 Genetics, Necker Enfants Malades, Paris, France Among rare causes of neurovascular events in children, a few case reports of Ornithine TransCarbamylase (OTC) deficiency, a X-linked urea cycle deficiency, have been reported. Being a rare disease, epidemiological, clinical and radiological data are scarce about such events in children. Objective: To assess frequency, clinical and radiological features of child patients with OTC deficiency presenting with neurovascular events. Methods: We reviewed retrospectively charts of pediatric patients (<18 y) with OTC deficiency followed between 1974 and 2008 in a single pediatric referee center, and focused on children reported having a stroke or a stroke-like event. Brain CT-scans and MRI analysis were performed by the same pediatric neuroradiologist. Results: 100 charts were reviewed, 23 with neonatal onset (<28 days) and 77 with late-onset forms. Among them, 3 infants (2 girls, 1 boy) were reported having one or several stroke or stroke-like events at age ranging 7−20 months (3.8% of lateonset forms). Although all had previous chronic vomiting and psychomotor delay, these acute events revealed the disease. They presented with sudden hemiparesis contemporary to infectious episode or increased vomiting and seizures the following days. None of them presented with consciousness troubles. Ammoniemia checking revealed hyperammoniemia (190 358 mmol/L), driving to the enzymatic and molecular diagnosis of OTC deficiency. Brain MRI and CT-scans showed focal stroke-like (1 patient), multifocal successive stroke-like lesions (1 patient) or bilateral watershed zones cytotoxic lesions (1 patient). Conclusions: In our series, acute neurovascular events were not exceptional and lead to the diagnosis of late-onset forms of OTC deficiency in 3 infants. No child had typical arterial ischemic stroke. Stroke-like or watershed zones stroke events, especially in infants having chronic vomiting or psychomotor delay, should lead clinicians to metabolic investigations, including ammoniemia dosage.
S15
Session 7: Parallel free papers session Royal Hall 1 October 2009, 16.30 19.30 O7-1 Upper extremity function and occupational performance in spastic CP children following lower extremity botulinum toxin injection A. Fattal-Valevski1 *, T. Tal Keren-Capelovitch2 , T. Jarus3 . 1 Pediatric Neurology Unit, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; 2 Department of Occupational Therapy, Stanley Steyer School of Health Professions, Tel-Aviv University, Tel Aviv, Israel; 3 Department of Occupational Science and Occupational Therapy, University of British Columbia, Vancouver, Canada Objective: We studied the effect of Botulinum Toxin A (BTA) injections to the lower extremities of spastic CP children on upper limb body function, occupational performance, and parental satisfaction of performance in daily activities. Methods: Sixteen spastic CP children, aged 2−8 years, GMFCS levels I-IV, referred to a child neurology outpatient clinic for BTA injections to the lower limbs, underwent four assessments: one month prior to injection, immediate preinjection, and one and 5 to 6 months post injection. Three tools were used to test everyday function (COPM and PEDI) and upper extremity body function (QUEST). Results: Significant improvement was documented for COPM (p < 0.001), QUEST (p < 0.05)(Figure 1) and for PEDI (p < 0.05) in the self care and social skills domains, between the immediate preinjection and the two post injection assessments, indicating that improvement lasted for at least six months.
Figure 1. Conclusions: BTA injections to the lower extremities in CP children, improve upper limb body function and occupational performance. This constitutes significant implications for intervention strategies and tactics. O7-2 Cerebral palsy prevalence rates among normal birth weight or at term children during the past two decades in Europe E. Sellier1 *, G. Surman2 , K. Himmelmann3 , G. Andersen4 , C. Cans1 . 1ThEMAS − RHEOP, Public Health Department, CHU de Grenoble, France; 2 Child − National Perinatal Epidemiology Unit, University of Oxford, United Kingdom; 3The Queen Silvia Children’s Hospital/Sahlgrenska University Hospital, Goteborg, Sweden; ¨ 4 Habilitation Center, Vestfold Hospital, Tonsberg, Norway Objectives: Cerebral palsy (CP) is the most common cause of severe physical disability in children and half of children with