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MLP09 Evaluation of central nervous system in patients with glycogen storage disease type Ia
Abstracts: Poster Presentations, the Seventh European Paediatric Neurology Society (EPNS) Congress MLP08 Developmental delay and cerebral palsy associated with tryptophan hydroxylase deficiency F. Langius1 *, N. Abeling2 , M. Duran2 , B.T. Poll-The3 . Department of Pediatrics, St Lucas Andreas Hospital, 2 Departments of Clinical Chemistry and Pediatrics, 3 Department of Child Neurology, Academic Medical Centre, Amsterdam, The Netherlands 1
We present a 12-year-old boy of unrelated parents. Delivery was complicated by umbilical cord strangulation. He developed cerebral palsy and his psychomotor development was strikingly retarded. A cerebral MRI was not indicative for perinatal asphyxia as the causative factor for the clinical problems. At the age of seven, he developed epilepsy and anticonvulsant therapy was started. From the age of 10 a progressive motor restlessness and uncontrolled yelling resembling Tourette syndrome was noticed. This prompted investigation of neurotransmitters in the CSF, after all previous metabolic investigations were negative. Low levels of 5-hydroxyindoleacetic acid (36 nmol/l; ref. 68 115) as well as its precursor 5-hydroxytryptophan (4 nmol/l; ref. 5.2−7.8) were found. As the other aromatic neurotransmitter metabolites were normal, the possibility of isolated tryptophan hydroxylase (TPH) deficiency was raised. Mutation analysis will be performed. Subsequent treatment with 5-hydroxytryptophan resulted in a marked biochemical and some clinical improvement as yet. The clinical condition of our patient clearly differs from previously reported patients with presumed TPH deficiency, but nevertheless the possibly beneficial effect of treatment is intriguing and warrants further investigations, particularly in view of the scarce knowledge about the clinical phenotype of this neurotransmitter defect. MLP09 Evaluation of central nervous system in patients with glycogen storage disease type Ia F. Gurakan1 , Y. Aydemir1 , A. Yuce1 , I.S. Temizel1 , H. Demir1 , D. Yalnizoglu2 *, M. Topcu2 , Y. Usta1 , E. Erdogan2 , H. Ozen1 , B. Erbas3 , E. Lay3 . 1 Dept of Pediatric Gastroenterology, Hepatology and Nutrition, 2 Dept of Pediatric Neurology, 3 Dept of Nuclear Medicine, Hacettepe University, Ankara, Turkey Rationale: Metabolic abnormalities secondary to fasting hypoglycemia may affect central nervous system (CNS) as well as other organs in patients with glycogen storage disease type I a (GSDIa). We studied neurological outcome in patients with GSDIa. Materials and Methods: 23 patients with GSDIa (age 1.3−17 y, mean 9.1±4.1 y, 78.3% males) were evaluated after a mean follow up of 6.8±4.2 y (range 3 m-15 y). All had normal neurological examination. Evoked potentials (VEP in 21, BAEP in 20 patients), EEG (18 patients), and MRI (15 patients) were obtained. Psychometric evaluation was performed in 15 patients. Results: VEP showed delayed P1 latancies bilaterally in five and unilaterally in two patients. BAEP showed increased I-V interpeak latancies in two patients. EEG showed epileptiform abnormality one patient, and non-epileptiform abnormalities in nine. MRI revealed white matter changes in 5 patients. Two patients had borderline IQ, five were dull-normal, and 3 had mild mental retardation. When patients were divided into two groups according to good vs poor metabolic control, patients with poor control had more frequent abnormal results. Overall 20/23 patients had at least one abnormal result. Conclusion: GSDIa patients, especially those with poor metabolic control seem to have increased risk for subclinical CNS involvement.
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MLP010 Pompe disease: early signs of benefit in a child with late-onset form following treatment with enzyme replacement therapy (ERT) D. Lianou1 *, D. Syrengelas2 , P. Poulopoulos1 , K. Kotsonis1 , A. Klimentopoulou1 , I. Mavridou3 , H. Michelakakis3 , K. Kassiou1 . 1 1st Pediatric Department, 2 Department of Pediatric Physical Therapy, “Aghia Sophia” Childrens’ Hospital, 3 Enzymology and Cellular Function, Institute of Child Health, Athens, Greece Background: Pompe disease (PD) is an autosomal recessive storage disease caused by acid a-glucocidase deficiency and characterized by lysosomal accumulation of glycogen, leading to progressive muscle weakness. Objective: To present the short-term results of ERT in a patient with juvenile-onset PD following 10 months of treatment. Patient and Methods: The patient, a 13 year-old boy, manifested a clinically overt proximal myopathy at 8 years. ERT (MyozymeTM 20 mg/kgr qow) was initiated 10 months ago. Muscle strength and function were evaluated using MRC scale/HHD and GMFM, respectively and pulmonary function with spirometry. Results: At baseline, the patient had mild limitations in motor performance, mainly of the lower extremities, and suboptimal pulmonary function tests (FVC 76% of predicted). Following the first 10 months of treatment a subtle improvement of skeletal muscle strength and function was noted. The GMFM score (dimension E: walking, running, jumping) improved from 95.83 to 98.61% and the HHD score increased from 1262 to 1404 Newton. The patient had stabilized pulmonary function, and remained free of pulmonary infections throughout the course of treatment. No infusion-associated reactions were observed. Conclusion: ERT is safe and appears to have therapeutic effect in late-oncet PD in terms of skeletal muscle strength and function. MLP011 Pompe disease: clinical trial with enzyme replacement therapy case presentation L. Selim *, Z. Seliem, A. Mancy. Specialised Cairo University Children Hospital, Cairo, Egypt Pompe disease is an autosomal recessive disorder caused by deficiency of the enzyme acid alpha glucosidase (GAA) which result in intralysosomal accumulation of glycogen in multiple organs with prominent involvement of heart and skeletal muscles. The clinical presentation is heterogeneous, largely due to the residual enzyme activity associated with different mutations in the GAA gene, thus it encompasses a range of phenotypes, all of which include varying degrees of myopathy but differ with respect to age of onset, extent of organ involvement and rate of progression to death. The most severe form is the classical infantile_onset disease, described by pompe with hypertrophic cardiomyopathy, hypotonia, hepatomegaly and death due to cardiorespiratory failure. At the other extreme is a slowly progressive proximal myopathic adult onset disease with involvement of skeletal muscle only. Ongoing clinical trials with enzyme replacement therapy have shown that enzyme replacement therapy (ERT) decreases cardiomegaly, and improve cardiac and skeletal muscle functions, thus offering hope for patients suffering from this lethal disorder. In this presentation, we will demonstrate the effect of enzyme replacement therapy with acid alpha glucosidase administered to one patient diagnosed as infantile pompe disease on both the cardiac and skeletal muscles functions with video demonstration.
We present a 12-year-old boy of unrelated parents. Delivery was complicated by umbilical cord strangulation. He developed cerebral palsy and his psychomotor development was strikingly retarded. A cerebral MRI was not indicative for perinatal asphyxia as the causative factor for the clinical problems. At the age of seven, he developed epilepsy and anticonvulsant therapy was started. From the age of 10 a progressive motor restlessness and uncontrolled yelling resembling Tourette syndrome was noticed. This prompted investigation of neurotransmitters in the CSF, after all previous metabolic investigations were negative. Low levels of 5-hydroxyindoleacetic acid (36 nmol/l; ref. 68 115) as well as its precursor 5-hydroxytryptophan (4 nmol/l; ref. 5.2−7.8) were found. As the other aromatic neurotransmitter metabolites were normal, the possibility of isolated tryptophan hydroxylase (TPH) deficiency was raised. Mutation analysis will be performed. Subsequent treatment with 5-hydroxytryptophan resulted in a marked biochemical and some clinical improvement as yet. The clinical condition of our patient clearly differs from previously reported patients with presumed TPH deficiency, but nevertheless the possibly beneficial effect of treatment is intriguing and warrants further investigations, particularly in view of the scarce knowledge about the clinical phenotype of this neurotransmitter defect. MLP09 Evaluation of central nervous system in patients with glycogen storage disease type Ia F. Gurakan1 , Y. Aydemir1 , A. Yuce1 , I.S. Temizel1 , H. Demir1 , D. Yalnizoglu2 *, M. Topcu2 , Y. Usta1 , E. Erdogan2 , H. Ozen1 , B. Erbas3 , E. Lay3 . 1 Dept of Pediatric Gastroenterology, Hepatology and Nutrition, 2 Dept of Pediatric Neurology, 3 Dept of Nuclear Medicine, Hacettepe University, Ankara, Turkey Rationale: Metabolic abnormalities secondary to fasting hypoglycemia may affect central nervous system (CNS) as well as other organs in patients with glycogen storage disease type I a (GSDIa). We studied neurological outcome in patients with GSDIa. Materials and Methods: 23 patients with GSDIa (age 1.3−17 y, mean 9.1±4.1 y, 78.3% males) were evaluated after a mean follow up of 6.8±4.2 y (range 3 m-15 y). All had normal neurological examination. Evoked potentials (VEP in 21, BAEP in 20 patients), EEG (18 patients), and MRI (15 patients) were obtained. Psychometric evaluation was performed in 15 patients. Results: VEP showed delayed P1 latancies bilaterally in five and unilaterally in two patients. BAEP showed increased I-V interpeak latancies in two patients. EEG showed epileptiform abnormality one patient, and non-epileptiform abnormalities in nine. MRI revealed white matter changes in 5 patients. Two patients had borderline IQ, five were dull-normal, and 3 had mild mental retardation. When patients were divided into two groups according to good vs poor metabolic control, patients with poor control had more frequent abnormal results. Overall 20/23 patients had at least one abnormal result. Conclusion: GSDIa patients, especially those with poor metabolic control seem to have increased risk for subclinical CNS involvement.
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MLP010 Pompe disease: early signs of benefit in a child with late-onset form following treatment with enzyme replacement therapy (ERT) D. Lianou1 *, D. Syrengelas2 , P. Poulopoulos1 , K. Kotsonis1 , A. Klimentopoulou1 , I. Mavridou3 , H. Michelakakis3 , K. Kassiou1 . 1 1st Pediatric Department, 2 Department of Pediatric Physical Therapy, “Aghia Sophia” Childrens’ Hospital, 3 Enzymology and Cellular Function, Institute of Child Health, Athens, Greece Background: Pompe disease (PD) is an autosomal recessive storage disease caused by acid a-glucocidase deficiency and characterized by lysosomal accumulation of glycogen, leading to progressive muscle weakness. Objective: To present the short-term results of ERT in a patient with juvenile-onset PD following 10 months of treatment. Patient and Methods: The patient, a 13 year-old boy, manifested a clinically overt proximal myopathy at 8 years. ERT (MyozymeTM 20 mg/kgr qow) was initiated 10 months ago. Muscle strength and function were evaluated using MRC scale/HHD and GMFM, respectively and pulmonary function with spirometry. Results: At baseline, the patient had mild limitations in motor performance, mainly of the lower extremities, and suboptimal pulmonary function tests (FVC 76% of predicted). Following the first 10 months of treatment a subtle improvement of skeletal muscle strength and function was noted. The GMFM score (dimension E: walking, running, jumping) improved from 95.83 to 98.61% and the HHD score increased from 1262 to 1404 Newton. The patient had stabilized pulmonary function, and remained free of pulmonary infections throughout the course of treatment. No infusion-associated reactions were observed. Conclusion: ERT is safe and appears to have therapeutic effect in late-oncet PD in terms of skeletal muscle strength and function. MLP011 Pompe disease: clinical trial with enzyme replacement therapy case presentation L. Selim *, Z. Seliem, A. Mancy. Specialised Cairo University Children Hospital, Cairo, Egypt Pompe disease is an autosomal recessive disorder caused by deficiency of the enzyme acid alpha glucosidase (GAA) which result in intralysosomal accumulation of glycogen in multiple organs with prominent involvement of heart and skeletal muscles. The clinical presentation is heterogeneous, largely due to the residual enzyme activity associated with different mutations in the GAA gene, thus it encompasses a range of phenotypes, all of which include varying degrees of myopathy but differ with respect to age of onset, extent of organ involvement and rate of progression to death. The most severe form is the classical infantile_onset disease, described by pompe with hypertrophic cardiomyopathy, hypotonia, hepatomegaly and death due to cardiorespiratory failure. At the other extreme is a slowly progressive proximal myopathic adult onset disease with involvement of skeletal muscle only. Ongoing clinical trials with enzyme replacement therapy have shown that enzyme replacement therapy (ERT) decreases cardiomegaly, and improve cardiac and skeletal muscle functions, thus offering hope for patients suffering from this lethal disorder. In this presentation, we will demonstrate the effect of enzyme replacement therapy with acid alpha glucosidase administered to one patient diagnosed as infantile pompe disease on both the cardiac and skeletal muscles functions with video demonstration.