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P267 – 2147 Maternal hyperphenylalaninemia
E U R O P E A N JO U R N A L O F PAEDIATRIC N E U R O L O G Y
der and should be excluded in young children with oculogyric crises.
P267 - 2147 Maternal hyperphenylalaninemia Yüksel D, Özel A, Okur I, Aksoy A, Ozkan M, Gunduz M. Dr. Sami Ulus Children’s Health and Diseases Training and Research Hospital, Ankara, Turkey – [email protected] Untreated maternal phenylketonuria/hyperphenylalaninemia is an embryopathy which may result in nonphenylketonuric offspring with neonatal sequelae, especially intellectual disability, microcephaly, low birth weight and congenital heart disease. Dietary treatment to control phenylalanine concentrations can prevent these sequelae. This report present the case two brothers both diagnosed as maternal hyperphenylalaninemia who referred to our clinic because of microcephaly, neuromotor delay and epilepsy. Three and five years old boys were born to consanguinity parents who were second degree cousins. Perinatal history was insignificant. Physical examination both revealed head circumference below 3rd percentile, coarse face, cortical fisting, and increased deep tendon reflexes. Five years old patient was spastic quadriplegic. Analysis of urine and blood aminoacids, urine organic acids, tandem mass spectrometry, and lysososmal enzymes were normal. Magnetic resonance imaging of the brain showed enlargement of lateral and third ventricules, thinning of corpus callosum, and periventricular white matter volume loss on both brothers. Serum aminoacid analysis of mother disclosed elevated phenylalanine level (359.1 μmol/L (21–150 mmol/L)) cleared the diagnosis of maternal hyperphenyalaninemia. It’s important to treat hyperphenylalaninemia to prevent pregnancy complications and embryopathy and undiagnosed women with hyperphenylalaninemia, unknowingly at risk for producing offspring with maternal phenylketonuria embryopathy.
P268 - 2073 Very long-chain fatty acids in patients with various central nervous system disorders Stradomska TJ, Jamroz E, Paprocka J, Syczewska M. Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children’s Memorial Health Institute, Warsaw, Poland – [email protected] Background: Very long-chain fatty acids (VLCFA; >C22:0; C24:0, C26:0) incorporated in lipid. compounds forming structure of the nervous system. Degradation of VLCFA are placed exclusively in peroxisomes. Detection of increased VLCFA levels in blood is a key biomarker for peroxisomal diseases, manifested by severe neurological signs (demyelination, epilepsy). Purpose: The aim of the study was to examine serum VLCFA in patients in developmental age with various central nervous system disorders. Methods and patients: Serum VLCFA was examined in 50 children (35 males and 15 females) aged from 2 months to 9 years. The children were diagnosed with refractory epilepsy N=21 (refractory symptomatic epilepsy: N=18, refractory epilepsy of unknown etiology: N=3), congenital brain abnormalities (N=12), developmental delay N=11, progressive encephalopathy N=4, cerebral palsy N=2. Serum VLCFA levels was detected by gas chromatography method. Results: The data show increased C24:0/C22:0 ratio and decreased C22:0 concentration in comparison to normal values at significant levels in investigated group.
17s (2013) S1 – S149
S127
P269 - 2062 Phenotypic variability in x linked adrenoleukodystrophy through clinic experience Pomeran C, Tarta O, Motoescu C, Burloiu C, Barca D, Craiu D. “Prof. Dr. Al. Obregia” Hospital, Clinic of Pediatric Neurology, Bucharest, Romania – [email protected] Motivation: X linked adrenoleucodystrophy (XALD) is a peroxisomal disorder caused by accumulation of very long chain fatty acids in plasma and various tissues. The most affected organs are cerebral white matter, adrenals and testis. The disease results from inactivating mutations on ABCD1 gene, located on Xp28 chromosome. The only effective treatment are bone marrow transplantation, during the pre-symptomatic phase of the disease, and just recently, hematopoietic stem cells gene therapy. Early diagnosis is essential for the possible therapeutic interventions. Objectives: To highlight the phenotypic variability among patients diagnosed with XALD. Material: Our case-study refers to a group of 8 patients diagnosed in our clinic for XALD during the last 5 years. Patients are 4 to 15 years old males at first presentation. Two patients are brothers, but the rest of them are unrelated. For all of them, the XALD diagnosis has been assessed in terms of clinical manifestations, biochemical features, magnetic resonance imaging (MRI) and spectroscopy (MRS) results. Personal and family history records have been also considered. Based on our observations and some correlations with the current literature we have succeeded to emphasize some connections between MRI/MRS findings and the clinical course of the disease. Conclusions: Only one patient was diagnosed in the pre-symptomatic phase. For all the others, bone marrow transplantation was not an option. All patients have had the onset of symptoms at the ages between 4 to 9 years. Five patients were diagnosed with adrenal insufficiency. One of them associated IGF1 deficiency, and also extensive cerebral calcifications. Another patient had familial phenotypic variability. For all our patients we found the same correlation between MRI findings and clinical course as currently accepted in the literature. The group exhibited a variety of clinical, biochemical and imagistic features. Some unusual biochemical, imagistic and familial peculiarities have been also revealed.
P270 - 2046 Therapeutic effects in tardive phase of cerebral folate deficiency Tarta-Arsene O, Moisa G, Leanca M, Avram P, Tabacaru R, Craiu M. Pediatric Neurology Department, Clinical Hospital ’Al Obregia’, Bucharest, Romania – [email protected] Purpose: Cerebral folate deficiency is a progressive neurological disease associated with low cerebrospinal fluid 5methyltetrahydrofolate in the presence of normal folate metabolism outside the nervous system. The authors will present the clinical response of therapy after 11 years of evolution of the disease. Methods and results: Anton is a 18 years old boy, with gradual onset of a diskinetic movements from the age of 7, initially as postural tremor of the left upper limb, then as generalized tremor. The movement disorder was progressive, so at the age of 17, he had a combined abnormal movements as truncal dystonia and asymmetric chorea of the limbs. The cerebral MRI was normal. It was excluded: Wilson disease, systemic lupus eritematous, chronic exposure to toxics, infectious disease. Analysis of CSF showed deficiency of cerebral folate. After the anesthesia for cerebral MRI, he developed an acute respiratory deficiency and he needed oro-tracheal intubation and artificial ventilation. At that moment, he started treatment with folic acid, first intravenously, than orally, with semnificative clinical improvement from the first day (decreasing of amplitude and frequency of diskinetic movements). In the present time, after 12 months he is at home with motor autonomy with slight diski-
der and should be excluded in young children with oculogyric crises.
P267 - 2147 Maternal hyperphenylalaninemia Yüksel D, Özel A, Okur I, Aksoy A, Ozkan M, Gunduz M. Dr. Sami Ulus Children’s Health and Diseases Training and Research Hospital, Ankara, Turkey – [email protected] Untreated maternal phenylketonuria/hyperphenylalaninemia is an embryopathy which may result in nonphenylketonuric offspring with neonatal sequelae, especially intellectual disability, microcephaly, low birth weight and congenital heart disease. Dietary treatment to control phenylalanine concentrations can prevent these sequelae. This report present the case two brothers both diagnosed as maternal hyperphenylalaninemia who referred to our clinic because of microcephaly, neuromotor delay and epilepsy. Three and five years old boys were born to consanguinity parents who were second degree cousins. Perinatal history was insignificant. Physical examination both revealed head circumference below 3rd percentile, coarse face, cortical fisting, and increased deep tendon reflexes. Five years old patient was spastic quadriplegic. Analysis of urine and blood aminoacids, urine organic acids, tandem mass spectrometry, and lysososmal enzymes were normal. Magnetic resonance imaging of the brain showed enlargement of lateral and third ventricules, thinning of corpus callosum, and periventricular white matter volume loss on both brothers. Serum aminoacid analysis of mother disclosed elevated phenylalanine level (359.1 μmol/L (21–150 mmol/L)) cleared the diagnosis of maternal hyperphenyalaninemia. It’s important to treat hyperphenylalaninemia to prevent pregnancy complications and embryopathy and undiagnosed women with hyperphenylalaninemia, unknowingly at risk for producing offspring with maternal phenylketonuria embryopathy.
P268 - 2073 Very long-chain fatty acids in patients with various central nervous system disorders Stradomska TJ, Jamroz E, Paprocka J, Syczewska M. Department of Biochemistry, Radioimmunology and Experimental Medicine, The Children’s Memorial Health Institute, Warsaw, Poland – [email protected] Background: Very long-chain fatty acids (VLCFA; >C22:0; C24:0, C26:0) incorporated in lipid. compounds forming structure of the nervous system. Degradation of VLCFA are placed exclusively in peroxisomes. Detection of increased VLCFA levels in blood is a key biomarker for peroxisomal diseases, manifested by severe neurological signs (demyelination, epilepsy). Purpose: The aim of the study was to examine serum VLCFA in patients in developmental age with various central nervous system disorders. Methods and patients: Serum VLCFA was examined in 50 children (35 males and 15 females) aged from 2 months to 9 years. The children were diagnosed with refractory epilepsy N=21 (refractory symptomatic epilepsy: N=18, refractory epilepsy of unknown etiology: N=3), congenital brain abnormalities (N=12), developmental delay N=11, progressive encephalopathy N=4, cerebral palsy N=2. Serum VLCFA levels was detected by gas chromatography method. Results: The data show increased C24:0/C22:0 ratio and decreased C22:0 concentration in comparison to normal values at significant levels in investigated group.
17s (2013) S1 – S149
S127
P269 - 2062 Phenotypic variability in x linked adrenoleukodystrophy through clinic experience Pomeran C, Tarta O, Motoescu C, Burloiu C, Barca D, Craiu D. “Prof. Dr. Al. Obregia” Hospital, Clinic of Pediatric Neurology, Bucharest, Romania – [email protected] Motivation: X linked adrenoleucodystrophy (XALD) is a peroxisomal disorder caused by accumulation of very long chain fatty acids in plasma and various tissues. The most affected organs are cerebral white matter, adrenals and testis. The disease results from inactivating mutations on ABCD1 gene, located on Xp28 chromosome. The only effective treatment are bone marrow transplantation, during the pre-symptomatic phase of the disease, and just recently, hematopoietic stem cells gene therapy. Early diagnosis is essential for the possible therapeutic interventions. Objectives: To highlight the phenotypic variability among patients diagnosed with XALD. Material: Our case-study refers to a group of 8 patients diagnosed in our clinic for XALD during the last 5 years. Patients are 4 to 15 years old males at first presentation. Two patients are brothers, but the rest of them are unrelated. For all of them, the XALD diagnosis has been assessed in terms of clinical manifestations, biochemical features, magnetic resonance imaging (MRI) and spectroscopy (MRS) results. Personal and family history records have been also considered. Based on our observations and some correlations with the current literature we have succeeded to emphasize some connections between MRI/MRS findings and the clinical course of the disease. Conclusions: Only one patient was diagnosed in the pre-symptomatic phase. For all the others, bone marrow transplantation was not an option. All patients have had the onset of symptoms at the ages between 4 to 9 years. Five patients were diagnosed with adrenal insufficiency. One of them associated IGF1 deficiency, and also extensive cerebral calcifications. Another patient had familial phenotypic variability. For all our patients we found the same correlation between MRI findings and clinical course as currently accepted in the literature. The group exhibited a variety of clinical, biochemical and imagistic features. Some unusual biochemical, imagistic and familial peculiarities have been also revealed.
P270 - 2046 Therapeutic effects in tardive phase of cerebral folate deficiency Tarta-Arsene O, Moisa G, Leanca M, Avram P, Tabacaru R, Craiu M. Pediatric Neurology Department, Clinical Hospital ’Al Obregia’, Bucharest, Romania – [email protected] Purpose: Cerebral folate deficiency is a progressive neurological disease associated with low cerebrospinal fluid 5methyltetrahydrofolate in the presence of normal folate metabolism outside the nervous system. The authors will present the clinical response of therapy after 11 years of evolution of the disease. Methods and results: Anton is a 18 years old boy, with gradual onset of a diskinetic movements from the age of 7, initially as postural tremor of the left upper limb, then as generalized tremor. The movement disorder was progressive, so at the age of 17, he had a combined abnormal movements as truncal dystonia and asymmetric chorea of the limbs. The cerebral MRI was normal. It was excluded: Wilson disease, systemic lupus eritematous, chronic exposure to toxics, infectious disease. Analysis of CSF showed deficiency of cerebral folate. After the anesthesia for cerebral MRI, he developed an acute respiratory deficiency and he needed oro-tracheal intubation and artificial ventilation. At that moment, he started treatment with folic acid, first intravenously, than orally, with semnificative clinical improvement from the first day (decreasing of amplitude and frequency of diskinetic movements). In the present time, after 12 months he is at home with motor autonomy with slight diski-