- Email: [email protected]
Clinical cases about uncommon genotype of congenital disorders of glycosylation
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 1 ( 2 0 1 7 ) e 1 2 3 ee 1 4 0
processing started by correcting for eddy current distortions and head motion using FMRIB's Diffusion Toolbox. FA, RD and MD maps for each patient and control were calculated using the eigenvalues extracted from the diffusion tensors. Results: PKU patients showed decreased MD values as compared with controls in the body and splenium of the corpus callosum, superior longitudinal fasciculus and in the corona radiata. RD values followed a very similar pattern, although decreased RD values were also found in the posterior limb of the internal capsule. FA values showed no significant differences between groups. Decreased MD values within the body of the corpus callosum significantly correlated negatively with age (r ¼ 0.77, p < 0.001) and concurrent phenylalanine values (r ¼ 0.76, p < 0.001). RD values in the body of the corpus callosum also significantly and negatively correlated with age (r ¼ 0.73, p < 0.002). Conclusions: WM abnormalities were present even in early treated PKU. Decreased MD values correlated significantly with concurrent Phe levels.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1048 P2-133 Hunter and fragile-X syndromes in a family with Xq27.3-q28 deletion that involves FMR1 and IDS genes S. Aguilera-Albesa, A. Mosquera-Gorostidi, I. Naberan-Mardaras, N. Gorria-Redondo, I. Urriza-Ripa, M.E. Yoldi-Petri, M.A. Ramos-Arroyo, M.J. Coll, E. Aznal, F. Sanchez-Valverde. Complejo Hospitalario de Navarra, Navarrabiomed, Pamplona, Spain Objective: To describe the different clinical presentation and outcome of a brother and a sister, carrying the same deletion involving FMR1 and IDS genes. Methods: Family case description. Results: The brother presented at 6-mo with psychomotor delay, macrosomia, mild umbilical hernia and no dysmorphic features. At 10-month-old he suffered a hemi- convulsive status. Then cerebral MRI revealed leukoencephalopathy with corpus callosum cysts. Additional investigations showed mild hepatomegaly, increased excretion of heparan and dermatan sulphate bands, and a nearly undetectable activity of iduronate-2-sulfatase enzyme in leukocytes. Molecular studies revealed a Xq27.3- q28 deletion involving FMR1 and IDS genes. He started enzymatic replacement therapy with idursulfase from 12-mo. At 3-yo, anthropometric values were >P97 but decreased afterwards. Coarse facial features appeared progressively together with a carpal tunnel syndrome that required surgery at 3-yo. At 6-yo he presents severe global psychomotor delay with no expressive language, walking with support, joints deformations and repetitive motor and self-injury behaviours. Urine excretion of glycosaminoglycans remains reduced by 50%. The sister carried the same deletion, confirmed prenatally. She presented with postnatal macrosomia, sparse hair growth in fronto-temporal regions and developmental delay. She walks independently from 24mo but expressive language is not present at 3-yo, with extreme shyness. Her cerebral MRI and urine excretion of glycosaminoglycans are normal. The mother carried the same deletion but she is asymptomatic. Enzymatic and skewed patterns studies in the sister and mother are on course. Conclusion: The coexistence of Hunter and Fragile-X syndromes is rare. In a boy with a deletion affecting both IDS and FMR1 genes, the diagnosis of mucopolysaccharidosis may be delayed by a more prominent neurological presentation in the absence of systemic features during the first year of life. In this case, the neuroimaging provided an earlier diagnosis.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1049
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P2-134 Spastic paraplegia with crystalline retinopathy: A recognisable phenotype? Patrick Verloo, Patricia Delbeke, Rudy Van Coster. Department of Paediatrics, Division of Paediatric Neurology, Ghent University Hospital, Ghent, Belgium Objective: Genetic diagnosis of hereditary spastic paraparesis (HSP) is often challenging because of lack of typical clinical or biochemical abnormalities. Case: An eight year old girl presented at the consultation with severe spastic paraparesis which had developed slowly over the last two years. More recently, a tremor in the hand became apparent. Perinatal history was unremarkable and early milestones were reached within normal limits. Cognitive functioning was normal. Dysmorphic features and skin lesions were not seen. Cerebral MRI and MRI of the spine were normal. Work-up was done for hereditary spastic paraparesis. Results: Fundoscopy showed a crystalline retinopathy as is typically seen in € gren-Larsson syndrome. As ichtyosis was absent in this patient Sjo we performed MRI spectroscopy, which did not reveal the € gren-Larsson syndrome. Whole abnormal lipid peak as seen in Sjo exome sequencing was performed and pathogenic mutations were not detected in ALDH3A2 nor in any other gene related to HSP. However, mutations where detected in an other gene related to aldehyde metabolism. Conclusion: Spastic paraplegia and crystalline retinopathy might be a new recognisable phenotype of HSP. We are looking for additional subjects to validate candidate genes.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1050 P2-135 Clinical cases about uncommon genotype of congenital disorders of glycosylation ~ oz, R. Calvo Medina, A. Calvo-Cillan, M. Sanchez Mun M. mantecon Barranco, M.A. Aviles-tirado, E. Moreno Medinilla, J. Martinez Anton. Department of Paediatric Neurology, HRU, Malaga, Spain Introduction: Congenital disorder of glycosylation (CDG) are a genetical diseases group due to defects in synthesis of glicans. It has been described 110 types.The most common genetics (more than 70%) being PMM2-CDG (CDG-Ia).There are few references in the literature to other genotypes. We present two clinical cases of non-PMM2-CDG patients that we currently follow. Case 1: Girl with controlled pregnancy, caesarean delivery. At birth presents hypotonia and hyperreflexia, dysmorphia with dysplastic ears, microcephaly, retromicrognathia, short neck, short upper limbs and small hands, hip dislocation. She was admitted in our hospital at 4 months of age due to the onset of partial seizures that progressed to seizure status and refractory epilepsy. Severe corticalsubcortical atrophy on CT scans and delayed myelination in MRI. EEG revealed a slow waves and occipital spikes. The extended study includes deficient carbohydrate transferrin (CDT) analysis that is altered, appearing in the genetics a mutation of the enzyme RFT1 (RFT1-CDG). She passed away at 18 month of age Case 2: Male with history of controlled pregnancy and caesarean delivery due to maternal interest (psychiatric illness). Newborn preterm of 35 weeks, small for gestational age. He had a developmental delay, since the first milestones along with dysmorphia (microcephaly, hypotelorism, micrognathia) and alternating strabismus. The CT cranial at 2 years shows a cortico-subcortical atrophy. In the extended study, CDT is included at 5 years, which was altered and in genetic study mutation of SSR4 linked to X (SSR4-CDG) was found. At present, the patient has an autism spectrum disorder
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and behavioural disorder. CONCLUSIONS Patients with multisystemic involvement, especially if it is accompanied by mild dysmorphism, neurological symptoms and/or psychomotor retardation, are candidates for the study of protein glycosylation disorders. Early study may allow genetic counselling, intervention to complications, and avoid multiple consultations with families.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1051 P2-136 Severe infantile acute encephalopathy and COG4 mutation: CDG IIJ n, Alfons Macaya Ruiz, Mireia del Toro Riera, Ana Felipe Rucia s. Pediatric Neurology, Hospital Universitari Vall d'Hebron, M. Giro University Aut onoma de Barcelona, Spain Objective and Methods: Type II congenital disorders of glycosylation (CDG) are a group of inherited multisystem disorders caused by defects in the processing of the protein-bound glycans either late in the endoplasmic reticulum (ER) or in the Golgi compartment. Mutations in members of the Conserved Oligomeric Golgi (COG) complex cause CDG type II and are being increasingly diagnosed with widespread use of NGS. Mutations in the COG4 gene define the very unusual CDG-IIj subtype. We report the second patient with COG4eassociated encephalopathy. Results: A 3 year-old male, the son of consanguineous Moroccan parents, had normal development until age 6 mo when, after febrile illness, presented with acute encephalopathy. Motor regression and developmental delay were noted thereafter. Evaluation at 3 years showed mild dysmorphic features, no visceromegalies, profound retardation, progressive microcephaly and hypotonic tetraparesis. Hyperlactacidemia, hyperammonemia and mild/diffuse white and grey matter loss on brain MRI were noted. A subsequent dental infection at 3 years was complicated by obtundation, dehydration, increased serum transaminases, pancytopenia, coagulopathy and hyperammonemia. Metabolic screening was normal/nonspecific and ophthalmological/cardiological investigations were also normal. Study of sialotransferrin isoforms showed a CDG type II profile. WES identified a homozygous c.973T>A variant in COG4, leading to a p.F325I substitution. Functional studies using the brefeldin A assay in patient's skin fibroblasts revealed an alteration in retrograde Golgi-to-ER transport. Conclusion: This is the second case described in the literature linking COG4 mutations with CDG II, a further metabolic defect presenting as infantile acute neurological deterioration with multiorgan failure.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1052 P2-137 Early onset respiratory failure in an infant with mitochondrial myopathy A. Fadilah, P.S. Baxter. Department of Paediatric Neurology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, United Kingdom Objective: Classical neurological causes of early infantile respiratory failure and weakness include congenital myopathies, myotonic dystrophy, anterior horn cell disorders, and cervical myelopathy. Here we describe an infant with an additional cause, mitochondrial myopathy, in a report which also illustrates the value of imaging pre-biopsy. Methods: Case report. Results: An 8 week old girl, the second child of healthy unrelated parents, presented after an intercurrent illness with hypotonia, weakness and feeding difficulty. There had been reduced movements during pregnancy and she was said to have “never really moved properly” in early infancy.
By 12 weeks she required nasogastric feeds and by age 4 months developed respiratory failure requiring ventilator support. On examination she was visually and socially interactive with normal cranial nerve findings, axial and limb hypotonia, weak antigravity movements, proximal muscle wasting but no contractures. Reflexes were normal. Plasma CK, lactate, carnitine, ubiquinone, urine organic acids, ECG, echocardiogram, nerve conduction studies and EMG of vastus medialis were normal. EMG showed myopathic potentials in tibialis anterior and biceps. Quadriceps muscle biopsy showed type 2 predominance and fatty replacement. MRI of the brain and spine was normal. MRI of thighs and calves revealed signal change in posterior compartment and extensor digitorum longus muscles but no atrophy. Muscle biopsy from the latter showed variation in fibre size, increased adipose and connective tissue, type 2 fibre predominance and lipid myopathy, associated with generally reduced respiratory chain enzyme activity on biochemical analysis. Later genetic analysis showed compound heterozygosity for 2 mutations in the RRM2B gene, consistent with mitochondrial DNA depletion syndrome. Her condition progressed and she died aged 14 months. Conclusion: Our case indicates that mitochondrial myopathies should be included in the differential diagnosis of early onset respiratory failure and weakness. It also emphasises the importance of imaging in selecting muscles for diagnostic biopsy.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1053 P2-138 Congenital metabolism diseases of neurotransmitters in pediatric neurology: Clinical description and neurological tracing of a group of patients M. Troncoso, D. Munoz, P. Santander, I. Ruiz, C. Rojas, M.J. Hidalgo, V. Naranjo, L. Troncoso, A. Barrios. Department of n Hospital, Pediatric Neurology and Psychiatry, San Borja Arriara University of Chile, Santiago, Chile Introduction: The neurological manifestations of congenital metabolism diseases of aminergic neurotransmitters (NT) are diverse. The autosomal dominant Dopa-responsive dystonia (DRD), with deficiency of GTP cyclohydrolase1 (GTPCH1), is the most common type, with a satisfactory response to treatment. Objective: To describe clinical features, response to treatment and outcome of patients diagnosed with inborn errors of aminergic neurotransmitters in our center. Methods: A retrospective descriptive study and a prospective follow-up of 17 patients. Review of clinical records Results: 17 patients. 16/17 exhibit DRD. 12/16 women. On 9/16 the average was 5 years age at onset and 9.5 years at diagnosis. In all patients the initial symptom was gait disturbance with diurnal fluctuation, lower limb (8/9) and upper limb (8/9) dystonia, trunk dystonia (3/9), tremor (3/9). Adult relatives (7/16) begin symptoms between 20 and 40 years: focal dystonia, parkinsonism. The mode of inheritance was autosomal dominant. The phenylalanine test was guiding. Diagnosis is confirmed with measurement of CSF levels of NT: low concentrations of neopterins, biopterins and 5HIAA HVA suggest deficiency of GTPCH1. Positive genetic study in 2 families. The response to levodopa treatment was satisfactory. One patient (1/17) shows a deficit of L-Dopa decarboxylase with severe global psychomotor retardation, fever, hypotonia, epilepsy, dystonia, and fatal outcome. Conclusion: In our series predominates DRD, with clinical features and response to treatment classically described. Early diagnosis allows prompt treatment with improvement of symptoms and favorable course.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1054
processing started by correcting for eddy current distortions and head motion using FMRIB's Diffusion Toolbox. FA, RD and MD maps for each patient and control were calculated using the eigenvalues extracted from the diffusion tensors. Results: PKU patients showed decreased MD values as compared with controls in the body and splenium of the corpus callosum, superior longitudinal fasciculus and in the corona radiata. RD values followed a very similar pattern, although decreased RD values were also found in the posterior limb of the internal capsule. FA values showed no significant differences between groups. Decreased MD values within the body of the corpus callosum significantly correlated negatively with age (r ¼ 0.77, p < 0.001) and concurrent phenylalanine values (r ¼ 0.76, p < 0.001). RD values in the body of the corpus callosum also significantly and negatively correlated with age (r ¼ 0.73, p < 0.002). Conclusions: WM abnormalities were present even in early treated PKU. Decreased MD values correlated significantly with concurrent Phe levels.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1048 P2-133 Hunter and fragile-X syndromes in a family with Xq27.3-q28 deletion that involves FMR1 and IDS genes S. Aguilera-Albesa, A. Mosquera-Gorostidi, I. Naberan-Mardaras, N. Gorria-Redondo, I. Urriza-Ripa, M.E. Yoldi-Petri, M.A. Ramos-Arroyo, M.J. Coll, E. Aznal, F. Sanchez-Valverde. Complejo Hospitalario de Navarra, Navarrabiomed, Pamplona, Spain Objective: To describe the different clinical presentation and outcome of a brother and a sister, carrying the same deletion involving FMR1 and IDS genes. Methods: Family case description. Results: The brother presented at 6-mo with psychomotor delay, macrosomia, mild umbilical hernia and no dysmorphic features. At 10-month-old he suffered a hemi- convulsive status. Then cerebral MRI revealed leukoencephalopathy with corpus callosum cysts. Additional investigations showed mild hepatomegaly, increased excretion of heparan and dermatan sulphate bands, and a nearly undetectable activity of iduronate-2-sulfatase enzyme in leukocytes. Molecular studies revealed a Xq27.3- q28 deletion involving FMR1 and IDS genes. He started enzymatic replacement therapy with idursulfase from 12-mo. At 3-yo, anthropometric values were >P97 but decreased afterwards. Coarse facial features appeared progressively together with a carpal tunnel syndrome that required surgery at 3-yo. At 6-yo he presents severe global psychomotor delay with no expressive language, walking with support, joints deformations and repetitive motor and self-injury behaviours. Urine excretion of glycosaminoglycans remains reduced by 50%. The sister carried the same deletion, confirmed prenatally. She presented with postnatal macrosomia, sparse hair growth in fronto-temporal regions and developmental delay. She walks independently from 24mo but expressive language is not present at 3-yo, with extreme shyness. Her cerebral MRI and urine excretion of glycosaminoglycans are normal. The mother carried the same deletion but she is asymptomatic. Enzymatic and skewed patterns studies in the sister and mother are on course. Conclusion: The coexistence of Hunter and Fragile-X syndromes is rare. In a boy with a deletion affecting both IDS and FMR1 genes, the diagnosis of mucopolysaccharidosis may be delayed by a more prominent neurological presentation in the absence of systemic features during the first year of life. In this case, the neuroimaging provided an earlier diagnosis.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1049
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P2-134 Spastic paraplegia with crystalline retinopathy: A recognisable phenotype? Patrick Verloo, Patricia Delbeke, Rudy Van Coster. Department of Paediatrics, Division of Paediatric Neurology, Ghent University Hospital, Ghent, Belgium Objective: Genetic diagnosis of hereditary spastic paraparesis (HSP) is often challenging because of lack of typical clinical or biochemical abnormalities. Case: An eight year old girl presented at the consultation with severe spastic paraparesis which had developed slowly over the last two years. More recently, a tremor in the hand became apparent. Perinatal history was unremarkable and early milestones were reached within normal limits. Cognitive functioning was normal. Dysmorphic features and skin lesions were not seen. Cerebral MRI and MRI of the spine were normal. Work-up was done for hereditary spastic paraparesis. Results: Fundoscopy showed a crystalline retinopathy as is typically seen in € gren-Larsson syndrome. As ichtyosis was absent in this patient Sjo we performed MRI spectroscopy, which did not reveal the € gren-Larsson syndrome. Whole abnormal lipid peak as seen in Sjo exome sequencing was performed and pathogenic mutations were not detected in ALDH3A2 nor in any other gene related to HSP. However, mutations where detected in an other gene related to aldehyde metabolism. Conclusion: Spastic paraplegia and crystalline retinopathy might be a new recognisable phenotype of HSP. We are looking for additional subjects to validate candidate genes.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1050 P2-135 Clinical cases about uncommon genotype of congenital disorders of glycosylation ~ oz, R. Calvo Medina, A. Calvo-Cillan, M. Sanchez Mun M. mantecon Barranco, M.A. Aviles-tirado, E. Moreno Medinilla, J. Martinez Anton. Department of Paediatric Neurology, HRU, Malaga, Spain Introduction: Congenital disorder of glycosylation (CDG) are a genetical diseases group due to defects in synthesis of glicans. It has been described 110 types.The most common genetics (more than 70%) being PMM2-CDG (CDG-Ia).There are few references in the literature to other genotypes. We present two clinical cases of non-PMM2-CDG patients that we currently follow. Case 1: Girl with controlled pregnancy, caesarean delivery. At birth presents hypotonia and hyperreflexia, dysmorphia with dysplastic ears, microcephaly, retromicrognathia, short neck, short upper limbs and small hands, hip dislocation. She was admitted in our hospital at 4 months of age due to the onset of partial seizures that progressed to seizure status and refractory epilepsy. Severe corticalsubcortical atrophy on CT scans and delayed myelination in MRI. EEG revealed a slow waves and occipital spikes. The extended study includes deficient carbohydrate transferrin (CDT) analysis that is altered, appearing in the genetics a mutation of the enzyme RFT1 (RFT1-CDG). She passed away at 18 month of age Case 2: Male with history of controlled pregnancy and caesarean delivery due to maternal interest (psychiatric illness). Newborn preterm of 35 weeks, small for gestational age. He had a developmental delay, since the first milestones along with dysmorphia (microcephaly, hypotelorism, micrognathia) and alternating strabismus. The CT cranial at 2 years shows a cortico-subcortical atrophy. In the extended study, CDT is included at 5 years, which was altered and in genetic study mutation of SSR4 linked to X (SSR4-CDG) was found. At present, the patient has an autism spectrum disorder
e140
e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 2 1 ( 2 0 1 7 ) e 1 2 3 ee 1 4 0
and behavioural disorder. CONCLUSIONS Patients with multisystemic involvement, especially if it is accompanied by mild dysmorphism, neurological symptoms and/or psychomotor retardation, are candidates for the study of protein glycosylation disorders. Early study may allow genetic counselling, intervention to complications, and avoid multiple consultations with families.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1051 P2-136 Severe infantile acute encephalopathy and COG4 mutation: CDG IIJ n, Alfons Macaya Ruiz, Mireia del Toro Riera, Ana Felipe Rucia s. Pediatric Neurology, Hospital Universitari Vall d'Hebron, M. Giro University Aut onoma de Barcelona, Spain Objective and Methods: Type II congenital disorders of glycosylation (CDG) are a group of inherited multisystem disorders caused by defects in the processing of the protein-bound glycans either late in the endoplasmic reticulum (ER) or in the Golgi compartment. Mutations in members of the Conserved Oligomeric Golgi (COG) complex cause CDG type II and are being increasingly diagnosed with widespread use of NGS. Mutations in the COG4 gene define the very unusual CDG-IIj subtype. We report the second patient with COG4eassociated encephalopathy. Results: A 3 year-old male, the son of consanguineous Moroccan parents, had normal development until age 6 mo when, after febrile illness, presented with acute encephalopathy. Motor regression and developmental delay were noted thereafter. Evaluation at 3 years showed mild dysmorphic features, no visceromegalies, profound retardation, progressive microcephaly and hypotonic tetraparesis. Hyperlactacidemia, hyperammonemia and mild/diffuse white and grey matter loss on brain MRI were noted. A subsequent dental infection at 3 years was complicated by obtundation, dehydration, increased serum transaminases, pancytopenia, coagulopathy and hyperammonemia. Metabolic screening was normal/nonspecific and ophthalmological/cardiological investigations were also normal. Study of sialotransferrin isoforms showed a CDG type II profile. WES identified a homozygous c.973T>A variant in COG4, leading to a p.F325I substitution. Functional studies using the brefeldin A assay in patient's skin fibroblasts revealed an alteration in retrograde Golgi-to-ER transport. Conclusion: This is the second case described in the literature linking COG4 mutations with CDG II, a further metabolic defect presenting as infantile acute neurological deterioration with multiorgan failure.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1052 P2-137 Early onset respiratory failure in an infant with mitochondrial myopathy A. Fadilah, P.S. Baxter. Department of Paediatric Neurology, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, United Kingdom Objective: Classical neurological causes of early infantile respiratory failure and weakness include congenital myopathies, myotonic dystrophy, anterior horn cell disorders, and cervical myelopathy. Here we describe an infant with an additional cause, mitochondrial myopathy, in a report which also illustrates the value of imaging pre-biopsy. Methods: Case report. Results: An 8 week old girl, the second child of healthy unrelated parents, presented after an intercurrent illness with hypotonia, weakness and feeding difficulty. There had been reduced movements during pregnancy and she was said to have “never really moved properly” in early infancy.
By 12 weeks she required nasogastric feeds and by age 4 months developed respiratory failure requiring ventilator support. On examination she was visually and socially interactive with normal cranial nerve findings, axial and limb hypotonia, weak antigravity movements, proximal muscle wasting but no contractures. Reflexes were normal. Plasma CK, lactate, carnitine, ubiquinone, urine organic acids, ECG, echocardiogram, nerve conduction studies and EMG of vastus medialis were normal. EMG showed myopathic potentials in tibialis anterior and biceps. Quadriceps muscle biopsy showed type 2 predominance and fatty replacement. MRI of the brain and spine was normal. MRI of thighs and calves revealed signal change in posterior compartment and extensor digitorum longus muscles but no atrophy. Muscle biopsy from the latter showed variation in fibre size, increased adipose and connective tissue, type 2 fibre predominance and lipid myopathy, associated with generally reduced respiratory chain enzyme activity on biochemical analysis. Later genetic analysis showed compound heterozygosity for 2 mutations in the RRM2B gene, consistent with mitochondrial DNA depletion syndrome. Her condition progressed and she died aged 14 months. Conclusion: Our case indicates that mitochondrial myopathies should be included in the differential diagnosis of early onset respiratory failure and weakness. It also emphasises the importance of imaging in selecting muscles for diagnostic biopsy.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1053 P2-138 Congenital metabolism diseases of neurotransmitters in pediatric neurology: Clinical description and neurological tracing of a group of patients M. Troncoso, D. Munoz, P. Santander, I. Ruiz, C. Rojas, M.J. Hidalgo, V. Naranjo, L. Troncoso, A. Barrios. Department of n Hospital, Pediatric Neurology and Psychiatry, San Borja Arriara University of Chile, Santiago, Chile Introduction: The neurological manifestations of congenital metabolism diseases of aminergic neurotransmitters (NT) are diverse. The autosomal dominant Dopa-responsive dystonia (DRD), with deficiency of GTP cyclohydrolase1 (GTPCH1), is the most common type, with a satisfactory response to treatment. Objective: To describe clinical features, response to treatment and outcome of patients diagnosed with inborn errors of aminergic neurotransmitters in our center. Methods: A retrospective descriptive study and a prospective follow-up of 17 patients. Review of clinical records Results: 17 patients. 16/17 exhibit DRD. 12/16 women. On 9/16 the average was 5 years age at onset and 9.5 years at diagnosis. In all patients the initial symptom was gait disturbance with diurnal fluctuation, lower limb (8/9) and upper limb (8/9) dystonia, trunk dystonia (3/9), tremor (3/9). Adult relatives (7/16) begin symptoms between 20 and 40 years: focal dystonia, parkinsonism. The mode of inheritance was autosomal dominant. The phenylalanine test was guiding. Diagnosis is confirmed with measurement of CSF levels of NT: low concentrations of neopterins, biopterins and 5HIAA HVA suggest deficiency of GTPCH1. Positive genetic study in 2 families. The response to levodopa treatment was satisfactory. One patient (1/17) shows a deficit of L-Dopa decarboxylase with severe global psychomotor retardation, fever, hypotonia, epilepsy, dystonia, and fatal outcome. Conclusion: In our series predominates DRD, with clinical features and response to treatment classically described. Early diagnosis allows prompt treatment with improvement of symptoms and favorable course.
http://dx.doi.org/10.1016/j.ejpn.2017.04.1054