Glutaric Acidemia, A Preliminary Survey

ObjectiveGlutaric aciduria type 1 (GAL 1) is a cerebral organic academia, which manifests as encephalopathy with long-term neurological handicap. In this study, clinical presentation, neuroimaging, molecular finding of CGDH mutation of our patients were reviewed.Materials and MethodsThis was a descriptive and cross-sectional study. Patients in whom GLA1 were suspected by clinical manifestation, neuroimaging or metabolic study during last 10 years (2001-2011) in pediatric Mofid hospital were tested for CGDH gene mutation. ResultsPatients age range at study times were 15-102 months. Patients’ ages at diagnosis time were 5-17 months. All of parents of our patients were relative. Clinical presentation in order were: developmental delay (54%), macrocephaly and seizure (45%), dystonia (36%), neurodevelopmental regression (27%), acute encephalopathy after fever and vaccination (18%). Neuroimaging finding in brain CT scan and MRI in majority of patients included brain atrophy, widely open sylvian fissure and basal ganglia calcification. Enzymatic study was not performed. Molecular testing results of CGDH in all patients were abnormal. A new mutation in CGDH was detected in our patients.ConclusionGLA1 has a protean clinical presentation with different neurological sequel. It is essential to detect patients by newborn screening . Molecular testing and enzymatic study of CGDH activity establish the diagnosis of patients and prenatal diagnosis, too

Plasma Pyridoxal 5´-Phosphate Level in Children with Intractable and Controlled Epilepsy

How to Cite This Article: Pirzadeh Z, Ghofrani M, Mollamohammadi M. Plasma Pyridoxal 5´-Phosphate Level in Children with Intractable and Controlled Epilepsy. Iran J Child Neurol. Spring 2017; 11(2):31-36. AbstractObjectiveIntractable epilepsy is a serious neurologic problem with different etiologies. Decreased levels of pyridoxal phosphate in cerebral spinal fluid of patients with intractable epilepsy due to pyridoxine dependency epilepsy are reported. The aim of this study was to compare plasma pyridoxal 5´-phosphate level in patients with intractable and controlled epilepsy.Materials & Methods This cross- sectional analytic study included 66 epileptic children, 33 patients with controlled and 33 patients with intractable epilepsy, after neonatal period up to 15 yr old of age. Thirty-three patients with intractable epilepsy (10- 162 months) and 33 patients with controlled epilepsy (14-173 months) were enrolled. The study was conducted in Pediatric Neurology Clinic of Mofid Children Hospital, Tehran, Iran from January 2010 to December 2010. Patients’ clinical manifestations, laboratory and neuroimaging findings were collected. Non-fasting plasma 5´- pyridoxal phosphate levels of these subjects were assessed by high-pressure liquid chromatography.Results Mean plasma 5´- pyridoxal phosphate level (PLP) in patients with controlled epilepsy was 76.78±37.24 (nmol/l) (15.5-232.4). In patients with intractable epilepsy, mean plasma 5´- pyridoxal phosphate was 98.67± 80.58 (25.5- 393) nmol/l. There was no statistically significant difference between plasma pyridoxal phosphate levels of these two groups (P═0.430).Conclusion Pyridoxine dependent epilepsy is under diagnosed because it is manifested by various types of seizures. Plasma pyridoxal phosphate levels did not differ in our patients with intractable or controlled epilepsy. If PDE is suspected on clinical basis, molecular investigation of ALDH7A1 mutations, as feasible test, until PDE biomarkers becomes available is recommended. References1.Cown LD. The epidemiology of the epilepsies in children. Ment Retard Dev Disabil Res Rev 2002;8(3):171-81.2.French JA. Refractory epilepsy: clinical overview. Epilepsia 2007;48 Suppl 1:3-7.3.Oliveira R, Pereira C, Rodrigues F, Alfaite C, Garcia P, Robalo C, et al. Pyridoxine-dependent epilepsy due to antiquitin deficiency: achieving a favourable outcome. Epileptic Disord 2013;15(4):400-6.4.Baxter P. Pyridoxine-dependent and pyridoxine-responsive seizures. Dev Med Child Neurol 2001; 43(6):416-20.5.Akhoondian J, Talebi S. High dose oral pyridoxine for treatment of pediatric recurrent intractable seizure. MJIRI 2004; 17(4):301-4.6.Ramachandrannair R, Parameswaran M. Prevalence of pyridoxine dependent seizures in south Indian children with early onset intractable epilepsy: A hospital based prospective study. Eur J Paediatr Neurol 2005;9(6):409- 13.7. Baxter P. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in UK. Arch Dis Child 1999;81(5):431-3.8. Yaghini O, Shahkarami MA, Shamsaii S. Neglected atypical pyridoxine dependent seizures. Iran J Pediatr 2010;20(4):498-501.9. Lumeng L, Lui A, Li TK. Plasma content of B6 vitamers and its relationship to hepatic rat B6 metabolism. J Clin Inves 1980;66(4):686-95.10. Clayton PT. B6-responsive disorders: a model of vitamin dependency. J Inherit Metab Dis 2006;29(2-3):317-26.11. Goyal M, Fequiere PR, McGrath TM, Hyland K. Seizures with decreased levels of pyridoxal phosphate in cerebrospinal fluid. Pediatr Neurol 2013;48(3):227-31.12. Footitt EJ, Heales SJ, Mills PB, Allen GF, Oppenheim M, Clayton PT. Pyridoxal 5’-phosphate in cerebrospinal fluid; factors affecting concentration. J Inherit Metab Dis 2011; 34(2):529-38.13. Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5’-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004.Am J Clin Nutr 2008;87(5):1446-54.14. Setiawan B, Giraud DW, Driskell JA. Vitamin B-6 inadequacy is prevalent in rural and urban Indonesian children. J Nutr 2000;130(3):553-8.15. Shin YS, Rasshofer R, Endres W. Pyridoxal-5’-phosphate concentration as marker for vitamin-B6-dependent seizures in the newborn. Lancet 1984;2(8407):870-1.16. Pérez B, Gutiérrez-Solana LG, Verdú A, Merinero B, Yuste-Checa P, Ruiz-Sala P, et al. Clinical, biochemical, and molecular studies in pyridoxine-dependent epilepsy. Antisense therapy as possible new therapeutic option. Epilepsia 2013;54(2):239-48.17. Gospe SM. Pyridoxine-dependent seizures: findings from recent studies pose new questions. Pediatr Neurol 2002;26(3):181-5.18. Plecko B, Hikel C, Korenke GC, Schmitt B, Baumgartner M, Baumeister F, et al. Pipecolic acid as a diagnostic marker of pyridoxine-dependent epilepsy. Neuropediatrics 2005;36(3):200-5.19. Albersen M, Groenendaal F, van der Ham M, de Koning TJ, Bosma M, Visser WF, et al. Vitamin B6 vitamer concentrations in cerebrospinal fluid differ between preterm and term newborn infants. Pediatrics 2012;130(1):e191-8.20. Ormazabal A, Oppenheim M, Serrano M, García-Cazorla A, Campistol J, Ribes A, et al. Pyridoxal 5’-phosphate values in cerebrospinal fluid: reference values and diagnosis of PNPO deficiency in paediatric patients. Mol Genet Metab 2008;94(2):173-7.21. Stockler S, Plecko B, Gospe SM Jr, Coulter-Mackie M, Connolly M, van Karnebeek C, Mercimek-Mahmutoglu S, Hartmann H, Scharer G, Struijs E, Tein I, Jakobs C, Clayton P, Van Hove JL. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up.Mol Genet Metab. 2011 Sep- Oct;104(1-2):48-60. doi: 10.1016/j.ymgme.2011.05.014. Epub 2011 May 24.22. Steinberg SJ, Dodt G, Raymond GV, Braverman NE, Moser AB, Moser HW. Peroxisome biogenesis disorders. Biochim Biophys Acta 2006;1763(12):1733-48.23. Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, et al. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med 2006;12(3):307-9.24. Struys EA, Nota B, Bakkali A, Al Shahwan S, Salomons GS, Tabarki B. Pyridoxine-dependent epilepsy with elevated urinary α-amino adipic semialdehyde in molybdenum cofactor deficiency. Pediatrics 2012; 130(6):e1716-9.25. Struys EA, Bok LA, Emal D, Houterman S, Willemsen MA, Jakobs C. The measurement of urinary Δ¹- piperideine-6-carboxylate, the alter ego of α-aminoadipic semialdehyde, in Antiquitin deficiency. J Inherit Metab Dis 2012;35(5):909-16.26. Nam SH, Kwon MJ, Lee J, Lee CG, Yu HJ, Ki CS, et al. Clinical and genetic analysis of three Korean children with pyridoxine-dependent epilepsy. Ann Clin Lab Sci 2012;42(1):65-72.27. Yang Z, Yang X, Wu Y, Wang J, Zhang Y, Xiong H, et al. Clinical diagnosis, treatment, and ALDH7A1 mutations in pyridoxine-dependent epilepsy in three Chinese infants. PLoS One 2014;9(3):e92803.28. Jung S, Tran NT, Gospe SM Jr, Hahn SH. Preliminary investigation of the use of newborn dried blood spots for screening pyridoxine-dependent epilepsy by LC-MS/MS. Mol Genet Metab 2013;110(3):237-40.

Plasma Pyridoxal 5´-Phosphate Level in Children with Intractable and Controlled Epilepsy

Objective Intractable epilepsy is a serious neurologic problem with different etiologies. Decreased levels of pyridoxal phosphate in cerebral spinal fluid of patients with intractable epilepsy due to pyridoxine dependency epilepsy are reported. The aim of this study was to compare plasma pyridoxal 5´-phosphate level in patients with intractable and controlled epilepsy. Materials & Methods This cross- sectional analytic study included 66 epileptic children, 33 patients with controlled and 33 patients with intractable epilepsy, after neonatal period up to 15 yr old of age. Thirty-three patients with intractable epilepsy (10- 162 months) and 33 patients with controlled epilepsy (14-173 months) were enrolled. The study was conducted in Pediatric Neurology Clinic of Mofid Children Hospital, Tehran, Iran from January 2010 to December 2010. Patients’ clinical manifestations, laboratory and neuroimaging findings were collected. Non-fasting plasma 5´- pyridoxal phosphate levels of these subjects were assessed by high-pressure liquid chromatography. Results Mean plasma 5´- pyridoxal phosphate level (PLP) in patients with controlled epilepsy was 76.78±37.24 (nmol/l) (15.5-232.4). In patients with intractable epilepsy, mean plasma 5´- pyridoxal phosphate was 98.67± 80.58 (25.5- 393) nmol/l. There was no statistically significant difference between plasma pyridoxal phosphate levels of these two groups (P═0.430). Conclusion Pyridoxine dependent epilepsy is under diagnosed because it is manifested by various types of seizures. Plasma pyridoxal phosphate levels did not differ in our patients with intractable or controlled epilepsy. If PDE is suspected on clinical basis, molecular investigation of ALDH7A1 mutations, as feasible test, until PDE biomarkers becomes available is recommended. Keywords: Pyridoxine Dependent Epilepsy; Intractable Epilepsy; Plasma Pyridoxal Phosphate Level; Childre

Pregabalin in childhood epilepsy: a clinical trial study

How to Cite This Article: Mollamohammadi M, Tonekaboni SH, Pirzadeh Z, Vahedian M . Pregabalin in Childhood Epilepsy: A Clinical TrialIran J Child Neurol. 2014 Autumn;8(4): 62-65.AbstractObjectiveThe prevalence of active epilepsy is about 0.5–1%, and approximately 70% of patients are cured with first anti-epileptic drugs and the remaining patients need multiple drugs. Pregabalin as an add-on therapy has a postive effect on refractory seizures in adults. To the best of our knowledge, there is no research with this drug in childhood epilepsy. We use pregabalin in children with refractory seizures as an add-on therapy. The objective of this study is to evaluate the effects of pregabalin in the reduction of seizures for refractory epilepsy.Material & MethodsForty patients with refractory seizures who were referred to Mofid Children’s Hospital and Hazrat Masoumeh Hospital were selected. A questionnaire based on patient record forms, demographic data (age, gender,…), type of seizure, clinical signs, EEG record, imaging report, drugs that had been used, drugs currently being used, and the number of seizures before and after Pregabalin treatment was completed. We checked the number of seizures after one and four months.ResultsAfter one month, 26.8% of patients had more than a 50% reduction in seizures and 14.6% of these patients were seizure-free; 12.2% had a 25–50% reduction; and approximately 61% had less than a 25% reduction or no change in seizures.After the fourth month, 34.1% of patients had more than a 50% reduction in seizures and 24.4% of these patients were seizure-free. Additionally, 65.9% of patients had less than 50% reduction in seizures (9.8% between 25–50% and 56.1% less than 25% or without improvement).ConclusionWe recommend Pregabalin as an add-on therapy for refractory seizures (except for myoclonic seizures) for children.ReferencesKwan P., Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000;342(5):314-9.Mikati MA. Seizures in childhood. In: Kliegmann RM, Behrman RE, Jenson HB, Stanton BF, editors. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, Pa:Saunders Elsevier. 2011.P.2013-2039.Camfield PR, Camfield CS. Pediatric Epilepsy. In: Swaiman KF, editors. Swaiman`s pediatric neurology: Principles and Practice.7th ed. Edinburgh: Elsevier Saunders; 2012.P 703-710.Piña-Garza EJ. Fenichel’s clinical pediatric neurology. Altered States of Consciousness. 7th ed. Elsevier Saunder. 2013.P.47-75.Austin JK, Smith S, Risinger MW, McNehs AM. Childhood epilepsy and asthma comparison of quality of life. Epilepsia 1994:35(3):608-15.Farvwell JR, Dodrill CB, Batzel LW. Neuropsychological abilities of children with epilepsy. Epilepsia 1985;26(5):395-400.Kotagal P, Rothner AD, Erenberg G, Cruse RP, Wyllie E. Complex partial seizures of childhood onset. Arch Neurol 1987:44(11):1177-80.Miller R, Frame B, Corrigan B, Burger P, Backbrader H, Garofalo EA, et al. Exposure- response analysis of pregabalin add- on treatment of patients with refractory partial seizures. Clin Pharmacol Ther 2003;73(6):491-505.Fink K, Dooley DJ, Meder WP, Suman-Chauhan N, Duffy S, Clusmann H, et al. Inhibition of neuronal ca(2+) influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology 2002;42(2):229-36.Topol A. Pregabalin for epilepsy. New medicines profile 2004 November; (04/12):1-3.Arroyo S, Anhut H, Kugler AR, Lee CM, Knapp LE, Garofalo EA, et al. Pregabalin add-on treatment: a randomized, double-blind, placebo-controlled, doseresponse study in adults with partial seizures. Epilepsia 2004; 45(1):2-7.Beydoun A, Uthman BM, Kugler AR, Greiner MJ, Knapp LE, Garoflo EA. Safely and efficacy of two pregabalin regimens for add-on treatment of partial epilepsy. Neurology 2005;64(3):475-80.French JA, Kugler AR, Robbins JL, Knapp LE, Garoflo EA. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology 2003;60(10):1631-7.Carreno M, Maestro I, Molins A, Donaire A, Falip M, Becerra JL, et al. Pregabalin as add-on therapy for refractory seizures in every day clinical practice. Seizure 2007;16(8):709-12.Jan MM, Zuberi SA, Alsaihati BA. Pregabalin: Preliminary experience in intractable childhood epilepsy. Pediatr Neurol 2008;40(5):347-50.Chisanga E, Manford M. Pregabalin drug information. NHS foundation trust. March 2013.Gil-Nagel A. Zaccara G. Baldinetti F. Leon T. Add-on treatment with pregabalin for partial seizures with or without generalization: pooled data analysis of four randomized placebo-controlled trials. Seizure 2009;18(3):184-92

Molecular Investigation of Glutaric Aciduria Type1 in Iran

Glutaric Acidemia, Type I (GA I), was first described in 1975. The disease is caused by a genetic deficiency of the enzyme, Glutaryl-CoA Dehydrogenase (GCD), which leads to the buildup of Glutaric acid in the tissues and its excretion in the urine of affected patients. GCD is involved in the catabolism of the amino acids, Lysine, Hydroxylysine, and Tryptophan. Over 200 cases of GA I have been reported in the medical literature. GA I is one of the most common organic acidemias and has an estimated incidence of about 1 in 50,000 live births.Because of the initial slow progression of clinical symptoms, GA I is frequently undiagnosed until an acute metabolic crisis occurs. A total of 25 unrelated patients suspected to GA1 were investigated in our study. Genomic DNA was extracted from peripheral blood cells of the 25 probands whom were biochemically and/or clinically and/or neuro-radiologically suspected to GA1. 15 of them had elevated glutaric acid in the urine organic acid test.PCR and direct sequencing of all 11 exons and their flanking region of the GCDH gene were examined.Some of them were investigated for known mutation in the other their family members. Fifteen patients had homozygous mutations and 10 patients were normal for GCDH gene. Our Results Showed:• 60% Known mutation were found in our 15 patients• 80% can be detected by 4 exons sequencing so for molecular investigatins exon 6, 7, 8, 10 are good choice for beginning of analysis• 33% was mutation in exon 7, so because of the cost of genetic diagnosis we suggest that investigation begin with this exon.• Pro 348 Leu was most detected 20%.• 40% are new mutations wich will be investigated for phenotype Genotype Correlations

Clinicopathological Study of 307 Patients with Lichen Planus Actinicus and Pigmentosus Referred to Razi Skin Hospital from 2016 to 2021

Introduction: The two less-known subtypes of lichen planus (LP) are lichen planus actinicus (LPA) and lichen planus pigmentosus (LPP), with the highest prevalence in the Middle East. Objectives: We aimed to evaluate the clinicopathological profile of these patients. Methods: 307 cases including 184 LPA and 123 LPP patients were recruited from the registered pathology reports of Razi Skin Hospital of Tehran from April 2016 to March 2021. The clinical features and pathological reports were extracted and analyzed. Results: Among 307 patients, 117 (63.9%) in the LPA group and 88 (71.5%) in the LPP group were women. Duration of disease ranged from 1 month to 20 years and 1 month to 12 years in the LPA and LPP groups, respectively. Face (159 patients), limbs (68), and neck (23) were the most frequent sites of involvement in LPA patients, whereas face (60 patients), limbs (47), and trunk (42) were more commonly involved in the LPP patients. Pruritus and oral mucosal lesions were found with similar frequency in both groups. Pathological evaluation showed vacuolar degeneration of basal layer (100%), lymphocytes infiltration (97.3%), and melanin incontinence (58.2%) as the most frequent findings in LPA and vacuolar degeneration of basal layer (100%), lymphocytes infiltration (100%), and melanin incontinence (52/8%) as the most frequent findings in LPP cases.Conclusion: LPA and LPP were both more prevalent among women.  Face was the most common site of involvement in both LPA and LPP. Vacuolar degeneration, lymphocyte infiltration, melanin incontinence, and hyperkeratosis were more common histological findings in this study

A Case Report of Schimke Immuno-Osseous Dysplasia: A Rare Autosomal Recessive Disorder

Schimke immune-osseous dysplasia (SIOD) is a rare autosomal recessive disorder presented with specific facial features, skeletal dysplasia, steroid resistance nephrotic syndrome (SRNS) and cellular immune insufficiency. This is a SIOD case reported from Iran. He was 5 years old boy when evaluated for proteinuria and short stature. In appearance, we detected hyperpigmented macules, kyphoscoliosis, and warty lesions. He developed progressive renal failure and steroid resistant nephrotic syndrome, so kidney biopsy was performed and revealed focal and segmental glomerulosclerosis. He didn’t respond to prednisolone and Calcineurin inhibitors. He had recurrent lymphopenia with low CD4/CD8 ratio. However lymphopenia respond to granulocyte colony-stimulating factor (G-CSF), he died with pneumonia and sepsis. Nephrotic syndrome due to focal segmental glomerulosclerosis may be accompanied by syndromes. In Qazvin province, we see autosomal recessive disorders more, because of consanguineous marriages. To the best of our knowledge, this is the fourth case of SIOD to be reported from Iran

Acute Poisoning in Children Referred to Qazvin Children Hospital(2009 to 2012)

Background: Acute poisoning in children (APC) is a preventable cause of pediatric emergency visits. Patterns of acute poisoning in children are different in various regions and times. Objectives: Theaimof this study was to assess the epidemiology of acute poisoning in children,whowere referred to the emergency department of Qods teaching hospital in Qazvin, Iran. Methods: In this descriptive, cross-sectional study, all children younger than 13 years old, admitted to the Qods teaching hospital in Qazvin (Iran), were assessed during September 2009 to September 2012. Demographic and clinical symptoms and signs of poisoned cases, poisonous agents and outcome of patients were studied. Results: Four hundreds and thirty-four (2.59% of total hospital admission) patients with APC were admitted to the emergency department during the study period; 63.36% were male. Overall, 345 (79.5%) cases were under 6 years old. Drugs (265 cases) were common agents for APC. The ingestion route was responsible in 391 of APC. Methadone, benzodiazepines and kerosene were the most frequent poisonous agents. Neurologic symptoms and signs (256 cases) were the most common presentation of APC. Fortyfive patients (10.36%) were admitted to the PICU. Three deaths (%0.06) occurred with monoxide carbon and methadone poisoning. Monoxide carbon poisoning was the deadliest agent. Conclusions: Acute poisoning in children is a serious preventable cause of hospital admissions. It is one of the differential diagnoses in patients with sudden onset of neurological, alimentary, respiratory symptoms and signs, who are visited at the emergency department. Parental awareness and education about keeping potential poisoning agents safely is essential to reduce APC in children