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Eyelid Myoclonia With Absence Seizures in a Child With l -2 Hydroxyglutaric Aciduria: Findings of Magnetic Resonance Imaging
Pediatric Neurology 46 (2012) 195e197
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Case Report
Eyelid Myoclonia With Absence Seizures in a Child With L-2 Hydroxyglutaric Aciduria: Findings of Magnetic Resonance Imaging Ahmet Mete MD a, *, Sedat Isikay MD b, Akif Sirikci MD a, Ayhan Ozkur MD a, Metin Bayram MD a a b
Department of Radiology, School of Medicine, Gaziantep University, Gaziantep, Turkey Department of Pediatric Neurology, School of Medicine, Gaziantep University, Gaziantep, Turkey
article information
abstract
Article history: Received 18 September 2011 Accepted 17 January 2012
L-2 hydroxyglutaric aciduria is a rare, autosomal recessively inherited metabolic disorder of organic acid metabolism. A 5-year-old boy presented with eyelid myoclonia with absences that proved difficult to control with first-line anticonvulsants. An electroencephalogram produced profoundly abnormal results, with generalized spike-and-wave discharges. The patient became seizure-free with a combination therapy of clonazepam, levetiracetam, and lamotrigine. Magnetic resonance imaging demonstrated subcortical white matter and basal ganglia alterations. Urinary organic acid analysis demonstrated increased excretion of L-2 hydroxyglutaric acid. Although rare, seizures can occur as a presenting sign of slowly progressing organic acidurias, e.g., L-2 hydroxyglutaric aciduria. Both eyelid myoclonia with absences and L-2 hydroxyglutaric aciduria comprise rare disorders. To our knowledge, this case report is the first of L-2 hydroxyglutaric aciduria presenting with symptomatic eyelid myoclonia with absences. Ó 2012 Elsevier Inc. All rights reserved.
Introduction L-2 hydroxyglutaric aciduria is a rare metabolic disorder characterized by a progressive neurologic syndrome of cerebellar and pyramidal signs, mental deterioration, tremor, and extrapyramidal signs during the first years of age. Seizures, epilepsy, and macrocephaly may constitute additional findings [1]. Metabolic disorders rarely present with seizures in isolation [2]. Seizures occur in more than 50% of patients with L-2 hydroxyglutaric aciduria, usually late in the course of the disease [3-5]. Eyelid myoclonia with absences constitutes a generalized epileptic condition clinically characterized by eyelid myoclonia with or without absence seizures, eye closure-induced electroencephalographic paroxysms, and photosensitivity. We present a 5-year-old boy who presented with eyelid myoclonia with absence seizures. He was subsequently diagnosed with L-2 hydroxyglutaric aciduria.
Case Report A 5-year-old boy was referred to us with a history of seizures during the previous 6 months, beginning with myoclonia of the eyelids. Within 2 months, the seizures worsened, and occurred many times a day. He was born at term after an uneventful pregnancy to nonconsanguineous healthy parents. Delivery was * Communications should be addressed to: Dr. Mete; Department of Radiology; School of Medicine; Gaziantep University; Sahinbey, 27310 Gaziantep, Turkey. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2012.01.008
normal. His birth weight was 3500 g (25th-50th centile), his height was 53 cm (25th-50th centile), and his head circumference was 34.5 cm (25th-50th centile). He was his parents’ first child. They described developmental delay in his motor, social, and language skills since infancy. He achieved head control at age 8 months, was able to sit with support at age 1 year and without support at age 18 months, and walked unaided at age 24 months. He began speaking single words at age 12 months, and simple sentences at age 4 years. In addition to difficulties walking, impaired language skills (verbal fluency and understanding) and cognitive function and difficulties with hand movements became more noticeable over time. According to physical examination, his weight, height, and head circumference were 20 kg (50th-75th centile), 110 cm (50th-75th centile), and 51 cm (50th centile), respectively. A neurologic examination indicated cerebellar dysfunction (gait ataxia, dysmetria, and dysdiadochokinesia), hyperreflexia, and mental retardation. During the examination, we observed a seizure involving eyelid myoclonia, upward rolling of the eyeballs, and head retroflexion. An electroencephalogram revealed bilaterally synchronous polyspike/spike-andwave discharges. Cranial magnetic resonance imaging examination was performed on a 1.5 T magnetic resonance unit (Intera Master, Philips Medical Systems, Best, The Netherlands). We performed T2-weighted (TR/TE ¼ 5304/110) image sequences with a slice thickness of 5 mm in the axial plane and 4 mm in the coronal plane. In addition, axial fluid attenuated inversion recovery imaging was performed. The results revealed bilateral hyperintense lesions, predominantly in the frontal cerebral white matter (Fig 1), globus pallidus (Fig 2), and dentate nuclei (Fig 3). The periventricular white matter, thalami, and brainstem were spared. We initiated treatment with lamotrigine (5 mg/kg/day), and metabolic studies were performed. On follow-up, his seizures continued, and clonazepam (0.1 mg/kg/ day) was added to the treatment to achieve better control of the eyelid myoclonia. The patient became seizure-free and responded well to treatment. On day 5 of his hospitalization, he was discharged. A month later, he presented again with seizures. Electroencephalogram findings were the same as previously. Urinary organic acid analyses (performed with gas chromatography/mass spectrometry) demonstrated a very large peak of 2-hydroxyglutaric acid.
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A. Mete et al. / Pediatric Neurology 46 (2012) 195e197
Figure 1. Axial fluid attenuated inversion recovery image reveals scattered hyperintensity of the peripheral subcortical white matter of the frontal lobe, with sparing of the periventricular white matter.
We attempted treatment with oral levetiracetam (40 mg/kg/day), riboflavin (200 mg/day), and L-carnitine (100 mg/kg per day). The patient responded with significant clinical improvement. The parents reported that the patient’s cognitive function had improved after 1 year of therapy, and that he participates in sports activities at preschool. He is able to verbalize the names of his family, and can draw some animal figures. An interictal electroencephalogram revealed no more epileptiform discharges. He has remained seizure-free for 12 months on lamotrigine, clonazepam, and levetiracetam combination therapy. Considering the laboratory and radiologic findings, the patient was diagnosed with L-2 hydroxyglutaric aciduria involving eyelid myoclonia with absences.
Discussion L-2 hydroxyglutaric aciduria is an autosomal recessive metabolic encephalopathy. It is characterized by psychomotor delay and
cerebellar and extrapyramidal signs, often associated with seizures and macrocephaly [6]. Macrocephaly is a finding that should alert clinicians to the possibility of a cerebral organic aciduria, although it is shared by several other metabolic diseases, e.g., glutaric aciduria type I and Canavan disease. However, that finding was absent in our patient. Macrocephaly occurs when the disease manifests itself before the closure of the cranial sutures, possibly as a result of edematous swelling of the cerebral hemispheres. Subsequently, resolution of the swelling followed by atrophy of the white matter may account for the absence of macrocephaly in older subjects, such as our patient. In Canavan disease, the clinical presentation and results of magnetic resonance imaging are quite different, except for subcortical leukoencephalopathy, which is much more severe and generally not associated with seizures or epileptiform abnormalities. The characteristic cranial magnetic resonance imaging findings of L-2 hydroxyglutaric aciduria consist of predominantly subcortical leukoencephalopathy, a centripetal extension of white matter involvement, bilateral nucleus dentatus lesions with variable basal ganglia involvement, and vermian and hemispheric atrophy. The periventricular white matter, thalamus, brainstem, and spinal cord are spared [5,7]. These findings of magnetic resonance imaging suggested a metabolic disorder specific for L-2 hydroxyglutaric aciduria. Our patient manifested the same magnetic resonance imaging findings as previously described in the literature for L-2 hydroxyglutaric aciduria. He had no history of an acute hypoxic event or trauma, meningitis, encephalitis, or any family history of a similar disease. The neuroradiologic features of subcortical leukoencephalopathy with involvement of the dentate nuclei and basal ganglia are rather specific, and should lead to further biochemical investigation [5,7]. A definitive diagnosis depends on the detection of L-2 hydroxyglutaric acid in urine, blood, and cerebrospinal fluid. The increased urinary excretion of L-hydroxyglutaric acid, clinical findings (seizures), electroencephalogram results, and typical magnetic resonance imaging findings in this patient established the diagnosis of L-2 hydroxyglutaric aciduria involving eyelid myoclonia with absences. Eyelid myoclonia with absences comprises a rare epileptic syndrome, characterized clinically by myoclonic jerks of the eyelids with upward deviation of the eyes (and occasionally the head), which are associated with very brief absences. Electroencephalograms reveal generalized spike-wave or polyspike-wave discharges that occur on eye closure and after intermittent photic stimulation.
Figure 2. Axial T2-weighted (a) and fluid attenuated inversion recovery (b) images indicate hyperintensity of the globi pallidi.
A. Mete et al. / Pediatric Neurology 46 (2012) 195e197
197
L-carnitine levels, valproic acid competes with glutaric acid for esterification with L-carnitine, further reducing the opportunity for the excretion of toxic glutaric acids. Thus valproic acid enhances the accumulation of toxic metabolites in these patients [11]. The second-line treatment includes ethosuximide, lamotrigine, benzodiazepines, and acetazolamide, which may be used alone or in combination with valproic acid [10]. Initially we tried monotherapy with lamotrigine, but the patient’s seizures were not controlled. Therefore, we added other antiepileptic drugs. The patient has remained seizure-free for 12 months. In conclusion, inborn errors of metabolism comprise a difficult group of disorders for the neuroradiologist and pediatric neurologist, because few good clinical and neuroradiologic criteria have been established to differentiate them. The white matter is commonly involved [12]. Laboratory tests, a thorough physical examination, and the proper use of magnetic resonance imaging can be very useful for separating these disorders, and sometimes allow for a specific diagnosis, as in the present case. Neurometabolic diseases should be considered in the differential diagnosis of all patients presenting with neuromotor developmental delay, seizures, and abnormalities of their cranial magnetic resonance imaging.
Figure 3. Coronal T2-weighted image indicates marked bilateral symmetric hyperintensity in the dentate nuclei.
In addition, rare tonic-clonic seizures may occur. The age at onset of the disorder is similar to that of typical absence epilepsy (i.e., between ages 3 and 7 years). In addition, eyelid myoclonia with absences occurs with polyspikes and 2.5-6 Hz polyspike-slow waves. However, without absence seizures it occurs with mainly polyspike discharges of brief (1-2 second) duration [8,9]. Our patient demonstrated the characteristic clinical and electroencephalographic features of eyelid myoclonia with absence episodes, including age at onset and response to treatment. However, we detected no photosensitivity and no pattern of eye-closure sensitivity on electroencephalogram. Seizure control in eyelid myoclonia with absence seizures is usually more difficult than in absence and other generalized epilepsies. Sodium valproate with either ethosuximide or occasionally clobazam appears more effective in treating this condition than if a single drug is used alone. Valproic acid monotherapy is the drug of choice for the treatment of eyelid myoclonia with absences [10]. On initial admission, a child may be suspected of manifesting metabolic disease, and therefore valproic acid is not the preferred first-line therapy. Valproic acid, which is a simple, short-chain fatty acid, causes secondary carnitine deficiency attributable to the urinary excretion of valproylcarnitine. In addition to reducing total
References [1] Szthria L, Gururaj A, Vreken P, Nork M, Lestringant G. L-2-hydroxyglutaric aciduria in two siblings. Pediatr Neurol 2002;27:141e4. [2] Topçu M, Aydin OF, Yalçinkaya C, et al. L-2-hydroxyglutaric aciduria: A report of 29 patients. Turk J Pediatr 2005;47:1e7. [3] Barth PG, Hoffmann GF, Jaeken J, et al. L-2-hydroxyglutaric aciduria: Clinical and biochemical findings in 12 patients and preliminary report on L-2hydroxyglutaric dehydrogenase. J Inherit Metab Dis 1993;16:753e61. [4] De Klerk LB, Huijmans JG, Stroink H, Robben SG, Jacobs C, Duran M. L-2hydroxyglutaric aciduria: Clinical heterogeneity versus biochemical homogeneity in a sibship. Neuropediatrics 1997;28:314e7. [5] Barbot C, Fineza I, Diogo L, et al. L-2-hydroxyglutaric aciduria: Clinical, biochemical and magnetic resonance imaging in six Portuguese pediatric patients. Brain Dev 1997;19:268e73. [6] Barth PG, Hoffmann GF, Jaeken JJ, et al. L-2-hydroxyglutaric acidemia: A novel inherited neurometabolic disorder. Ann Neurol 1992;32:66e71. [7] Topcu M, Erdem G, Saatci I, et al. Clinical and magnetic resonance imaging features of L-2-hydroxyglutaric acidemia: Report of three cases in comparison with Canavan disease. J Child Neurol 1996;11:373e7. [8] Striano S, Capovilla G, Sofia V, et al. Eyelid myoclonia with absences (Jeavons syndrome): A well-defined idiopathic generalized epilepsy syndrome or a spectrum of photosensitive conditions? Epilepsia 2009;5:15e9. [9] Giannakodimos S, Panayiotopoulos CP. Eyelid myoclonia with absences in adults: A clinical and video-EEG study. Epilepsia 1996;37:36e44. [10] Panayiotopoulos CP. Treatment of typical absence seizures and related epileptic syndromes. Paediatr Drugs 2001;3:379e403. [11] Okamura N, Ohnishi S, Shimaoka H, Norikura R, Hasegawa H. Involvement of recognition and interaction of carnitine transporter in the decrease of L-carnitine concentration induced by pivalic acid and valproic acid. Pharm Res 2006;23:1729e35. [12] Barkovich AJ. An approach to MRI of metabolic disorders in children. J Neuroradiol 2007;34:75e88.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Case Report
Eyelid Myoclonia With Absence Seizures in a Child With L-2 Hydroxyglutaric Aciduria: Findings of Magnetic Resonance Imaging Ahmet Mete MD a, *, Sedat Isikay MD b, Akif Sirikci MD a, Ayhan Ozkur MD a, Metin Bayram MD a a b
Department of Radiology, School of Medicine, Gaziantep University, Gaziantep, Turkey Department of Pediatric Neurology, School of Medicine, Gaziantep University, Gaziantep, Turkey
article information
abstract
Article history: Received 18 September 2011 Accepted 17 January 2012
L-2 hydroxyglutaric aciduria is a rare, autosomal recessively inherited metabolic disorder of organic acid metabolism. A 5-year-old boy presented with eyelid myoclonia with absences that proved difficult to control with first-line anticonvulsants. An electroencephalogram produced profoundly abnormal results, with generalized spike-and-wave discharges. The patient became seizure-free with a combination therapy of clonazepam, levetiracetam, and lamotrigine. Magnetic resonance imaging demonstrated subcortical white matter and basal ganglia alterations. Urinary organic acid analysis demonstrated increased excretion of L-2 hydroxyglutaric acid. Although rare, seizures can occur as a presenting sign of slowly progressing organic acidurias, e.g., L-2 hydroxyglutaric aciduria. Both eyelid myoclonia with absences and L-2 hydroxyglutaric aciduria comprise rare disorders. To our knowledge, this case report is the first of L-2 hydroxyglutaric aciduria presenting with symptomatic eyelid myoclonia with absences. Ó 2012 Elsevier Inc. All rights reserved.
Introduction L-2 hydroxyglutaric aciduria is a rare metabolic disorder characterized by a progressive neurologic syndrome of cerebellar and pyramidal signs, mental deterioration, tremor, and extrapyramidal signs during the first years of age. Seizures, epilepsy, and macrocephaly may constitute additional findings [1]. Metabolic disorders rarely present with seizures in isolation [2]. Seizures occur in more than 50% of patients with L-2 hydroxyglutaric aciduria, usually late in the course of the disease [3-5]. Eyelid myoclonia with absences constitutes a generalized epileptic condition clinically characterized by eyelid myoclonia with or without absence seizures, eye closure-induced electroencephalographic paroxysms, and photosensitivity. We present a 5-year-old boy who presented with eyelid myoclonia with absence seizures. He was subsequently diagnosed with L-2 hydroxyglutaric aciduria.
Case Report A 5-year-old boy was referred to us with a history of seizures during the previous 6 months, beginning with myoclonia of the eyelids. Within 2 months, the seizures worsened, and occurred many times a day. He was born at term after an uneventful pregnancy to nonconsanguineous healthy parents. Delivery was * Communications should be addressed to: Dr. Mete; Department of Radiology; School of Medicine; Gaziantep University; Sahinbey, 27310 Gaziantep, Turkey. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2012.01.008
normal. His birth weight was 3500 g (25th-50th centile), his height was 53 cm (25th-50th centile), and his head circumference was 34.5 cm (25th-50th centile). He was his parents’ first child. They described developmental delay in his motor, social, and language skills since infancy. He achieved head control at age 8 months, was able to sit with support at age 1 year and without support at age 18 months, and walked unaided at age 24 months. He began speaking single words at age 12 months, and simple sentences at age 4 years. In addition to difficulties walking, impaired language skills (verbal fluency and understanding) and cognitive function and difficulties with hand movements became more noticeable over time. According to physical examination, his weight, height, and head circumference were 20 kg (50th-75th centile), 110 cm (50th-75th centile), and 51 cm (50th centile), respectively. A neurologic examination indicated cerebellar dysfunction (gait ataxia, dysmetria, and dysdiadochokinesia), hyperreflexia, and mental retardation. During the examination, we observed a seizure involving eyelid myoclonia, upward rolling of the eyeballs, and head retroflexion. An electroencephalogram revealed bilaterally synchronous polyspike/spike-andwave discharges. Cranial magnetic resonance imaging examination was performed on a 1.5 T magnetic resonance unit (Intera Master, Philips Medical Systems, Best, The Netherlands). We performed T2-weighted (TR/TE ¼ 5304/110) image sequences with a slice thickness of 5 mm in the axial plane and 4 mm in the coronal plane. In addition, axial fluid attenuated inversion recovery imaging was performed. The results revealed bilateral hyperintense lesions, predominantly in the frontal cerebral white matter (Fig 1), globus pallidus (Fig 2), and dentate nuclei (Fig 3). The periventricular white matter, thalami, and brainstem were spared. We initiated treatment with lamotrigine (5 mg/kg/day), and metabolic studies were performed. On follow-up, his seizures continued, and clonazepam (0.1 mg/kg/ day) was added to the treatment to achieve better control of the eyelid myoclonia. The patient became seizure-free and responded well to treatment. On day 5 of his hospitalization, he was discharged. A month later, he presented again with seizures. Electroencephalogram findings were the same as previously. Urinary organic acid analyses (performed with gas chromatography/mass spectrometry) demonstrated a very large peak of 2-hydroxyglutaric acid.
196
A. Mete et al. / Pediatric Neurology 46 (2012) 195e197
Figure 1. Axial fluid attenuated inversion recovery image reveals scattered hyperintensity of the peripheral subcortical white matter of the frontal lobe, with sparing of the periventricular white matter.
We attempted treatment with oral levetiracetam (40 mg/kg/day), riboflavin (200 mg/day), and L-carnitine (100 mg/kg per day). The patient responded with significant clinical improvement. The parents reported that the patient’s cognitive function had improved after 1 year of therapy, and that he participates in sports activities at preschool. He is able to verbalize the names of his family, and can draw some animal figures. An interictal electroencephalogram revealed no more epileptiform discharges. He has remained seizure-free for 12 months on lamotrigine, clonazepam, and levetiracetam combination therapy. Considering the laboratory and radiologic findings, the patient was diagnosed with L-2 hydroxyglutaric aciduria involving eyelid myoclonia with absences.
Discussion L-2 hydroxyglutaric aciduria is an autosomal recessive metabolic encephalopathy. It is characterized by psychomotor delay and
cerebellar and extrapyramidal signs, often associated with seizures and macrocephaly [6]. Macrocephaly is a finding that should alert clinicians to the possibility of a cerebral organic aciduria, although it is shared by several other metabolic diseases, e.g., glutaric aciduria type I and Canavan disease. However, that finding was absent in our patient. Macrocephaly occurs when the disease manifests itself before the closure of the cranial sutures, possibly as a result of edematous swelling of the cerebral hemispheres. Subsequently, resolution of the swelling followed by atrophy of the white matter may account for the absence of macrocephaly in older subjects, such as our patient. In Canavan disease, the clinical presentation and results of magnetic resonance imaging are quite different, except for subcortical leukoencephalopathy, which is much more severe and generally not associated with seizures or epileptiform abnormalities. The characteristic cranial magnetic resonance imaging findings of L-2 hydroxyglutaric aciduria consist of predominantly subcortical leukoencephalopathy, a centripetal extension of white matter involvement, bilateral nucleus dentatus lesions with variable basal ganglia involvement, and vermian and hemispheric atrophy. The periventricular white matter, thalamus, brainstem, and spinal cord are spared [5,7]. These findings of magnetic resonance imaging suggested a metabolic disorder specific for L-2 hydroxyglutaric aciduria. Our patient manifested the same magnetic resonance imaging findings as previously described in the literature for L-2 hydroxyglutaric aciduria. He had no history of an acute hypoxic event or trauma, meningitis, encephalitis, or any family history of a similar disease. The neuroradiologic features of subcortical leukoencephalopathy with involvement of the dentate nuclei and basal ganglia are rather specific, and should lead to further biochemical investigation [5,7]. A definitive diagnosis depends on the detection of L-2 hydroxyglutaric acid in urine, blood, and cerebrospinal fluid. The increased urinary excretion of L-hydroxyglutaric acid, clinical findings (seizures), electroencephalogram results, and typical magnetic resonance imaging findings in this patient established the diagnosis of L-2 hydroxyglutaric aciduria involving eyelid myoclonia with absences. Eyelid myoclonia with absences comprises a rare epileptic syndrome, characterized clinically by myoclonic jerks of the eyelids with upward deviation of the eyes (and occasionally the head), which are associated with very brief absences. Electroencephalograms reveal generalized spike-wave or polyspike-wave discharges that occur on eye closure and after intermittent photic stimulation.
Figure 2. Axial T2-weighted (a) and fluid attenuated inversion recovery (b) images indicate hyperintensity of the globi pallidi.
A. Mete et al. / Pediatric Neurology 46 (2012) 195e197
197
L-carnitine levels, valproic acid competes with glutaric acid for esterification with L-carnitine, further reducing the opportunity for the excretion of toxic glutaric acids. Thus valproic acid enhances the accumulation of toxic metabolites in these patients [11]. The second-line treatment includes ethosuximide, lamotrigine, benzodiazepines, and acetazolamide, which may be used alone or in combination with valproic acid [10]. Initially we tried monotherapy with lamotrigine, but the patient’s seizures were not controlled. Therefore, we added other antiepileptic drugs. The patient has remained seizure-free for 12 months. In conclusion, inborn errors of metabolism comprise a difficult group of disorders for the neuroradiologist and pediatric neurologist, because few good clinical and neuroradiologic criteria have been established to differentiate them. The white matter is commonly involved [12]. Laboratory tests, a thorough physical examination, and the proper use of magnetic resonance imaging can be very useful for separating these disorders, and sometimes allow for a specific diagnosis, as in the present case. Neurometabolic diseases should be considered in the differential diagnosis of all patients presenting with neuromotor developmental delay, seizures, and abnormalities of their cranial magnetic resonance imaging.
Figure 3. Coronal T2-weighted image indicates marked bilateral symmetric hyperintensity in the dentate nuclei.
In addition, rare tonic-clonic seizures may occur. The age at onset of the disorder is similar to that of typical absence epilepsy (i.e., between ages 3 and 7 years). In addition, eyelid myoclonia with absences occurs with polyspikes and 2.5-6 Hz polyspike-slow waves. However, without absence seizures it occurs with mainly polyspike discharges of brief (1-2 second) duration [8,9]. Our patient demonstrated the characteristic clinical and electroencephalographic features of eyelid myoclonia with absence episodes, including age at onset and response to treatment. However, we detected no photosensitivity and no pattern of eye-closure sensitivity on electroencephalogram. Seizure control in eyelid myoclonia with absence seizures is usually more difficult than in absence and other generalized epilepsies. Sodium valproate with either ethosuximide or occasionally clobazam appears more effective in treating this condition than if a single drug is used alone. Valproic acid monotherapy is the drug of choice for the treatment of eyelid myoclonia with absences [10]. On initial admission, a child may be suspected of manifesting metabolic disease, and therefore valproic acid is not the preferred first-line therapy. Valproic acid, which is a simple, short-chain fatty acid, causes secondary carnitine deficiency attributable to the urinary excretion of valproylcarnitine. In addition to reducing total
References [1] Szthria L, Gururaj A, Vreken P, Nork M, Lestringant G. L-2-hydroxyglutaric aciduria in two siblings. Pediatr Neurol 2002;27:141e4. [2] Topçu M, Aydin OF, Yalçinkaya C, et al. L-2-hydroxyglutaric aciduria: A report of 29 patients. Turk J Pediatr 2005;47:1e7. [3] Barth PG, Hoffmann GF, Jaeken J, et al. L-2-hydroxyglutaric aciduria: Clinical and biochemical findings in 12 patients and preliminary report on L-2hydroxyglutaric dehydrogenase. J Inherit Metab Dis 1993;16:753e61. [4] De Klerk LB, Huijmans JG, Stroink H, Robben SG, Jacobs C, Duran M. L-2hydroxyglutaric aciduria: Clinical heterogeneity versus biochemical homogeneity in a sibship. Neuropediatrics 1997;28:314e7. [5] Barbot C, Fineza I, Diogo L, et al. L-2-hydroxyglutaric aciduria: Clinical, biochemical and magnetic resonance imaging in six Portuguese pediatric patients. Brain Dev 1997;19:268e73. [6] Barth PG, Hoffmann GF, Jaeken JJ, et al. L-2-hydroxyglutaric acidemia: A novel inherited neurometabolic disorder. Ann Neurol 1992;32:66e71. [7] Topcu M, Erdem G, Saatci I, et al. Clinical and magnetic resonance imaging features of L-2-hydroxyglutaric acidemia: Report of three cases in comparison with Canavan disease. J Child Neurol 1996;11:373e7. [8] Striano S, Capovilla G, Sofia V, et al. Eyelid myoclonia with absences (Jeavons syndrome): A well-defined idiopathic generalized epilepsy syndrome or a spectrum of photosensitive conditions? Epilepsia 2009;5:15e9. [9] Giannakodimos S, Panayiotopoulos CP. Eyelid myoclonia with absences in adults: A clinical and video-EEG study. Epilepsia 1996;37:36e44. [10] Panayiotopoulos CP. Treatment of typical absence seizures and related epileptic syndromes. Paediatr Drugs 2001;3:379e403. [11] Okamura N, Ohnishi S, Shimaoka H, Norikura R, Hasegawa H. Involvement of recognition and interaction of carnitine transporter in the decrease of L-carnitine concentration induced by pivalic acid and valproic acid. Pharm Res 2006;23:1729e35. [12] Barkovich AJ. An approach to MRI of metabolic disorders in children. J Neuroradiol 2007;34:75e88.