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Vanishing white matter leukodystrophy a rare case report

Yıl 2013, Cilt: 48 Sayı: 1, 78 - 79, 01.03.2013

Öz

To the Editor Vanishing white matter VWM leukoencephalopathy is an autosomal recessive disease which is also known as 39; 39;childhood ataxia with central nervous system hypomyelinization rdquo; It was defined by Van der Knaap et al 1 in 1977 for the first time The most common type is manifested by cerebellar ataxia spasticity and mental regression in the early childhood 2 It is known that stress is a significant factor in the disease onset and clinical exacerbations 3 The mutation which causes the disease involves the mutations in the five genes ElF2B1 ElF2B2 ElF2B3 ElF2B4 ElF2B5 coding eIF2B which is the eukariotic translation initiation factor In time it has been recognized that this disease which was initially described for the chidlhood and which has a wide range of phenotypic variability can affect patients at any age 1 4 We wanted to present this patient because he was the first genetically proved case in Turkey and we wished to emphasize that this rare disease should be considered in the differential diagnosis of neurodegenerative diseases in the childhood Our patient who was a 8 year old male patient presented because of gradually increasing loss of motor abilities following an upper respiratory tract infection with fevet at the age of four for the first time The family who recognized his muscle weakness observed that the child had unsteady gait and that this increased in time His medical history revealed that his perinatal history and neurological development until the age of one were normal The mother and father were third degree relatives and familial history was found to be normal On physical examination the height and weight were found to be normal visual and auditory problems were absent and cognitive functions were compatible with his age Our patient had no dysmorphic charactersitic Ataxia intentional tremor in both upper extremities and dysdiyadochinesia were found on neurological examination Diffuse hypotonia and decrease in muscle strenght in all extremities were found Muscle strength was found to be 4 5 in the left arm right arm and left leg and 3 5 in the right leg Both Achilles reflexes and patella reflexes were found to be increased Clonus and Babinsky were found to be positive in both lower extremities Fundoscopic examination was found to be normal Examination of the other systems was found to be normal Regular screenings and metabolic tests were found to be normal in the laboratory findings On magnetic resonance imaging MRI of the brain diffusely increased density in the white matter in FLAIR sequences and locally cystic areas with the same intensity as the cerebrospinal fluid were observed VWM disease was considered with the clinical findings and brain MR findings in the patient in whom genetic analysis was planned Genetic mutation analysis revealed homozygous mutation in the EIF2B5: 943C gt;G DNA R315G protein gene The mother and father were found to be carriers for the same mutation Thus the diagnosis of VWM disease was confirmed Our patient is now receiving physiotherapy and individual education in a special education center Worsening in the acute motor functions was observed for two times in 2010 and 2011 Our patient had fever during both of these worsening attacks In the follow up the intellectual functions were found to be retarded for his age No auditory or visual problem developed The patient who had an articulation problem while speaking did never lost comprehensibility in the communication with the people around The patient whose muscle weakness increased is not able to perform daily activities by himself for the time being The disease is manifested by cerebellar ataxia and more rarely with spasticity The consciousness is usually preserved In the advanced period vision loss with optic atrophy is among the findings described 1 Vermeulen et al 3 emphasized that stress was an important factor both in the onset of the disease and clinical exacerbations Other factors which speed the progression include infections with fever cranial traumas and fear spells Outside these periods the disease has a slow clinical course but mortality is inevitable 2 3 It was learned that our patient had an upper respiratory tract infection with fever at the time the first symptoms appeared In the early childhood brain MRI is the most strong supporting tool for the diagnosis On MRI progressive decrease in volume and cystic degeneration are observed in the white matter MR spectroscopy reveals progressive decrease in all metabolites which can be tested Cerebellar and brain stem involvement is observed in the lost white matter In the later stages cerebral and cerebellar atrophy is observed 1 2 Cortical grey matter is always preserved 1 On cranial MRI of our patient enlargement in the lateral ventricles Figure 1 and cerebellar atrophy in the T2 weighted sections diffusely increased intensity in the white matter and cystic areas with the same intensity as the cerebrospinal fluid in FLAIR sequences were observed For the time being there is no treatment for the disease except for supportive treatment which is given to increase the quality of life In time it has been recognized that this disease which was initially described for the chidlhood and which has a wide range of phenotypic variability can affect patients at any age 1 5 In the prenatal form of the disease decreased fetal movements oligohydramniosis primary microcephaly growth retardation congenital contractures renal hypoplasia hepato splenomegaly pancreatitis cataract ovarian dysgenesis and leukoencephalopathy may be observed 6 Conclusively vanishing white matter disease is a rare genetic disease In the diagnosis a history of discontinuation and regression of motor functions which start in the childhood progressive ataxia spasticity and intermittent worsening attacks is important Mutation analysis which is performed as a result of the findings observed on cranial MR confirms the diagnosis Early diagnosis is very important in terms of genetic counseling and protecting the patient from the factors which worsen the disease Researches for the unknown molecular mechanisms of this disease which has a wide clinical spectrum are continuing We wanted this patient who was the first genetically confirmed case in our country to remind physicans to consider this disease in the differential diagnosis in patients presenting with motor retardation Ad shy;dress for Cor shy;res shy;pon shy;den shy;ce: Serhat Güler MD Bezmialem Foundation University Medical Faculty Division of Pediatric Neurology İstanbul Turkey E mail: serhatguler@hotmail com Re shy;cei shy;ved: 06 30 2012 Ac shy;cep shy;ted: 11 15 2012 References 1 Bugiani M Boor I Powers JM Scheper GC van der Knaap MS Leukoencephalopathy with vanishing white matter: a review J Neuropathol Exp Neurol 2010; 69 10 : 987 986 2 van der Knaap MS Kamphorst W Barth PG Kraaijeveld CL Gut E Valk J Phenotypicvariation in leukoencephalopathy with vanishing white matter Neurology 1998; 51: 540 ndash;547 3 Vermeulen G Seidl R Mercimek Mahmutoglu S Rotteveel JJ Scheper GC van der Knaap MS Fright is a provoking factor in vanishing white matter disease Ann Neurol 2005; 57 4 : 560 563 4 van der Knaap MS Leegwater PA Könst AA Visser A Naidu S Oudejans CB Schutgens RB Pronk JC Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter Ann Neurol 2002; 51 2 : 264 270 5 van der Knaap MS Leegwater PA van Berkel CG Brenner C Storey E Di Rocco M Salvi F Pronk JC Arg113His mutation in eIF2Bepsilon as cause of leukoencephalopathy in adults Neurology 2004; 62 9 : 1598 600 6 van der Knaap MS van Berkel CG Herms J van Coster R Baethmann M Naidu S Boltshauser E Willemsen MA Plecko B Hoffmann GF Proud CG Scheper GC Pronk JC eIF2B related disorders: antenatal onset and involvement of multiple organs Am J Hum Genet 2003; 73: 1199 207

Kaynakça

  • Bugiani M, Boor I, Powers JM, Scheper GC, van der Knaap MS. Leukoencephalopathy with vanishing white matter: a review. J Neuropathol Exp Neurol 2010; 69(10): 987-6. van der Knaap MS, Kamphorst W, Barth PG, Kraaijeveld CL, Gut E, Valk J. Phenotypicvariation in leukoencephalopathy with vanishing white matter . Neurology 1998; 51: 540–7.
  • Vermeulen G, Seidl R, Mercimek-Mahmutoglu S, Rotteveel JJ, Scheper GC, van der Knaap MS. Fright is a provoking factor in vanishing white matter disease. Ann Neurol 2005; 57(4): 560-3. van der Knaap MS, Leegwater PA, Könst AA, et al. Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter. Ann Neurol 2002; 51(2): 264van der Knaap MS, Leegwater PA, van Berkel CG, et al. Arg113His mutation in eIF2Bepsilon as cause of leukoencephalopathy in adults. Neurology 2004; 62(9): 1598-600. van der Knaap MS, van Berkel CG, Herms J, et al. eIF2B-related disorders: antenatal onset and involvement of multiple organs. Am J Hum Genet 2003; 73: 1199-207. 79 Türk Ped Arfl 2013; 48: 78-9 Turk Arch Ped 2013; 48: 78-9 Güler ve ark.
  • Kaybolan beyaz madde hastalığı; nadir bir olgu / Vanishing white matter leukodystrophy, a rare case report

Kaybolan beyaz madde hastalığı; nadir bir olgu

Yıl 2013, Cilt: 48 Sayı: 1, 78 - 79, 01.03.2013

Öz

Kaybolan beyaz madde (vanishing white matter, VWM) lökoansefalopatisi ''merkezi sinir sistemi hipomiyelinizasyonu ile seyreden çocukluk çağı ataksisi'' olarak da bilinen otozomal çekinik geçişli bir hastalıktır. İlk defa 1997 yılında Van der Knaap ve ark. (1) tarafından tanımlanmıştır. En sık görülen şekli erken çocukluk döneminde serebellar ataksi, spastite ve zeka gerilemesi ile karşımıza gelir (2). Stresin hastalığın başlangıcında ve klinik alevlenmelerde, önemli bir etmen olduğu bilinmektedir (3). Hastalığa neden olan mutasyon ökaryotik translasyon başlangıç etmeni olan eIF2B'yi kodlayan toplam beş gendeki (ElF2B1,ElF2B2,ElF2B3,ElF2B4,ElF2B5) mutasyonları içermektedir. Başlangıçta çocukluk çağı için tanımlanan ve son derece geniş bir fenotipik değişkenliğe sahip bu hastalığın gün geçtikçe her yaşı etkileyebileceği görülmüştür (1,4). Nadir görülen bu hastalığın Türkiye'de ilk genetiği kanıtlanan olgu olması ve yaş grubu için nörodejenaratif hastalıklar içinde ayırıcı tanıda akla gelmesini vurgulamak için bu hastayı sunmayı uygun gördük.

Kaynakça

  • Bugiani M, Boor I, Powers JM, Scheper GC, van der Knaap MS. Leukoencephalopathy with vanishing white matter: a review. J Neuropathol Exp Neurol 2010; 69(10): 987-6. van der Knaap MS, Kamphorst W, Barth PG, Kraaijeveld CL, Gut E, Valk J. Phenotypicvariation in leukoencephalopathy with vanishing white matter . Neurology 1998; 51: 540–7.
  • Vermeulen G, Seidl R, Mercimek-Mahmutoglu S, Rotteveel JJ, Scheper GC, van der Knaap MS. Fright is a provoking factor in vanishing white matter disease. Ann Neurol 2005; 57(4): 560-3. van der Knaap MS, Leegwater PA, Könst AA, et al. Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter. Ann Neurol 2002; 51(2): 264van der Knaap MS, Leegwater PA, van Berkel CG, et al. Arg113His mutation in eIF2Bepsilon as cause of leukoencephalopathy in adults. Neurology 2004; 62(9): 1598-600. van der Knaap MS, van Berkel CG, Herms J, et al. eIF2B-related disorders: antenatal onset and involvement of multiple organs. Am J Hum Genet 2003; 73: 1199-207. 79 Türk Ped Arfl 2013; 48: 78-9 Turk Arch Ped 2013; 48: 78-9 Güler ve ark.
  • Kaybolan beyaz madde hastalığı; nadir bir olgu / Vanishing white matter leukodystrophy, a rare case report
Toplam 3 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Editöre Mektup
Yazarlar

Serhat Güler Bu kişi benim

Adnan Yüksel Bu kişi benim

Akın İşcan Bu kişi benim

İlhan Işık Bu kişi benim

Burak Tatlı Bu kişi benim

Yayımlanma Tarihi 1 Mart 2013
Yayımlandığı Sayı Yıl 2013 Cilt: 48 Sayı: 1

Kaynak Göster

APA Güler, S., Yüksel, A., İşcan, A., Işık, İ., vd. (2013). Kaybolan beyaz madde hastalığı; nadir bir olgu. Türk Pediatri Arşivi, 48(1), 78-79.
AMA Güler S, Yüksel A, İşcan A, Işık İ, Tatlı B. Kaybolan beyaz madde hastalığı; nadir bir olgu. Türk Pediatri Arşivi. Mart 2013;48(1):78-79.
Chicago Güler, Serhat, Adnan Yüksel, Akın İşcan, İlhan Işık, ve Burak Tatlı. “Kaybolan Beyaz Madde hastalığı; Nadir Bir Olgu”. Türk Pediatri Arşivi 48, sy. 1 (Mart 2013): 78-79.
EndNote Güler S, Yüksel A, İşcan A, Işık İ, Tatlı B (01 Mart 2013) Kaybolan beyaz madde hastalığı; nadir bir olgu. Türk Pediatri Arşivi 48 1 78–79.
IEEE S. Güler, A. Yüksel, A. İşcan, İ. Işık, ve B. Tatlı, “Kaybolan beyaz madde hastalığı; nadir bir olgu”, Türk Pediatri Arşivi, c. 48, sy. 1, ss. 78–79, 2013.
ISNAD Güler, Serhat vd. “Kaybolan Beyaz Madde hastalığı; Nadir Bir Olgu”. Türk Pediatri Arşivi 48/1 (Mart 2013), 78-79.
JAMA Güler S, Yüksel A, İşcan A, Işık İ, Tatlı B. Kaybolan beyaz madde hastalığı; nadir bir olgu. Türk Pediatri Arşivi. 2013;48:78–79.
MLA Güler, Serhat vd. “Kaybolan Beyaz Madde hastalığı; Nadir Bir Olgu”. Türk Pediatri Arşivi, c. 48, sy. 1, 2013, ss. 78-79.
Vancouver Güler S, Yüksel A, İşcan A, Işık İ, Tatlı B. Kaybolan beyaz madde hastalığı; nadir bir olgu. Türk Pediatri Arşivi. 2013;48(1):78-9.