A Case of Acute Bilateral Ptosis: SURF-1 Mutation/Akut Bilateral Pitozisle Basvuran Olgu: SURF-1 Mutasyonu.
Anahtar Kelimeler: Pitozis, SURF-1 mutasyonu, mitokondriyal hastalik
A 14-month-old girl presented with a one-week history of bilateral ptosis without fluctuations in the intensity and distribution over time. Development stages were normal with no history of seizure, trauma or intoxication. On neurologic examination, bilateral ptosis was present, but eye movements, pupillary light reflexes, fundus and other cranial nerve functions were normal. Toxic, infectious, and metabolic causes that could affect the brainstem were considered in the differential diagnosis. Laboratory investigations revealed elevated serum lactate (31 mg/dL; reference values: 8-22 mg/dL) with normal pyruvate levels (0.37 mg/dL; reference values: 0.3-0.9 mg/dL). Cerebrospinal fluid (CSF) analysis demonstrated elevated lactate level (32 mg/dL; reference values: 5-19 mg/dL) with normal protein and glucose levels. Brain magnetic resonance imaging (MRI) showed bilateral and symmetrical non-enhancing lesions with restricted diffusion in the olives, dorsal brainstem tracts, substantia nigra, periaqueductal gray matter and subthalamic nuclei (Figure 1). The MRI pattern was suggestive for cytochrome-c oxidase deficiency with SURF-1 mutation.
She was substituted with coenzyme [Q.sub.10] (100 mg/day), carnitine (1 g/day) and high-dose multivitamin treatment (100 mg/day riboflavin, 100 mg/day thiamine, 10 mg/day biotin). One month after the initial presentation, recovery of ptosis was recognized. Molecular analyses revealed a homozygous c.518_538 (p.V173GfsX) deletion in SURF-1. After 7 months of follow-up, she presented with ataxic gait, confusion, nystagmus, and ptosis. Repeated brain MRI showed additional bilateral and symmetric lesions in the medial cerebellar hemispheres and superior cerebellar peduncles with restricted diffusion (Figure 2). It was learned from the family that they could not access drugs for 2 weeks.
Bilateral subthalamic nuclei involvement as T2 and fluid-attenuated inversion recovery (FLAIR) hyperintense signal abnormality is a very common neuroimaging finding in Leigh syndrome (LS) with underlying SURF-1 mutations. The additional findings include T1-hypointense and T2 and FLAIR hyperintense signal abnormalities in the inferior olivary nuclei, inferior cerebellar peduncles, central tegmental tracts, reticular formation in the dorsal pons and periaqueductal gray matter in the midbrain (1,2). Our patient had progressive neurologic disease, signs and symptoms of brainstem and/or basal ganglia disease, raised lactate levels in blood and/or CSF and characteristic features of LS on neuroimaging (hyperintense lesions on T2-weighted MRI) (3,4).
Though LS is widely known to have a tendency to follow the course of progressive deterioration, we are acknowledge that several pathway-specific compounds such as thiamine and coenzyme [Q.sub.10] have already been shown to be beneficial in patients. Our patient has already shown remarkable clinical improvement after management with high-dose vitamin and coenzyme [Q.sub.10] treatment at the first attack, but it was known that spontaneous recovery could be misinterpreted as a positive therapeutic response as a result of the fluctuations of disease severity (5). A high index of suspicion combined with a knowledge of ocular manifestations and the correlation of typical imaging features can help make the correct diagnosis.
Informed Consent: Informed consent was obtained from patient's parent.
Peer-review: Internally peer-reviewed.
Concept: O.D., Design: O.D., C.G.S., Data Collection or Processing: O.D., Analysis or Interpretation: O.D., D.Y., M.K., K.K.O., B.T., Literature Search: O.D., Writing: O.D., M.K.
Conflict of Interest and Financial Disclosure: The authors whose names are listed above certify that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject master or materials discussed in this manuscript. The genetic analyses was tested by Damagen laboratory.
(1.) Rossi A, Biancheri R, Bruno C, Di Rocco M, Calvi A, Pessagno A, Tortori-Donati P. Leigh Syndrome with COX deficiency and SURF1 gene mutations: MR imaging findings. AJNR Am J Neuroradiol 2003;24:1188-1191.
(2.) Bosemani T, Anghelescu C, Boltshauser E, Hoon AH Jr, Pearl PL, Craiu D, Johnston MV, Huisman TA, Poretti A. Subthalamic nucleus involvement in children: a neuroimaging pattern-recognition approach. Eur J Paediatr Neurol 2014;18:249-256.
(3.) Ogawa E, Shimura M, Fushimi T, Tajika M, Ichimoto K, Matsunaga A, Tsuruoka T, Ishige M, Fuchigami T, Yamazaki T, Mori M, Kohda M, Kishita Y, Okazaki Y, Takahashi S, Ohtake A, Murayama K. Clinical validity of biochemical and molecular analysis in diagnosing Leigh syndrome: a study of 106 Japanese patients. J Inherit Metab Dis 2017;40:685-693.
(4.) Rahman S, Blok RB, Dahl HH, Danks DM, Kirby DM, Chow CW, Christodoulou J, Thorburn DR. Leigh syndrome: clinical features and biochemical and DNA abnormalities. Ann Neurol 1996;39:343-351.
(5.) Pfeffer G, Horvath R, Klopstock T, Mootha VK, Suomalainen A, Koene S, Hirano M, Zeviani M, Bindoff LA, Yu-Wai-Man P, Hanna M, Carelli V McFarland R, Majamaa K, Turnbull DM, Smeitink J, Chinnery PF. New treatments for mitochondrial disease-no time to drop our standards. Nat Rev Neurol 2013;9:474-481.
Ozge Dedeoglu (1), Deniz Yuksel (1), Cigdem Genc Sel (1), Mustafa Kilic (2), Kader Karli Oguz (3), Beril Talim (4)
(1) Dr. Sami Ulus Children's Hospital, Clinic of Pediatric Neurology, Ankara, Turkey
(2) Dr. Sami Ulus Children's Hospital, Clinic of Metabolism, Ankara, Turkey
(3) Hacettepe University Faculty of Medicine, Department of Radiology, Ankara, Turkey
(4) Hacettepe University Faculty of Medicine, Department of Pediatrics, Pathology Unit, Ankara, Turkey
Address for Correspondence/Yazisma Adresi: Ozge Dedeoglu MD, Dr. Sami Ulus Children's Hospital, Clinic of Pediatric Neurology, Ankara, Turkey Phone: +90 312 305 60 00 E-mail: email@example.com ORCID ID: orcid.org/0000-0002-7492-5255
Received/Gelis Tarihi: 11.08.2017 Accepted/Kabul Tarihi: 05.12.2017
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||Images in Clinical Neurology / Klinik Gorunum|
|Author:||Dedeoglu, Ozge; Yuksel, Deniz; Sel, Cigdem Genc; Kilic, Mustafa; Oguz, Kader Karli; Talim, Beril|
|Publication:||Turkish Journal of Neurology|
|Article Type:||Letter to the editor|
|Date:||Mar 1, 2018|
|Previous Article:||Dysarthria-clumsy Hand Syndrome due to Rostral Pontine Infarct Rostral Pons Infarktina Bagli Gelisen Dizartri-Beceriksiz El Sendromu.|
|Next Article:||Cerebral Venous Sinus Thrombosis Presenting as Cortical Blindness/Kortikal Korluk ile Prezente Olan Serebral Venoz Sinus Trombozu.|