A novel nonsense mutation in the TYMP gene causing MNGIE with multiple intracranial hemorrhages on brain MRI
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LETTER TO THE EDITOR
A novel nonsense mutation in the TYMP gene causing MNGIE with multiple intracranial hemorrhages on brain MRI Zheng Jiang 1 & Bi Zhao 1 & Hui-fang Shang 1
&
Wei Song 1
Received: 20 July 2020 / Accepted: 11 November 2020 # Fondazione Società Italiana di Neurologia 2020
Dear Editor, Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE; OMIM 603041) is a rare autosomal recessive mitochondrial disorder caused by mutations in the TYMP gene encoding thymidine phosphorylase (TP) [1]. TYMP mutations account for reduced TP activity, resulting in remarkably elevated plasma nucleosides (thymidine and deoxyuridine). The subsequent unbalanced nucleotide pool leads to disturbances in mitochondrial DNA (mtDNA) replication and ultimately mitochondrial failure [2]. Typical clinical manifestations of MNGIE include severe gastrointestinal dysmotility, cachexia, ptosis and external ophthalmoplegia, sensorimotor neuropathy, and leukoencephalopathy. Onset often insidiously occurs between the first and second decade [3]. The extensive white matter involvement is the imaging hallmark of MNGIE [4]. Given the substantial complexity in its features, MNGIE is easily misdiagnosed as other disease entities and insufficiently treated for long periods. Here, we report a case with MNGIE that had typical and previously unreported manifestations caused by a novel homozygous nonsense mutation in exon 1 of the TYMP gene. We fully considered and excluded possible differential diagnoses before a final diagnosis was made.
Case description A 24-year-old woman presented to the gastroenterology clinic, complaining of recurrent vomiting, diarrhea, and pseudoZheng Jiang and Bi Zhao contributed equally to this work. * Hui-fang Shang [email protected] * Wei Song [email protected] 1
Department of Neurology, West China Hospital, Sichuan University, Wai Nan Guo Xue Xiang 37#, Chengdu 610041, Sichuan, China
intestinal obstruction for 5 years, accompanied by progressive limb weakness and weight loss. When examined, she was noted to have bilateral ptosis and ophthalmoplegia but denied diplopia or fluctuating weakness. Upper and lower gastrointestinal endoscopy coupled with computed tomography of the chest, abdomen, and pelvis were unremarkable. The patient was admitted to the neurology department. During the hospitalization, the patient was transferred to the neurologic intensive care unit for further symptom management and supportive care owing to aspiration pneumonia and worsening malnutrition. Her family history was unremarkable. She denied any history of gluten intolerance, toxic exposure, or drug addiction. Physical examination disclosed short stature and severe cachexia (Fig. 1a). Her height was 150 cm, and weight 25 kg, with a body mass index of 11.1. Neurological examination revealed moderate ptosis (Fig. 1b) and severe restriction in all ranges of extraocular movements bilaterally, mild bilateral sensorineural hearing loss, generalized muscle atrophy, decreased muscle tone and muscle strength in the upper and lowe
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