Elsevier

Pediatric Neurology

Volume 32, Issue 5, May 2005, Pages 334-340
Pediatric Neurology

Case report
Atypical Presentations of Leigh Syndrome: A Case Series and Review

https://doi.org/10.1016/j.pediatrneurol.2004.12.009Get rights and content

Patients with Leigh syndrome classically present in early childhood with developmental regression, ataxia, and hypotonia with subsequent respiratory and brainstem dysfunction. However, the clinical presentation can be highly variable. This report presents five cases of Leigh syndrome with atypical presentations. The first patient is a 17-month-old female who presented with progressive limb weakness diagnosed as Guillain-Barré syndrome. Postmortem examination demonstrated Leigh syndrome confined to the spinal cord. The case series then describes two sisters one of whom presented at 11 years of age with central respiratory failure and encephalopathy. Her 15-year-old sister presented with a progressive diplegia. The fourth patient presented with bronchiolitis and apnea at 3 months of age due to bilateral brainstem lesions. Her second cousin presented at 6 months of age with hypotonia, blindness, and tonic seizures. All patients had laboratory and radiologic findings consistent with Leigh syndrome. Evidence of spinal cord involvement was observed on magnetic resonance imaging in four of the five patients. Leigh syndrome can involve any level of the neuroaxis, resulting in a wide variety of presentations. Many atypical variants are observed, of which clinicians should be aware. Evidence of brainstem or spinal cord involvement should also be sought in patients with Leigh syndrome

Introduction

Leigh syndrome (subacute necrotizing encephalomyelopathy) is a heterogenous neurologic disease that results from a disorder in the respiratory chain production of adenosine triphosphate within the mitochondria of affected cells. First described in 1951 [1], Leigh syndrome is a disorder that affects primarily infants and young children. The classical presentation is of an infant who presents with central hypotonia, developmental regression or arrest, and signs of brainstem or basal ganglia involvement which manifests as ophthalmoplegia, respiratory and bulbar dysfunction, and ataxia [2]. Diagnosis is usually confirmed by radiologic or pathologic evidence of symmetric lesions affecting the basal ganglia, brainstem, and subthalamic nuclei [3].

The clinical presentation of Leigh syndrome however, can be highly variable. This case series describes five patients with Leigh syndrome who had atypical presentations.

Section snippets

Methods

Databases belonging to the Stollery Children’s Hospital Departments of Pediatric Neurology and Medical Genetics were reviewed for all patients who were diagnosed with or suspected of having Leigh syndrome. In all, 27 patients were identified. All medical and genetic charts and available radiologic studies were reviewed to confirm that the patients met diagnostic criteria for Leigh syndrome as set forth by Rahman et al. [4]. The patients had to have (1) progressive neurologic disease with motor

Discussion

Since Leigh’s initial case report in 1951, Leigh syndrome remains an uncommon disorder. Clinical manifestations can be highly variable, making diagnosis of the disorder difficult. There are no specific markers for the disorder, and elevations in serum or cerebrospinal fluid lactate are not always present. Often the diagnosis is made only after computed tomography or magnetic resonance imaging is performed.

Leigh syndrome can be divided into both infantile and juvenile forms [5]. The infantile

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  • Leigh syndrome caused by mitochondrial DNA-maintenance defects revealed by whole exome sequencing

    2019, Mitochondrion
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    Our patients have the cardinal features of LS associated with some classical clinical features of disorders of mtDNA maintenance such as PEO, encephalomyopathy or hepatic dysfunction with genetic evidences of mtDNA large-scale rearrangements (mtDNA multiple deletions) or reduction of the mtDNA copy number (mtDNA depletion syndrome). In our cohort the onset of disease was later than the classic forms of LS described in the literature with six of eight patients presenting as late-onset or adult-onset LS, with more complex neurological phenotype and systemic involvement and more good survival than previously reported (Sofou et al., 2014; Lee et al., 2009; Huntsman et al., 2005; Zhang et al., 2007). Most of the patients presenting with ataxia and movement disorders (dystonia, ataxia, chorea or parkinsonism) are the symptoms of LS and peripheral neuropathy was present in all patients as associated symptom common in mitochondrial disorders reinforcing the importance of electroneuromyography studies in the evaluation of patients with suspected mitochondrial disease.

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