Subacute Necrotizing Encephalomyelopathy in an Infant

Leigh, Denis

doi:10.1136/jnnp.14.3.216

Cited by 727 publications

(405 citation statements)

References 6 publications

(5 reference statements)

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“…Since its initial description (Leigh 1951), LS has evolved from a distinct neuropathological disorder defined by postmortem histopathological findings to a clinical entity characterized by progressive neurodegenerative disease with symptoms and signs of brainstem and/or basal ganglia disease, raised lactate levels in blood and/or cerebrospinal fluid (CSF), and typical neuroimaging and/or neuropathological abnormalities (Rahman et al 1996). More recently, Baertling et al (2014) refined the diagnostic criteria to include the three most commonly described features: (1) neurodegenerative disease with variable symptoms; (2) bilateral neuroimaging or CNS lesions and (3) a variety of nuclear or mitochondrially encoded genetic causes of deficient mitochondrial energy metabolism.…”

Section: Introductionmentioning

confidence: 99%

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

et al. 2016

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Leigh syndrome (LS), or subacute necrotizing encephalomyelopathy, is a genetically heterogeneous, relentlessly progressive, devastating neurodegenerative disorder that usually presents in infancy or early childhood. A diagnosis of Leigh-like syndrome may be considered in individuals who do not fulfil the stringent diagnostic criteria but have features resembling Leigh syndrome.We describe a unique presentation of Leigh-like syndrome in a 3-year-old boy with elevated 3-hydroxyisovalerylcarnitine (C5-OH) on newborn screening (NBS).Subsequent persistent plasma elevations of C5-OH and propionylcarnitine (C3) as well as fluctuating urinary markers were suggestive of multiple carboxylase deficiency (MCD). Normal enzymology and mutational analysis of genes encoding holocarboxylase synthetase (HLCS) and biotinidase (BTD) excluded MCD. Biotin uptake studies were normal excluding biotin transporter deficiency. His clinical features at 13 months of age comprised psychomotor delay, central hypotonia, myopathy, failure to thrive, hypocitrullinemia, recurrent episodes of decompensation with metabolic keto-lactic acidosis and an episode of hyperammonemia. Biotin treatment from 13 months of age was associated with increased patient activity, alertness,

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Section: Introductionmentioning

confidence: 99%

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

et al. 2016

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“…cDNA and protein mutations and annotations regarding animal models are also useful potential supplements to the Leigh Map. Leigh syndrome is a defined disorder5 wherein certain phenotypes appear almost ubiquitously, including hypotonia (91% of patients), developmental delay (82%), lactic acidosis (78%), and failure to thrive (61%). The failure to deduce the correct candidate genes for a minority of our test cases was due to the predominant presence of these common Leigh syndrome phenotypes and a lack of discriminating phenotypes.…”

Section: Future Prospectsmentioning

confidence: 99%

“…Leigh syndrome is a progressive neurodegenerative disorder defined neuropathologically by spongiform basal ganglia and brainstem lesions 4, 5. Clinical manifestations include psychomotor retardation, with regression, and progressive neurological abnormalities related to basal ganglia and/or brainstem dysfunction, often resulting in death within 2 years of initial presentation 4, 6.…”

mentioning

confidence: 99%

Leigh map: A novel computational diagnostic resource for mitochondrial disease

Rahman¹,

Noronha

Thiele

et al. 2017

Annals of Neurology

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“…Leigh Syndrome (Bilateral Symmetric Basal Ganglia Lesions) Denis Leigh, a British neuropathologist, first described this syndrome in 1951, in a 7-month-old patient with "subacute necrotizing encephalomyelopathy" [90]. Neuroimaging shows calcifications on computed tomography or MRI with bilateral and symmetric lesions of the basal ganglia, periaqueductal grey, pons, midbrain, brainstem, cerebellum, and, rarely, white matter [91,92].…”

Section: Stroke-like Lesions In Nonvascular Distributionmentioning

confidence: 99%

Mitochondrial Disease in Childhood: Nuclear Encoded

2013

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Primary mitochondrial disorders are clinically and genetically heterogeneous, caused by an alteration(s) in either mitochondrial DNA or nuclear DNA, and affect the respiratory chain's ability to undergo oxidative phosphorylation, leading to decreased production of adenosine triphosphophate and subsequent energy failure. These disorders may present at any age, but children tend to have an acute onset of disease compared with subacute or slowly progressive presentation in adults. Varying organ involvement also contributes to the phenotypic spectrum seen in these disorders. The childhood presentation of primary mitochondrial disease is mainly due to nuclear DNA mutations, with mitochondrial DNA mutations being less frequent in childhood and more prominent in adulthood disease. The clinician should be aware of the pediatric presentation of mitochondrial disease and have an understanding of the myriad of nuclear genes responsible for these disorders. The nuclear genes can be best understood by utilizing a classification system of location and function within the mitochondria.

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Subacute Necrotizing Encephalomyelopathy in an Infant

Cited by 727 publications

References 6 publications

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

Leigh-Like Syndrome Due to Homoplasmic m.8993T>G Variant with Hypocitrullinemia and Unusual Biochemical Features Suggestive of Multiple Carboxylase Deficiency (MCD)

Leigh map: A novel computational diagnostic resource for mitochondrial disease

Mitochondrial Disease in Childhood: Nuclear Encoded

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