Progressive cerebral vascular degeneration with mitochondrial encephalopathy

Title

Progressive cerebral vascular degeneration with mitochondrial encephalopathy

Creator

Longo N; Schrijver I; Vogel H; Pique LM; Cowan TM; Pasquali M; Steinberg GK; Hedlund GL; Ernst SL; Gallagher RC; Enns GM

Publisher

American Journal Of Medical Genetics.Part A

Date

2008

Subject

Child; Female; Humans; Cerebrovascular Circulation; Q3 Literature Search; Acyl-CoA Dehydrogenase/deficiency/genetics; Brain/blood supply/physiopathology; Leu/genetics; Magnetic Resonance Angiography; MELAS Syndrome/ge [Genetics]; Point Mutation; RNA; Transfer

Description

MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) is a maternally inherited disorder characterized by recurrent cerebral infarctions that do not conform to discreet vascular territories. Here we report on a patient who presented at 7 years of age with loss of consciousness and severe metabolic acidosis following vomiting and dehydration. She developed progressive sensorineural hearing loss, myopathy, ptosis, short stature, and mild developmental delays after normal early development. Biochemical testing identified metabolites characteristic of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (hexanoylglycine and suberylglycine), but also severe lactic acidemia (10-25 mM) and, in urine, excess of lactic acid, intermediates of the citric cycle, and marked ketonuria, suggesting mitochondrial dysfunction. She progressed rapidly to develop temporary cortical blindness. Brain imaging indicated generalized atrophy, more marked on the left side, in addition to white matter alterations consistent with a mitochondrial disorder. Magnetic resonance angiography indicated occlusion of the left cerebral artery with development of collateral circulation (Moyamoya syndrome). This process worsened over time to involve the other side of the brain. A muscle biopsy indicated the presence of numerous ragged red fibers. Molecular testing confirmed compound heterozygosity for the common mutation in the MCAD gene (985A>G) and a second pathogenic mutation (233T>C). MtDNA testing indicated that the muscle was almost homoplasmic for the 3243A>T mutation in tRNALeu, with a lower mutant load (about 50% heteroplasmy) in blood and skin fibroblasts. These results indicate that mitochondrial disorders may be associated with severe vascular disease resulting in Moyamoya syndrome. The contribution of the concomitant MCAD deficiency to the development of the phenotype in this case is unclear.
2008

Rights

Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).

Type

Journal Article

Citation List Month

Backlog

Pages

361-367

Issue

3

Volume

146

Citation

Longo N; Schrijver I; Vogel H; Pique LM; Cowan TM; Pasquali M; Steinberg GK; Hedlund GL; Ernst SL; Gallagher RC; Enns GM, “Progressive cerebral vascular degeneration with mitochondrial encephalopathy,” Pediatric Palliative Care Library, accessed December 3, 2021, https://pedpalascnetlibrary.omeka.net/items/show/14462.

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