Infantile neuroaxonal dystrophy: What's most important for the diagnosis?

Carrilho, Inês; Santos, Mariline; Guimarães, António; Teixeira, João; Chorão, Rui; Martins, Márcia; Dias, Cristina; Gregory, Allison; Westaway, Shawn K.; Nguyen, Thi My Linh; Hayflick, Susan J.; Barbot, Clara

doi:10.1016/j.ejpn.2008.01.005

Cited by 47 publications

(53 citation statements)

References 26 publications

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“…The accompanying clinical INAD symptoms were found to recapitulate in subsequently generated global iPLA 2 ␤ -null mice ( 330,331 ). Screening of DNA from human patients with INAD and NBIA identifi ed 80% of INAD and 20% of NBIA patients with mutations in the PLA2G6 gene, and neuropathologic changes that were analogous to those associated with Parkinson's and Alzheimer's diseases ( 332,333 ). Studies using iPLA 2 ␤ -null mice suggest degeneration of mitochondrial inner membranes and presynaptic membranes ( 334 ), reductions in capacitative Ca 2+ entry in astrocytes ( 335 ), point mutation in the Ank repeat producing an inactive iPLA 2 ␤ protein ( 336 ), and neuro-infl ammation and Purkinje cell loss ( 337 ) as potential underlying mechanisms that lead to pathogenesis in neurodegenerative disorders associated with brain iron accumulations such as INAD, NBIA ( 338 ), Karak syndrome ( 339 ), and Parkinson's and Alzheimer's diseases accompanied by iron accumulations.…”

Section: Ipla 2 ␤ and Diseasesmentioning

confidence: 99%

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Ramanadham

Ali

Ashley

et al. 2015

Journal of Lipid Research

160

170

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The Ca 2+ -independent phospholipases A 2 (iPLA 2 s) are part of a diverse family of PLA 2 s that hydrolyze the sn -2 substituent from membrane phospholipids to release a free fatty acid and a lysolipid ( 1, 2 ). These enzymes are ubiquitously expressed, and in contrast to secretory PLA 2 s (sPLA 2 s) and cytosolic PLA 2 s (cPLA 2 s), do not require Ca 2+ for either translocation or activity. Some of the fi rst descriptions of iPLA 2 activity were in the mid-to late-1980s with the identifi cation of a plasmalogen-selective PLA 2 in Abstract Among the family of phospholipases A 2 (PLA 2 s) are the Ca 2+ -independent PLA 2 s (iPLA 2 s) and they are designated group VI iPLA 2 s. In relation to secretory and cytosolic PLA 2 s, the iPLA 2 s are more recently described and details of their expression and roles in biological functions are rapidly emerging. The iPLA 2 s or patatin-like phospholipases (PNPLAs) are intracellular enzymes that do not require Ca 2+ for activity, and contain lipase (GXSXG) and nucleotide-binding (GXGXXG) consensus sequences. Though nine PNPLAs have been recognized, PNPLA8 (membraneassociated iPLA 2 ␥ ) and PNPLA9 (cytosol-associated iPLA 2 ␤ ) are the most widely studied and understood. The iPLA 2 s manifest a variety of activities in addition to phospholipase, are ubiquitously expressed, and participate in a multitude of biological processes, including fat catabolism, cell differentiation, maintenance of mitochondrial integrity, phospholipid remodeling, cell proliferation, signal transduction, and cell death. As might be expected, increased or decreased expression of iPLA 2 s can have profound effects on the metabolic state, CNS function, cardiovascular performance, and cell survival; therefore, dysregulation of iPLA 2 s can be a critical factor in the development of many diseases. This review is aimed at providing a general framework of the current understanding of the iPLA 2 s and discussion of the potential mechanisms of action of the iPLA 2 s and related involved lipid mediators. -Ramanadham, S

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Section: Ipla 2 ␤ and Diseasesmentioning

confidence: 99%

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Ramanadham

Ali

Ashley

et al. 2015

Journal of Lipid Research

160

170

View full text Add to dashboard Cite

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“…However, the absence of signal hyperintensity in the cerebellar cortex does not rule out the diagnosis of infantile neuroaxonal dystrophy. 7 Interestingly, the p.Leu481Gln mutation found in our patient was previously reported always in homozygosis in 2 infantile neuroaxonal dystrophy-affected individuals from separate families, 8 but no neonatal onset was described. In this cohort of patients, the average age of symptom onset was 1.1 years, presenting psychomotor regression characterized by early hypotonia progressing to tetraparesis as described in the classical form of infantile neuroaxonal dystrophy.…”

Section: Discussionmentioning

confidence: 78%

A Case of Infantile Neuroaxonal Dystrophy of Neonatal Onset

et al. 2014

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Infantile neuroaxonal dystrophy is a rare neurodegenerative disorder, with onset in the first or second year of life. Mutations in the PLA2G6 gene encoding iPLA2-VI, a calcium-independent phospholipase, have been identified in these children. In classic infantile neuroaxonal dystrophy-affected children, psychomotor regression is the most frequent presentation, usually with ataxia and optic atrophy, followed by the development of tetraparesis. We report a child carrying a homozygous mutation in the PLA2G6 gene with neonatal onset of disease and somewhat different clinical phenotype such as severe congenital hypotonia, marked weakness, and bulbar signs suggesting that infantile neuroaxonal dystrophy can start at birth with atypical phenotype.

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“…This indicates that the absence of cerebellar cortex signal hyperintensity does not rule out an INAD diagnosis (13). (2,6,(12)(13)(14)(15)(16)(17). In China, only 2 studies reported PLA2G6-associated neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%