関: neuroaxonal dystrophy

WordNet

of or relating to infants or infancy; "infantile paralysis"
being or befitting or characteristic of an infant; "infantile games"
any degenerative disorder resulting from inadequate or faulty nutrition

PrepTutorEJDIC

《名詞の前にのみ用いて》幼時の / 子供じみた;子供らしい
栄養障害 / 筋萎縮症,筋ジストロフィー(筋肉の退化・萎縮・運動障害などが起こる病気)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/07/17 06:18:36」(JST)

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Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the nervous system. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Eventually they lose previously acquired skills.

Diagnosis

In some cases, signs and symptoms of infantile neuroaxonal dystrophy first appear later in childhood or during the teenage years and progress more slowly.

Children with infantile neuroaxonal dystrophy experience progressive difficulties with movement. Generally they have muscles that are at first weak and "floppy" (hypotonic), and then gradually become very stiff (spastic). Eventually, affected children lose the ability to move independently. Lack of muscle strength causes difficulty with feeding and breathing problems that can lead to frequent infections, such as pneumonia. Seizures occur in some affected children.

Rapid, involuntary eye movements (nystagmus), eyes that do not look in the same direction (strabismus), and vision loss due to deterioration (atrophy) of the optic nerve are characteristic of infantile neuroaxonal dystrophy. Hearing loss may also develop. Children with this disorder experience progressive deterioration of cognitive functions (dementia), and eventually lose awareness of their surroundings.

Infantile neuroaxonal dystrophy is characterized by the development of swellings called spheroid bodies in the axons, the fibers that extend from nerve cells (neurons) and transmit impulses to muscles and other neurons. A part of the brain called the cerebellum, which helps to control movements, may also be damaged. In some individuals with infantile neuroaxonal dystrophy, abnormal amounts of iron accumulate in a specific region of the brain called the basal ganglia.

Pathophysiology

Mutations in the PLA2G6 gene have been identified in most individuals with infantile neuroaxonal dystrophy. The PLA2G6 gene provides instructions for making an enzyme called an A2 phospholipase. This enzyme family is involved in metabolizing phospholipids. Phospholipid metabolism is important for many body processes, including helping to keep the cell membrane intact and functioning properly. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane.

Mutations in the PLA2G6 gene impair the function of the PLA2 group VI enzyme. This impairment of enzyme function may disrupt cell membrane maintenance and contribute to the development of spheroid bodies in the nerve axons. Although it is unknown how changes in this enzyme's function lead to the signs and symptoms of infantile neuroaxonal dystrophy, phospholipid metabolism problems have been seen in both this disorder and a related disorder called pantothenate kinase-associated neurodegeneration. These disorders, as well as the more common Alzheimer disease and Parkinson disease, also are associated with changes in brain iron metabolism. Researchers are studying the links between phospholipid defects, brain iron, and damage to nerve cells, but have not determined how the iron accumulation that occurs in some individuals with infantile neuroaxonal dystrophy may contribute to the features of this disorder.

A few individuals with infantile neuroaxonal dystrophy have not been found to have mutations in the PLA2G6 gene. The genetic cause of the condition in these cases is unknown; there is evidence that at least one other gene may be involved.

Mutations in the NAGA gene, resulting in alpha-N-acetylgalactosaminidase deficiency, cause an infantile neuroaxonal dystrophy known as Schindler disease.^[1]

Inheritance

Infantile neuroaxonal dystrophy has an autosomal recessive pattern of inheritance.

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene (PLA2G6) in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.

References

^ Wang AM, Schindler D, Desnick R (November 1990). "Schindler disease: the molecular lesion in the alpha-N-acetylgalactosaminidase gene that causes an infantile neuroaxonal dystrophy". J. Clin. Invest. 86 (5): 1752–6. doi:10.1172/JCI114901. PMC 296929. PMID 2243144.

External links

GeneReview/NIH/UW entry on Infantile Neuroaxonal Dystrophy
National Library of Medicine. Genetics Home Reference - Infantile neuroaxonal dystrophy

UpToDate Contents

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1. 全身疾患と関連した遺伝性ニューロパチー hereditary neuropathies associated with generalized disorders
2. 小児における運動減少性運動障害 bradykinetic movement disorders in children
3. 遺伝性ニューロパチーの概要 overview of hereditary neuropathies
4. 小児における運動過多な運動障害 hyperkinetic movement disorders in children
5. ジストニアの分類および評価 classification and evaluation of dystonia

English Journal

Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations.

Paisán-Ruiz C, Li A, Schneider SA, Holton JL, Johnson R, Kidd D, Chataway J, Bhatia KP, Lees AJ, Hardy J, Revesz T, Houlden H.SourceDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Neurobiology of aging.Neurobiol Aging.2012 Apr;33(4):814-23. Epub 2010 Jul 21.
The 2 major types of neurodegeneration with brain iron accumulation (NBIA) are the pantothenate kinase type 2 (PANK2)-associated neurodegeneration (PKAN) and NBIA2 or infantile neuroaxonal dystrophy (INAD) due to mutations in the phospholipase A2, group VI (PLA2G6) gene. We have recently demonstrate
PMID 20619503

Severe disturbance in the Ca2+ signaling in astrocytes from mouse models of human infantile neuroaxonal dystrophy (INAD) with mutated Pla2g6.

Strokin M, Seburn KL, Cox GA, Martens KA, Reiser G.SourceInstitut für Neurobiochemie, Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany.
Human molecular genetics.Hum Mol Genet.2012 Mar 22. [Epub ahead of print]
Infantile neuroaxonal dystrophy (INAD, OMIM #256600) is an inherited degenerative nervous system disorder characterized by nerve abnormalities in brain, spinal cord, and peripheral nerves. About 85% of INAD patients carry mutations in the PLA2G6 gene which encodes for a Ca(2+)-independent phospholip
PMID 22442204

Japanese Journal

Ca非依存性 phospholypase A2β ノックアウトマウスを用いた infantile neuroaxonal dystrophy の病態解析

隅寿恵,新沢康英,加藤信介,衛藤昌樹,辻本賀英,佐古田三郎
末梢神経 = Peripheral nerve 19(2), 407-409, 2008-12-01
NAID 10025625698

Spontaneous murine neuroaxonal dystrophy : a model of infantile neuroaxonal dystrophy

BOULEY D. M.
J. Comp. Pathol. 134, 161-170, 2006
NAID 30015229569

Related Pictures

★リンクテーブル★

リンク元	「乳児型神経軸索ジストロフィー」「neuroaxonal dystrophy」「INAD」
関連記事	「dystrophy」「infantile」「neuroaxonal dystrophy」

「乳児型神経軸索ジストロフィー」

Infantile neuroaxonal dystrophy
Classification and external resources
OMIM	256600
DiseasesDB	32201
MeSH	D019150
GeneReviews	PLA2G6-Associated Neurodegeneration;
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