Pelizaeus-Merzbacher disease

ペリツェウス・メルツバッヘル病

WordNet

1. an impairment of health or a condition of abnormal functioning
2. caused by or altered by or manifesting disease or pathology; "diseased tonsils"; "a morbid growth"; "pathologic tissue"; "pathological bodily processes" (同)morbid, pathologic, pathological

PrepTutorEJDIC

1. (体の)『病気』,疾患 / (精神・道徳などの)病気,病弊
2. 女性の話術芸人 =diseur
3. 病気にかかった / 病的な,不健全な(morbid)

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/06/04 11:55:12」(JST)

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Pelizaeus–Merzbacher disease
Classification and external resources
ICD-10	E75.2
ICD-9	330.0
OMIM	312080
DiseasesDB	29467
eMedicine	neuro/520
MeSH	D020371

Pelizaeus–Merzbacher disease (PMD) is a rare central nervous system disorder in which coordination, motor abilities, and intellectual function are delayed to variable extents.

Classification

The disease is one in a group of genetic disorders collectively known as leukodystrophies that affect growth of the myelin sheath, the fatty covering—which acts as an insulator—on nerve fibers in the CNS. PMD is generally caused by a recessive mutation of the gene on the long arm of the X-chromosome (Xq21-22) that codes for a myelin protein called proteolipid protein 1 or PLP1. The majority of disease-causing mutations result in duplications of the entire PLP1 gene. There are several forms of Pelizaeus-Merzbacher disease including, classic, connatal, transitional, and adult variants. Interestingly, deletions at the PLP1 locus (which are rarer) cause a milder form of PMD than is observed with the typical duplication mutations, which demonstrates the critical importance of gene dosage at this locus for normal CNS function. Some of the remaining cases of PMD are accounted for by mutations in the gap junction A12 (GJA12) gene, and are now called Pelizaeus-Merzbacher-like disease (PMLD). Other cases of apparent PMD do not have mutations in either the PLP1 or GJA12 genes, and are presumed to be caused either by mutations in other genes, or by mutations not detected by sequencing the PLP1 gene exons and neighboring intronic regions of the gene. Among these is a new genetic disorder (discovered in 2003, 2004) which is caused by mutation in the transporter of thyroid hormone, MCT8, also known as SLC16A2, is believed to be account for a significant fraction of the undiagnosed neurological disorders (usually resulting in hypotonic/floppy infants with delayed milestones). This genetic defect was known as Allan-Herndon-Dudley syndrome (since 1944) without knowing its actual cause. Some of the signs for this disorder are as follows: normal to slightly elevated TSH, elevated T₃ and reduced T₄ (ratio of T₃/T₄ is about double its normal value). Normal looking at birth and for the first few years, hypotonic (floppy), in particular difficulty to hold the head, possibly difficulty to thrive, possibly with delayed myelination (if so, some cases are reported with an MRI pattern similar to Pelizaeus–Merzbacher disease, known as PMD,) possibly with decreased mitochondrial enzyme activities, possibly with fluctuating lactate level. Patients have an alert face, a limited IQ, patients may never talk/walk, 50% need feeding tube, patients have a normal life span. MCT8 can be ruled out with a simple TSH/T₄/T₃ thyroid test.

Milder mutations of the PLP1 gene that mainly cause leg weakness and spasticity, with little or no cerebral involvement, are classified as spastic paraplegia 2 (SPG2). The onset of Pelizaeus–Merzbacher disease is usually in early infancy. The most characteristic early signs are nystagmus (rapid, involuntary, rhythmic motion of the eyes) and hypotonia (low muscle tone). Motor abilities are delayed or never acquired, mostly depending upon the severity of the mutation. Most children with PMD learn to understand language, and usually have some speech. Other signs may include tremor, lack of coordination, involuntary movements, weakness, unsteady gait, and over time, spasticity in legs and arms. Muscle contractures (shrinkage or shortening of a muscle) often occur over time. Mental functions may deteriorate. Some patients may have convulsions and skeletal deformation, such as scoliosis, resulting from abnormal muscular stress on bones.

Diagnosis

The diagnosis of PMD is often first suggested after identification by magnetic resonance imaging (MRI) of abnormal white matter (high T2 signal intensity, i.e. T2 lengthening) throughout the brain, which is typically evident by about 1 year of age, but more subtle abnormalities should be evident during infancy. Unless there is a family history consistent with sex-linked inheritance, the condition is often misdiagnosed as cerebral palsy. Once a PLP1 or GJA12 mutation is identified, prenatal diagnosis or preimplantation genetic diagnostic testing is possible. .

Treatment

There is no cure for PMD, nor is there a standard course of treatment. Treatment, which is symptomatic and supportive, may include medication for seizures and spasticity. Regular evaluations by physical medicine and rehabilitation, orthopedic, developmental and neurologic specialists should be made to ensure optimal therapy and educational resources. The prognosis for those with Pelizaeus–Merzbacher disease is highly variable, with children with the most severe form (so-called connatal) usually not surviving to adolescence, but survival into the sixth or even seventh decades is possible, especially with attentive care. Genetic counseling should be provided to the family of a child with PMD.

In December 2008, StemCells Inc., a biotech company in Palo Alto, received clearance from the U.S. Food and Drug Administration (FDA) to conduct Phase I clinical trials in PMD to assess the safety of transplanting human neural stem cells as a potential treatment for PMD. The trial was initiated in November 2009 at the University of California, San Francisco (UCSF) Children's Hospital.

See also

• The Myelin Project
• The Stennis Foundation

References

External links

• Pelizaeus-Merzbacher.org - Videos and information about the disorder's symptom, diagnosis, prognosis, research & potential treatment
• The Stennis Foundation - Registered charity committed to raising awareness and funds for Leukodystrophies research
• The Stennis Foundation's MySpace site
• Pelizaeus-Merzbacher Disease. NINDS/National Health Institutes.
• pmd at NIH/UW GeneTests
• Uhlenberg B, Schuelke M, Rüschendorf F, Ruf N, Kaindl A, Henneke M, Thiele H, Stoltenburg-Didinger G, Aksu F, Topaloğlu H, Nürnberg P, Hübner C, Weschke B, Gärtner J (2004). "Mutations in the gene encoding gap junction protein alpha 12 (connexin 46.6) cause Pelizaeus-Merzbacher-like disease". Am J Hum Genet 75 (2): 251–60. doi:10.1086/422763. PMC 1216059. PMID 15192806. 
• PMD foundation web site. PMD Foundation (US)
• PMD Clinical Trial - UCSF Neonatology Clinical Trial for PMD

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. ペリツェウス・メルツバッハー病 pelizaeus merzbacher disease
• 2. 消失性白質疾患（Vanishing white matter disease） vanishing white matter disease
• 3. 脊髄に影響を与える疾患 disorders affecting the spinal cord
• 4. 異染性白質ジストロフィー metachromatic leukodystrophy
• 5. 急性運動失調を呈する小児に対するアプローチ approach to the child with acute ataxia

English Journal

• Characterization of a PLP-overexpressing transgenic rat, a model for the connatal form of Pelizaeus-Merzbacher disease.

• Mayer JA, Larsen EC, Kondo Y, Duncan ID.AbstractPelizaeus-Merzbacher disease (PMD) most frequently results from duplication of the Plp1 gene with a correlation between disease severity and increasing copy number of the gene. Animal models of PMD, in particular those overexpressing the Plp1 gene, have been sought in attempts to provide systems in which potential therapies can be tested. Here we describe a rat model of the severe connatal form of PMD and provide a detailed characterization of its pathology and molecular biology, prior to testing therapeutic approaches. We determined the exact copy number of Plp1, and the resulting effects on RNA and protein expression. Distinct differences in myelin and disparate distributions of myelin protein markers in comparison to wild-type controls were observed. Altered expression of Plp1 also caused an increase in the apoptotic cell death of oligodendrocytes. These results provide the platform from which to test the effectiveness of in vivo therapies.
• Neurobiology of disease.Neurobiol Dis.2011 Jul 18. [Epub ahead of print]
• Pelizaeus-Merzbacher disease (PMD) most frequently results from duplication of the Plp1 gene with a correlation between disease severity and increasing copy number of the gene. Animal models of PMD, in particular those overexpressing the Plp1 gene, have been sought in attempts to provide systems in
• PMID 21784154

Japanese Journal

• GJA12遺伝子変異をみとめず, 新規の白質ジストロフィーがうたがわれた1例

• 石川 知子,佐藤 紀美子,島崎 里恵,後藤 勝政,松田 貴雄,石浦 浩之
• 臨床神経学 50(1), 7-11, 2010-01-01
• NAID 10026291291

Related Links

• Pelizaeus?Merzbacher disease - Wikipedia, the free encyclopedia

Pelizaeus?Merzbacher disease (PMD) is a rare central nervous system disorder in which coordination, motor abilities, and intellectual function are delayed to variable extents. Contents. 1 Classification; 2 Diagnosis; 3 Treatment ...

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★リンクテーブル★

リンク元	「ペリツェウス・メルツバッヘル病」
関連記事	「disease」

「ペリツェウス・メルツバッヘル病」

　　[★]

英

Pelizaeus-Merzbacher disease

同

ペリツェウス・メルツバッハー病、Pelizaeus-Merzbacher病

[show details]

ペリツェウス・メルツバッヘル病 : 75 件
ペリツェウス・メルツバッハー病 : 58 件

• アメリカの場合、数十万人に一人という、きわめてまれな進行性家族性の中枢神経疾患。(参考2)
• 幼少期に発症し、精神・言語・運動等の障害がおこる。(参考2)
• 大部分の症例はX染色体上に存在するPLP1遺伝子の重複ないし点突然変異が原因で発生し、X連鎖劣性遺伝形式で遺伝するとされている。(参考2)

参考

• 1. OMIM

http://www.ncbi.nlm.nih.gov/omim/312080

• 2.

http://www.sophialaw.jp/law-web/sophia_law_review_files/contents/4803_04/4803_04makino_notes.htm

「disease」

　　[★]

• n.

疾患：illnessより厳密な概念。「ある臓器に明確な障害が確認され、それによって症状が出ているとはっきり説明できる場合」 (PSY.9)

特定の原因、病態生理、症状、経過、予後、病理組織所見が全てそろった場合 (PSY.9)

• something that is very wrong with people's attitudes, way of life or with society.

関

ail、ailment、disease entity、disorder、ill、illness、malady、sick、sickness

• 注意

disease ≠ illness ≠ disorder