“Danon disease”的意思、由来-开放百科全书

Symptoms

Males

In males the symptoms of Danon Disease are more severe. Features of Danon Disease in males are:

An early age of onset of muscle weakness and heart disease (onset in childhood or adolescence)

Some learning problems or intellectual disability can be present

Muscle weakness can be severe and can affect endurance and the ability to walk

Heart disease (cardiomyopathy) can be severe and can lead to a need for medications. It usually progress to heart failure, commonly complicated by atrial fibrillation and embolic strokes with severe neurological disability,^[3] leading to death unless heart transplant is performed.

Cardiac conduction abnormalities can occur. Wolff-Parkinson-White syndrome is a common conduction pattern in Danon disease.

Symptoms are usually gradually progressive

Some individuals may have visual disturbances, and/or retinal pigment abnormalities

Danon Disease is rare and unfamiliar to most physicians. It can be mistaken for other forms of heart disease and/or muscular dystrophies, including Pompe disease.

Females

In females the symptoms of Danon Disease are less severe. Common symptoms of Danon Disease in females are:

A later age of onset of symptoms. Many females will not have obvious symptoms until late adolescence or even adulthood.

Learning problems and intellectual disability are usually ABSENT

Muscle weakness is often absent or subtle. Some females will tire easily with exercise

Cardiomyopathy) is often absent in childhood. Some women will develop this in adulthood. Cardiomyopathy can be associated with atrial fibrillation and embolic strokes.

Cardiac conduction abnormalities can occur. Wolff-Parkinson-White syndrome is a common conduction pattern in Danon disease.

Symptoms in females progress more slowly than in males.

Some females may have visual disturbances, and/or retinal pigment abnormalities

Danon Disease is rare and unfamiliar to most physicians. The milder and more subtle symptoms in females can make it more difficult to diagnose females with Danon Disease

Causes

Although the genetic cause of Danon Disease is known, the mechanism of disease is not well understood. Danon disease involves a genetic defect (mutation) in a gene called LAMP2, which results in a change to the normal protein structure. While the function of the LAMP2 gene is not well understood, it is known that LAMP2 protein is primarily located in small structures within cells called lysosomes.

Genetics

It is associated with LAMP2.^[4] The status of this condition as a GSD has been disputed.^[5]

Diagnosis

Treatment

RP-A501 is an AAV-based gene therapy aimed to restore the LAMP-2 gene which is defective in patients afflicted with Danon Disease.

History

Danon disease was characterized by Moris Danon in 1981.^[6] Dr. Danon first described the disease in 2 boys with heart and skeletal muscle disease (muscle weakness), and intellectual disability.

The first case of Danon disease reported in the Middle East was a family diagnosed in the eastern region of United Arab Emirates with a new LAMP2 mutation; discovered by the Egyptian cardiologist Dr. Mahmoud Ramadan^[7] the associate professor of Cardiology in Mansoura University^[8] (Egypt) after doing genetic analysis for all the family members in Bergamo, Italy where 6 males were diagnosed as Danon disease patients and 5 female were diagnosed as carriers; as published in Al-Bayan newspaper in 20 February 2016^[9] making this family the largest one with patients and carriers of Danon disease.

Danon Disease has overlapping symptoms with another rare genetic condition called 'Pompe' disease. Microscopically, muscles from Danon Disease patients appear similar to muscles from Pompe disease patients. However, intellectual disability is rarely, if ever, a symptom of Pompe disease. Negative enzymatic or molecular genetic testing for Pompe disease can help rule out this disorder as a differential diagnosis.

References

1. ^{{Cite web|url=https://omim.org/entry/300257|title=OMIM Entry - # 300257 - DANON DISEASE|website=omim.org|language=en-us|access-date=2017-07-11}}
2. ^{{cite journal |vauthors=Maron BJ, Roberts WC, Arad M, etal |title=Clinical Outcome and Phenotypic Expression in LAMP2 Cardiomyopathy |journal=JAMA |volume=301 |issue=12 |pages=1253–1259 |date=March 2009 |pmid= 19318653|doi= 10.1001/jama.2009.371|url=http://jama.ama-assn.org/cgi/content/abstract/301/12/1253|pmc=4106257}}
3. ^Spinazzi M, Fanin M, Melacini P, Nascimbeni AC, Angelini C. Cardioembolic stroke in Danon disease. Clin Genet. 2008;73:388-90.
4. ^{{cite journal |vauthors=Lobrinus JA, Schorderet DF, Payot M, etal |title=Morphological, clinical and genetic aspects in a family with a novel LAMP-2 gene mutation (Danon disease) |journal=Neuromuscular Disorders |volume=15 |issue=4 |pages=293–8 |date=April 2005 |pmid=15792868 |doi=10.1016/j.nmd.2004.12.007 |url=http://linkinghub.elsevier.com/retrieve/pii/S0960-8966(05)00019-2}}
5. ^{{cite journal |vauthors=Nishino I, Fu J, Tanji K, etal |title=Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease) |journal=Nature |volume=406 |issue=6798 |pages=906–10 |date=August 2000 |pmid=10972294 |doi=10.1038/35022604}}
6. ^{{cite journal |vauthors=Danon MJ, Oh SJ, DiMauro S, etal |title=Lysosomal glycogen storage disease with normal acid maltase |journal=Neurology |volume=31 |issue=1 |pages=51–7 |date=January 1981 |pmid=6450334 |doi= 10.1212/wnl.31.1.51|url=}}
7. ^{{cite web|url=https://www.researchgate.net/profile/Mahmoud_Ramadan|title=Mahmoud Ramadan|work=ResearchGate}}
8. ^{{cite web|url=http://www.mans.edu.eg/en|title=Mansoura University, Egypt}}
9. ^{{cite web|url=http://www.albayan.ae/across-the-uae/news-and-reports/2016-02-20-1.2577082|title="دانون" مرض نادر يصيب القلب بالتضخم|author=الفجيرة - ابتسام الشاعر|work=البيان|date=2016-02-19}}