Danon disease

Danon disease
Classification and external resources
Specialty	endocrinology
ICD-10	E74.0
OMIM	300257
MeSH	D052120

Danon disease (or glycogen storage disease Type IIb) is a metabolic disorder.

Danon disease is associated with heart muscle abnormalities resembling severe hypertrophic cardiomyopathy.^[1]

Genetics

It is associated with LAMP2.^[2] The status of this condition as a GSD has been disputed.^[3]

History

It was characterized by Moris Danon in 1981.^[4]

The first description of Danon Disease was in 1981 when 2 boys with heart and skeletal muscle disease (muscle weakness) and mental retardation were described. The disease is named after Dr. Danon who first wrote about the disease.

The first case reported in the Middle East was a family diagnosed with Danon Disease in the eastern region of United Arab Emirates with a new LAMP2 mutation; discovered by the Egyptian cardiologist Dr. Mahmoud Ramadan the associate professor of Cardiology in Mansoura University (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 (http://www.albayan.ae/across-the-uae/news-and-reports/2016-02-20-1.2577082) making this family the largest one with patients and carriers of Danon disease.

Danon Disease looked initially like another rare genetic condition called 'Pompe' disease. Under the microscope, muscles from the Danon Disease patients looked similar to muscles from Pompe disease patients. However the tests for Pompe disease are normal in Danon Disease patients. This shows that Danon Disease is caused by something different than Pompe disease.

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 mental retardation can be present
The muscle weakness can be severe and can affect endurance and even the ability to walk
The 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,^[5] leading to death unless heart transplant is performed.
Problems with the electrical conduction in the heart can occur. Sometimes the conduction problem is called Wolff-Parkinson-White syndrome.
The symptoms are usually progressive and the boys tend to gradually get worse
Some boys may have problems with their vision or a problem with the pigment in their retinas (in the back of their eyes)
Danon Disease is rare and unfamiliar to most physicians. It can be mistaken for other forms of heart disease and/or muscular dystrophies.

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 mental retardation are usually ABSENT
Muscle weakness is often absent or subtle. Some females will tire easily with exercise
Heart muscle disease (cardiomyopathy) is often absent in girls: some women will develop this in adulthood. Cardiomyopathy can be associated with atrial fibrillation and embolic strokes.
Problems with the electrical conduction in the heart can occur. Sometimes the conduction problem is called 'Wolff-Parkinson-White' syndrome
Symptoms in females progress more slowly than in males. Heart disease may not be a problem for females until adulthood
Some females will have problems with their vision or a problem with the pigment in the back of their retinas (in the back of their eyes)
Danon Disease is rare and unfamiliar to most physicians. The milder and more subtle symptoms in females probably make it harder to diagnose females who have Danon Disease

Causes of Danon Disease

The cause of Danon Disease is known, but not well-understood. The genetic defect involves a gene called LAMP2. In persons with Danon Disease the LAMP2 gene is damaged (or 'mutated') and normal LAMP2 protein is no longer made. While we do not fully understand what the function of the LAMP2 gene is, we do know that LAMP2 protein is located in small structures in our cells called lysosomes.

References

↑ Maron BJ, Roberts WC, Arad M, et al. (March 2009). "Clinical Outcome and Phenotypic Expression in LAMP2 Cardiomyopathy". JAMA 301 (12): 1253–1259. doi:10.1001/jama.2009.371. PMID 19318653.
↑ Lobrinus JA, Schorderet DF, Payot M, et al. (April 2005). "Morphological, clinical and genetic aspects in a family with a novel LAMP-2 gene mutation (Danon disease)". Neuromuscular disorders : NMD 15 (4): 293–8. doi:10.1016/j.nmd.2004.12.007. PMID 15792868.
↑ Nishino I, Fu J, Tanji K, et al. (August 2000). "Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease)". Nature 406 (6798): 906–10. doi:10.1038/35022604. PMID 10972294.
↑ Danon MJ, Oh SJ, DiMauro S, et al. (January 1981). "Lysosomal glycogen storage disease with normal acid maltase". Neurology 31 (1): 51–7. doi:10.1212/wnl.31.1.51. PMID 6450334.
↑ Spinazzi M, Fanin M, Melacini P, Nascimbeni AC, Angelini C. Cardioembolic stroke in Danon disease. Clin Genet. 2008;73:388-90.

http://danondisease.org

Sex linkage: X-linked disorders

X-linked recessive

Immune	Chronic granulomatous disease (CYBB) Wiskott–Aldrich syndrome X-linked severe combined immunodeficiency X-linked agammaglobulinemia Hyper-IgM syndrome type 1 IPEX X-linked lymphoproliferative disease Properdin deficiency

Hematologic	Haemophilia A Haemophilia B X-linked sideroblastic anemia

Endocrine	Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy KAL1 Kallmann syndrome X-linked adrenal hypoplasia congenita

Metabolic	Amino acid: Ornithine transcarbamylase deficiency Oculocerebrorenal syndrome Dyslipidemia: Adrenoleukodystrophy Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency Pyruvate dehydrogenase deficiency Danon disease/glycogen storage disease Type IIb Lipid storage disorder: Fabry's disease Mucopolysaccharidosis: Hunter syndrome Purine-pyrimidine metabolism: Lesch–Nyhan syndrome Mineral: Menkes disease/Occipital horn syndrome

Nervous system	X-linked mental retardation: Coffin–Lowry syndrome MASA syndrome X-linked alpha thalassemia mental retardation syndrome Siderius X-linked mental retardation syndrome Eye disorders: Color blindness (red and green, but not blue) Ocular albinism (1) Norrie disease Choroideremia Other: Charcot–Marie–Tooth disease (CMTX2-3) Pelizaeus–Merzbacher disease SMAX2

Skin and related tissue	Dyskeratosis congenita Hypohidrotic ectodermal dysplasia (EDA) X-linked ichthyosis X-linked endothelial corneal dystrophy

Neuromuscular	Becker's muscular dystrophy/Duchenne Centronuclear myopathy (MTM1) Conradi–Hünermann syndrome Emery–Dreifuss muscular dystrophy 1

Urologic	Alport syndrome Dent's disease X-linked nephrogenic diabetes insipidus

Bone/tooth	AMELX Amelogenesis imperfecta

No primary system	Barth syndrome McLeod syndrome Smith–Fineman–Myers syndrome Simpson–Golabi–Behmel syndrome Mohr–Tranebjærg syndrome Nasodigitoacoustic syndrome

X-linked dominant

X-linked hypophosphatemia Focal dermal hypoplasia Fragile X syndrome Aicardi syndrome Incontinentia pigmenti Rett syndrome CHILD syndrome Lujan–Fryns syndrome Orofaciodigital syndrome 1 Craniofrontonasal dysplasia

Genetic disorder, organelle: Peroxisomal disorders and lysosomal structural disorders (E80.3, 277.86)

Peroxisome biogenesis disorder	Zellweger syndrome Neonatal adrenoleukodystrophy Infantile Refsum disease Adult Refsum disease-2 RCP 1

Enzyme-related	Acatalasia RCP 2&3 Mevalonate kinase deficiency D-bifunctional protein deficiency Adult Refsum disease-1

Transporter-related	X-linked adrenoleukodystrophy

Lysosomal	Danon disease

See also: proteins, intermediates

This article is issued from Wikipedia - version of the Tuesday, March 08, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.