Danon Disease

Clinical Characteristics
Ocular Features: 

The ocular features of Danon disease are less well known than the systemic manifestations and are as yet not fully delineated likely because not all patients have visual symptoms or fundus changes.  The most commonly described fundus abnormalities are pigmentary changes variously called a peripheral pigmentary retinopathy or a pigmentary atrophy in some cases.   Changes in pigmentation may be mild in both affected males and carrier females, but are generally more severe in males.  A bulls-eye maculopathy and color vision deficiencies have been described.  Loss of visual acuity is variable and may lead to symptoms before myopathy is evident.  Vision loss is usually progressive and may be reduced to hand motions.  OCT shows thinning of the photoreceptor and RPE layers.  The full field ERG is reduced in amplitude consistent with a generalized cone-rod dystrophy.

Systemic Features: 

This disorder, originally believed to be a type of glycogen storage disease, is actually a form of autophagic vacuolar myopathy.    The characteristic vacuoles are found in muscle cytoplasm surrounded by sarcolemmal proteins and basal lamina.  The primary extraocular disease occurs in the myocardium although skeletal muscle may also be involved.  Intellectual disability is a variable and inconsistent feature.  

Cardiac rhythm abnormalities are common and include AV nodal block, atrial fibrillation, and Wolff-Parkinson-White EKG findings.  Hypertrophic cardiomyopathy (and sometimes dilated cardiomyopathy) with primary involvement of the left ventricle is common.  Symptoms typically occur in males before the age of 20 years and somewhat later in females.

Some patients have muscular weakness and exercise intolerance.  Diagnosis can be made when the characteristic vacuoles are present in a muscle biopsy but their absence does not rule out the diagnosis.

Genetics

This is an X-linked dominant disorder caused by mutations in LAMP2 (Xp24).  Females are generally less severely affected than males. Most men with Danon disease have some intellectual disability as well as skeletal myopathy but these features are found in less than half of affected women.  

Treatment
Treatment Options: 

No known treatment is available for the ocular disease.  Transplantation can be an effective treatment for the cardiomyopathy which can be lethal even in adolescents.

References
Article Title: 

Cardiac arrhythmias in patients with Danon disease

Konrad T, Sonnenschein S, Schmidt FP, Mollnau H, Bock K, Ocete BQ, Munzel T, Theis C, Rostock T. Cardiac arrhythmias in patients with Danon disease. Europace. 2016 Oct 14. pii: euw215.

PubMed ID: 
27742774

Cone-rod dystrophy in Danon disease

Brodie S. Cone-rod dystrophy in Danon disease. Graefes Arch Clin Exp Ophthalmol. 2012 Mar 10. [Epub ahead of print].

PubMed ID: 
22407291

References

Konrad T, Sonnenschein S, Schmidt FP, Mollnau H, Bock K, Ocete BQ, Munzel T, Theis C, Rostock T. Cardiac arrhythmias in patients with Danon disease. Europace. 2016 Oct 14. pii: euw215.

PubMedID: 27742774

Brodie S. Cone-rod dystrophy in Danon disease. Graefes Arch Clin Exp Ophthalmol. 2012 Mar 10. [Epub ahead of print].

PubMedID: 22407291

Thiadens AA, Slingerland NW, Florijn RJ, Visser GH, Riemslag FC, Klaver CC. Cone-rod dystrophy can be a manifestation of Danon disease. Graefes Arch Clin Exp Ophthalmol. 2012 Jan 31. [Epub ahead of print]

PubMedID: 22290069

Laforet P, Charron P, Maisonobe T, Romero NB, Villard E, Sebillon P, Drouin-Garraud V, Dubourg O, Fardeau M, Komajda M, Eymard B. Charcot-Marie-Tooth features and maculopathy in a patient with Danon disease. Neurology. 2004 Oct 26;63(8):1535.

PubMedID: 15505188