eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Danon Disease: Follow-up

Author: Christopher C Erickson, MD, Associate Professor, Departments of Pediatrics and Internal Medicine, Electrophysiology and Pacing, University of Nebraska College of Medicine; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine
Coauthor(s): Janice L McAllister, MD, Assistant Professor, Department of Pediatrics, University of Nebraska College of Medicine; Consulting Staff, University of Nebraska Medical Associates, St Joseph Hospital, Children's Hospital of Omaha; Stanley J Radio, MD, Professor, Department of Pathology and Microbiology, University of Nebraska Medical Center
Contributor Information and Disclosures

Updated: May 22, 2008

Follow-up

Further Inpatient Care

  • Inpatient care is needed for patients with Danon disease who present with life-threatening arrhythmias or clinically significant CHF.
  • When the patient develops CHF due to the dilated form of the disease, inpatient medical care may be indicated to administer intravenous inotropic agents and diuretics.
  • When arrhythmias are noted, inpatient telemetry is helpful. Implantation of an ICD or pacemaker often necessitates an overnight admission with telemetry.
  • Inpatient care is usually not required to manage the neurologic symptoms of Danon disease.

Further Outpatient Care

  • Most of the cardiac care for patients with Danon disease can be provided in an outpatient setting.
    • This care should include routine echocardiography to monitor the progression of hypertrophy and to detect changes suggestive of decreased left ventricular function and evolution to dilated cardiomyopathy.
    • Holter monitoring should be followed up every 6-12 months depending on the patient's symptoms and degree of hypertrophy, as determined with echocardiography.
  • Male patients with Danon disease may require physical therapy for range-of-motion exercises and should be seen as needed by a pediatric neurologist. No medications cure or ameliorate the neuromuscular symptoms of Danon disease.

Deterrence/Prevention

  • Currently, no treatment prevents the onset of Danon disease. Early and repeated echocardiographic surveillance of young male relatives of anyone with Danon disease should be performed. Identification of a specific mutation in LAMP2 in a family may allow relatives to consider presymptomatic DNA testing after thorough genetic counseling.
  • Holter monitoring should also be performed when Danon disease is diagnosed.
  • An ICD should be implanted when clinically significant septal thickening of more than 30 mm is noted on echocardiography, when a poor increase in blood pressure is noted during exercise testing, when ventricular tachycardia is noted on Holter monitoring, or if the patient has a family history of sudden death, as is recommended for patients with hypertrophic cardiomyopathy (HCM).28 The data are insufficient to make a specific recommendation about ICDs in patients with Danon disease alone.
  • From a neurologic perspective, range-of-motion exercises help to prevent joint contractures as the skeletal muscles weaken.

Complications

  • Potential complications for this disease include syncope or sudden death before placement of an ICD.
  • As with other forms of dilated cardiomyopathy, low-flow states can pose a risk of intracardiac thrombus formation with the potential for stroke.
  • The onset of CHF symptoms can be abrupt and should initiate a discussion about and workup for cardiac transplantation.

Prognosis

  • Patients with Danon disease have a poor life expectancy.
    • The prognosis for male patients is poor. Most male patients die before their third decade from either a sudden cardiac arrhythmia or CHF.4
    • Female patients live to their fifth decade.4 Death can be the result of a cardiac arrhythmia or CHF.
  • Male patients have mild weakness of the skeletal muscle with slow or no deterioration over time.
    • These patients also are likely to have a learning disorder or mild mental retardation.4,8,12
    • Previously reported cases have not documented any deterioration in mental capacity over time.
  • See Mortality/Morbidity.

Patient Education

Miscellaneous

Medicolegal Pitfalls

  • In patients with hypertrophic cardiomyopathy (HCM), findings beyond cardiac involvement justify considering Danon disease and biopsy.
  • After the diagnosis is made, aggressive follow-up and possible intervention is indicated.
  • Failure to diagnose Danon disease can result in a potential failure to identify and treat a form of HCM that appears to be more malignant that other forms of HCM.

Special Concerns

  • These patients, particularly male patients, have an especially malignant form of HCM.
  • A confirmed diagnosis of Danon disease should prompt a review of life expectancy for all patients and a determination of their likelihood of needing an ICD and possible transplantation.
  • The diagnosis should also prompt an evaluation of immediate family members for the disease including genetic testing if possible.
 


More on Danon Disease

Overview: Danon Disease
Differential Diagnoses & Workup: Danon Disease
Treatment & Medication: Danon Disease
Follow-up: Danon Disease
Multimedia: Danon Disease
References
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References

  1. Arad M, Maron BJ, Gorham JM, et al. Glycogen storage diseases presenting as hypertrophic cardiomyopathy. N Engl J Med. Jan 27 2005;352(4):362-72. [Medline].

  2. Danon MJ, Oh SJ, DiMauro S, et al. Lysosomal glycogen storage disease with normal acid maltase. Neurology. Jan 1981;31(1):51-7. [Medline].

  3. Morisawa Y, Fujieda M, Murakami N, et al. Lysosomal glycogen storage disease with normal acid maltase with early fatal outcome. J Neurol Sci. Oct 8 1998;160(2):175-9. [Medline].

  4. Sugie K, Yamamoto A, Murayama K, et al. Clinicopathological features of genetically confirmed Danon disease. Neurology. Jun 25 2002;58(12):1773-8. [Medline].

  5. Maron BJ, Gardin JM, Flack JM, et al. Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary Artery Risk Development in (Young) Adults. Circulation. Aug 15 1995;92(4):785-9. [Medline].

  6. Charron P, Villard E, Sebillon P, et al. Danon's disease as a cause of hypertrophic cardiomyopathy: a systematic survey. Heart. Aug 2004;90(8):842-6. [Medline].

  7. Nishino I, Fu J, Tanji K, et al. Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature. Aug 24 2000;406(6798):906-10. [Medline].

  8. Yang Z, McMahon CJ, Smith LR, et al. Danon disease as an underrecognized cause of hypertrophic cardiomyopathy in children. Circulation. Sep 13 2005;112(11):1612-7. [Medline].

  9. Riggs JE, Schochet SS, Gutmann L, et al. Lysosomal glycogen storage disease without acid maltase deficiency. Neurology. Jul 1983;33(7):873-7. [Medline].

  10. Byrne E, Dennett X, Crotty B, et al. Dominantly inherited cardioskeletal myopathy with lysosomal glycogen storage and normal acid maltase levels. Brain. Jun 1986;109 (Pt 3):523-36. [Medline].

  11. Lacoste-Collin L, Garcia V, Uro-Coste E, et al. Danon's disease (X-linked vacuolar cardiomyopathy and myopathy): a case with a novel Lamp-2 gene mutation. Neuromuscul Disord. Nov 2002;12(9):882-5. [Medline].

  12. Fanin M, Nascimbeni AC, Fulizio L, et al. Generalized lysosome-associated membrane protein-2 defect explains multisystem clinical involvement and allows leukocyte diagnostic screening in Danon disease. Am J Pathol. Apr 2006;168(4):1309-20. [Medline].

  13. Laforet P, Charron P, Maisonobe T, et al. Charcot-Marie-Tooth features and maculopathy in a patient with Danon disease [case report]. Neurology. Oct 26 2004;63(8):1535. [Medline].

  14. Prall, F. R.; Drack, A.; Taylor, M.; Ku, L.; Olson, J. L.; Gregory, et al. Ophthalmic manifestations of Danon disease. Ophthalmology. 2006;113:1010-1013.

  15. Dworzak F, Casazza F, Mora M, et al. Lysosomal glycogen storage with normal acid maltase: a familial study with successful heart transplant. Neuromuscul Disord. May 1994;4(3):243-7. [Medline].

  16. Kashio N, Usuki F, Akamine T, et al. Cardiomyopathy, mental retardation, and autophagic vacuolar myopathy. Abnormal MRI findings in the head. J Neurol Sci. Sep 1991;105(1):1-5. [Medline].

  17. Echaniz-Laguna A, Mohr M, Epailly E, et al. Novel Lamp-2 gene mutation and successful treatment with heart transplantation in a large family with Danon disease. Muscle Nerve. Mar 2006;33(3):393-7. [Medline].

  18. Froissart R, Maire I. Danon Disease. Orphanet Encyclopedia. 2002. [Full Text].

  19. Konecki DS, Foetisch K, Zimmer KP, et al. An alternatively spliced form of the human lysosome-associated membrane protein-2 gene is expressed in a tissue-specific manner. Biochem Biophys Res Commun. Oct 13 1995;215(2):757-67. [Medline].

  20. Furuta K, Yang XL, Chen JS, et al. Differential expression of the lysosome-associated membrane proteins in normal human tissues. Arch Biochem Biophys. May 1 1999;365(1):75-82. [Medline].

  21. Tachi N, Tachi M, Sasaki K, et al. Glycogen storage disease with normal acid maltase: skeletal and cardiac muscles. Pediatr Neurol. Jan-Feb 1989;5(1):60-3. [Medline].

  22. Spirito P, Bellone P, Harris KM, et al. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med. Jun 15 2000;342(24):1778-85. [Medline].

  23. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. Jan 20 2005;352(3):225-37. [Medline].

  24. Young JB, Abraham WT, Smith AL, et al. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA. May 28 2003;289(20):2685-94. [Medline].

  25. Maron BJ, Ackerman MJ, Nishimura RA, et al. Task Force 4: HCM and other cardiomyopathies, mitral valve prolapse, myocarditis, and Marfan syndrome. J Am Coll Cardiol. Apr 19 2005;45(8):1340-5. [Medline].

  26. Maron BJ, Chaitman BR, Ackerman MJ, et al. Recommendations for physical activity and recreational sports participation for young patients with genetic cardiovascular diseases. Circulation. Jun 8 2004;109(22):2807-16. [Medline].

  27. Stuberg WA. Muscular dystrophy and muscular atrophy. In: Campbell SK, Vander Linden DW, Palisano RJ, eds. Physical Therapy for Children. 3rd ed. Philadelphia, Pa: WB Saunders;. 2005: 421-52.

  28. Maron BJ, Estes NA, Maron MS, et al. Primary prevention of sudden death as a novel treatment strategy in hypertrophic cardiomyopathy. Circulation. Jun 17 2003;107(23):2872-5. [Medline].

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Further Reading

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Keywords

Danon disease, Danon syndrome, Danon's disease, Danon's syndrome, lysosomal-associated membrane protein-2 deficiency, LAMP2, LAMP-2 deficiency, glycogen storage disease, glycogen-storage disease, lysosomal glycogen storage disease with normal acid maltase activity, hypertrophic cardiomyopathy with muscular dystrophy, HCM, hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome, WPW syndrome, idiopathic hypertrophic subaortic stenosis, IHSS, aortic stenosis, hypertension, Pompe disease, Fabry disease, maltase deficiency, dilated cardiomyopathy, skeletal myopathy, mental retardation, congestive heart failure, CHF, syncope, sudden death, learning disorder, maculopathy, hepatomegaly, splenomegaly, foot deformities, atrioventricular block, left bundle-branch block, bradycardia, ventricular tachycardia

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Contributor Information and Disclosures

Author

Christopher C Erickson, MD, Associate Professor, Departments of Pediatrics and Internal Medicine, Electrophysiology and Pacing, University of Nebraska College of Medicine; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine
Christopher C Erickson, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Cardiology, American Heart Association, Heart Rhythm Society, International Society for Holter and Noninvasive Electrocardiology, and Pediatric and Congential Electrophysiology Society
Disclosure: Nothing to disclose.

Coauthor(s)

Janice L McAllister, MD, Assistant Professor, Department of Pediatrics, University of Nebraska College of Medicine; Consulting Staff, University of Nebraska Medical Associates, St Joseph Hospital, Children's Hospital of Omaha
Janice L McAllister, MD is a member of the following medical societies: American Academy of Neurology and Child Neurology Society
Disclosure: Nothing to disclose.

Stanley J Radio, MD, Professor, Department of Pathology and Microbiology, University of Nebraska Medical Center
Stanley J Radio, MD is a member of the following medical societies: American Society of Clinical Pathologists, American Society of Cytopathology, College of American Pathologists, and International Academy of Pathology
Disclosure: Nothing to disclose.

Medical Editor

James Bowman, MD, Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago
James Bowman, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Pathologists, American Society of Human Genetics, Central Society for Clinical Research, and College of American Pathologists
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

David Flannery, MD, FAAP, FACMG, Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia
David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics
Disclosure: Nothing to disclose.

CME Editor

Paul D Petry, DO, FACOP, FAAP, Consulting Staff, Freeman Pediatric Care, Freeman Health System
Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association
Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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