CASE REPORT Danon Disease in an Asymptomatic Woman: A Five-Year Follow Up

she was diagnosed with acute myocarditis. Patient was referred to a specialized HF center, where a Doppler echocardiography was performed, confirming the findings of HC (Figure 2), and revealing slight obstruction of the outflow pathway, and a Wolff-Parkinson-White (WPW) preexcitation pattern. The patient had elevated and stable levels of troponin I (7.74ng/dL), and natriuretic peptide (BNP) levels of 401 pg/mL six months after admission for chest pain. The patient underwent genetic testing; a new mutation NP_002285.1:p.Asn242Thrfs*41 compatible with DD was identified, and referred as accessory pathway (VA) ablation due to the WPW-type preexcitation.


Introduction
Danon disease (DD) 1 is a rare, dominant X-linked disease caused by mutation of the LAMP2 gene, which encodes a lysosome-associated membrane glycoprotein, thereby affecting lysosomal deposition. DD is characterized by a classic triad of cardiomyopathy (featured by hypertrophic cardiomyopathy [HC]), skeletal myopathy, and cognitive changes. While female patients tend to have milder phenotypic manifestations, an isolated cardiac involvement, in addition to a later onset of symptoms, without the need for heart transplantation before the fourth decade of life, male patients commonly have the presentation of the classic triad of disease. 2 The clues of the involvement of HC with preexcitation and persistent increased troponin I in these individuals are related to the process of autophagy that contributes to cardiac remodeling. 3 However, there is still no specific treatment for DD. The approach to cardiac manifestations includes implantable cardioverter defibrillator (ICD) and ablation to improve symptoms and decrease the risk of sudden death. In cases of advanced heart failure (HF), heart transplantation is an effective and safe measure. Studies for gene therapy are currently in progress. 4,5 Considering the small number of cases described in the literature about DD and the gap in knowledge for an earlier approach, we aimed to describe the case of a patient with incidental diagnosis of DD, presenting a mutation not previously described in the literature and its five-year follow-up.

Case description
A female 23-year-old Caucasian patient, only daughter of a no consaguineous couple, was incidentally diagnosed with HC at 18 years of age during the preoperative period of an orthopedic surgery and confirmed by cardiac resonance. The parents were asymptomatic, with normal echocardiogram.
At the age of 20, she was admitted to the emergency department with atypical chest pain, and no other findings at physical examination, and laboratory tests showed an increase in troponin I (6ng/dL). She underwent a new cardiac magnetic resonance imaging confirming the diagnosis of CH with delayed gadolinium enhancement (Figure 1). At the time, she was diagnosed with acute myocarditis.
Patient was referred to a specialized HF center, where a Doppler echocardiography was performed, confirming the findings of HC (Figure 2), and revealing slight obstruction of the outflow pathway, and a Wolff-Parkinson-White (WPW) preexcitation pattern. The patient had elevated and stable levels of troponin I (7.74ng/dL), and natriuretic peptide (BNP) levels of 401 pg/mL six months after admission for chest pain. The patient underwent genetic testing; a new mutation NP_002285.1:p.Asn242Thrfs*41 compatible with DD was identified, and referred as accessory pathway (VA) ablation due to the WPW-type preexcitation.  Since then, the patient has been asymptomatic, undergoing cardiac rehabilitation and treatment with beta-blockers. There has been no ICD firing since its implantation, in addition to normal renal, hepatic, ophthalmic and neurological functional tests. The patient has been followed by the departments of clinical genetics, cardiology, and arrhythmology, and received psychological support for anxiety disorder.
In the last months she has been in isolation due to the COVID-19 pandemic and routinely performed physical activities and in telemedicine consultation. The temporal progression of the events were described in Tablet 1.   Finally, genetic testing should be incorporated into clinical practice for congenital heart disease.

Potential Conflict of Interest
No potential conflict of interest relevant to this article was reported.

Sources of Funding
There were no external funding sources for this study.

Study Association
This study is not associated with any thesis or dissertation work.

Ethics approval and consent to participate
This article does not contain any studies with human participants or animals performed by any of the authors.