Danon disease presenting with transient stroke-like weakness in a young woman: a case report

TL;DR

A young woman with stroke-like symptoms was diagnosed with Danon disease, a rare genetic disorder, highlighting the importance of cardiac imaging and genetic testing for accurate diagnosis.

Contribution

This case report highlights the under-recognized neurological and cardiac manifestations of Danon disease in female carriers.

Findings

A 27-year-old woman presented with transient stroke-like weakness and was diagnosed with Danon disease via genetic testing.

Cardiac imaging and elevated biomarkers revealed significant heart dysfunction consistent with Danon disease.

The case emphasizes the need for multimodal cardiac evaluation and genetic analysis in atypical stroke presentations.

Abstract

Danon disease is a rare X-linked dominant lysosomal storage disorder caused by lysosome-associated membrane protein 2 (LAMP2) deficiency. Female carriers demonstrate highly variable penetrance, and neurological manifestations are under-recognized, which delays diagnosis and targeted management.

A 27-year-old woman presented with sudden-onset left-sided weakness that resolved within three weeks. Initial magnetic resonance imaging demonstrated a right basal ganglia infarction with distal right middle cerebral artery narrowing, and she received dual antiplatelet therapy and statins. When she was referred for etiologic evaluation, physical and neurological examinations were unremarkable, yet N-terminal pro-B-type natriuretic peptide and cardiac troponin I levels were elevated. Transthoracic echocardiography revealed left ventricular dilation with global hypokinesia (ejection fraction 30%). Right heart contrast echocardiography excluded patent foramen ovale, whereas 24 h Holter monitoring captured frequent atrial and ventricular ectopy with short ventricular tachycardia runs. Cardiac magnetic resonance showed markedly reduced systolic function (left ventricular ejection fraction 21%) and mid-wall late gadolinium enhancement, while myocardial perfusion imaging confirmed global hypoperfusion. Whole-exome sequencing identified a heterozygous LAMP2 frameshift variant (c.1079_1083delGAAAG; p.Gly360Valfs*11), which was validated by Sanger sequencing. Cascade testing revealed a hemizygous carrier son and wild-type parents. She was treated with contemporary heart failure therapy, oral dabigatran for presumed cardioembolic stroke, and listed for heart transplantation.

This case underscores that Danon disease in women may initially mimic cryptogenic stroke. Multimodality cardiac imaging combined with genetic analysis is crucial for recognizing atypical presentations and guiding anticipatory heart failure management.

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