Psychiatric and cognitive characteristics of individuals with Danon disease (LAMP2 gene mutation)

• Published in: American journal of medical genetics. Part A 2017-09, Vol.173 (9), p.2461-2466
• Main Authors: Yardeni, Maya, Weisman, Omri, Mandel, Hanna, Weinberger, Ronnie, Quarta, Giovanni, Salazar‐Mendiguchía, Joel, Garcia‐Pavia, Pablo, Lobato‐Rodríguez, Maria José, Simon, Lourdes Fajardo, Dov, Freimark, Arad, Michael, Gothelf, Doron
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anxiety; Cardiomyopathy; Cognition; Cognitive ability; Danon disease; Executive function; Female; Genetic Diseases, X-Linked; Glycogen Storage Disease Type IIb - genetics; Glycogen Storage Disease Type IIb - physiopathology; Glycogen Storage Disease Type IIb - psychology; Humans; Intellectual disabilities; Intellectual Disability - genetics; Intellectual Disability - physiopathology; Intellectual Disability - psychology; LAMP2; Lysosomal-Associated Membrane Protein 2 - genetics; Male; Membrane proteins; Middle Aged; Mood; Mutation; Myopathy; Point mutation; psychiatric comorbidities; Wolff‐Parkinson‐White syndrome; Young Adult
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.38320

Danon disease (DD) is a rare X‐linked disorder caused by loss‐of‐function mutations in the LAMP2 gene, which encodes lysosome‐associated membrane protein. It is characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. Whereas the molecular and pathophysiological mechanisms underlying this disorder have been previously reported and continue to be explored, the cognitive deficits and psychiatric comorbidities manifested in DD remain an understudied topic. We systematically assessed cognitive abilities and psychiatric comorbidities in 13 males and females. Most of the participants in our cohort (n = 9; 75%) had an IQ score within the normal range, while only one participant had intellectual disability. Participants’ performance on the Cognitive Neuropsychiatric Battery (CNB) showed only mildly impaired cognitive abilities in most modules, except in the executive functioning test, which was low compared to healthy controls. Of note, 69% of the participants met criteria for at least one psychiatric disorder, mainly mood and anxiety disorders, occurring alone or in combination in the same patient. The results of the present study challenge earlier reports suggesting that mental retardation is a core constituent in DD. Of importance, it underscores the need to refer Danon patients to psychiatric assessment.