Neuropsychological and neuropsychiatric disease spectrum in Single Large Scale Mitochondrial Deletions

Barbara Siri ¹ Benedetta Greco ² Stefania Caviglia ² Michela Grasso ² Daria Diodato ⁴ Carlo Dionisi Vici ¹ Stefano Vicari ³ Francesco Demaria ³ Diego Martinelli ¹

¹Division of Metabolism Bambino Gesu Children Hospital IRCCS, Italy
²Unit of Clinical Psychology Department of Neurosciences Bambino Gesu Children Hospital IRCCS, Italy
³Child and Adolescent Neuropsychiatry Unit Department of Neuroscience Bambino Gesu Children Hospital IRCCS, Italy
⁴Laboratory of Molecular Medicine, Unit of Muscular and Neurodegenerative Disorders Bambino Gesu Children Hospital IRCCS, Italy

Background

Single Large Scale Mitochondrial Deletions (SLSMDs), Pearson (PS), Kearns Sayre syndrome (KSS) and Chronic Progressive External Ophthalmoplegia (CPEO), represent a disease spectrum with multisystem involvement. Cognitive impairment and psychiatric symptoms have been rarely described in children/adolescents with MD with only anecdotal reports in SLSMDs.

Methods

Twelve SLSMDs (2 PS, 10 KSS) patients, aged from 5 to 23 years, were systematically assessed though neuropsychiatric evaluation, cognitive profile, and adaptive functioning. Results were also correlated to Newcastle Mitochondrial Adult (NMDAS)/Paediatric Disease Scale (NPMDS).

Results

In our cohort, intellectual functioning ranged from normal/borderline (n=5) to low, with mild (n=2), moderate (n=2) and severe (n=2) intellectual disability (ID). The severity of IQ correlated with a higher score at NMDAS/NPMD and disability scales. A higher verbal comprehension (median 86; 70-94), perceptual reasoning (79; 55-90) and working memory (79; 56-89) indexes were observed respect to low-speed processing (55; 49-59). General adaptive composite score was normal/borderline in 58%, while mild to moderate adaptive deficits were evidenced in 33%. Subdomains showed normal communication and socialization with impairment in daily living skills. Neuropsychiatric assessment with K-SADS-PL and CY-BOCS highlighted an OC disorder with compulsive hand washing in 66% of patients, from severe (n=2), moderate (n=3) to mild (n=3) disease and behaviours of hoarding and symmetry.

Conclusions

This study showed different levels of ID that paralleled the disease progression with a higher impairment in motor, hearing, and vision. Verbal, reasoning and working memory were normal in pts with normal/borderline IQ to mild ID, while impairment in speed processing emerged in all pts. Among psychiatric symptoms, an unreported peculiar trait of obsessive-compulsive behaviour with compulsive hand washing was also identified.