Long‐term cognitive follow‐up in children treated for Maroteaux‐Lamy syndrome

Abstract

BackgroundIt remains unclear to what extent the brain is affected by Maroteaux-Lamy syndrome (MPS VI), a progressive lysosomal storage disorder. While enzyme replacement therapy (ERT) elicits positive effects, the drug cannot cross the blood–brain barrier. We therefore studied cognitive development and brain abnormalities in the Dutch MPS VI patient population treated with ERT.MethodsIn a series of 11 children with MPS VI (age 2 to 20 years), we assessed cognitive functioning and brain magnetic resonance imaging prospectively at the start of ERT and at regular times thereafter up to 4.8 years. We also assessed the children’s clinical characteristics, their siblings’ cognitive development, and their parents’ educational levels.ResultsThe patients’ intelligence scores ranged from normal to mentally delayed (range test scores 52–131). In 90 %, their scores remained fairly stable during follow-up, generally lying in the same range as their siblings’ test scores (median for patients = 104, median for siblings = 88) and comparing well with the parental educational levels. Native-speaking patients had higher intelligence test scores than non-native-speaking patients. Two patients, both with high baseline glycosaminoglycan levels in their urine and severe mutations in the arylsulfatase B gene, scored clearly lower than expected. Patients with pY210C performed best. Brain abnormalities were aspecific, occurring more in patients with severe symptoms.ConclusionOur study shows that cognitive development in MPS VI patients is determined not only by familial and social-background factors, but, in patients with a severe form of the disease, also by the disease itself. Therefore in patients with severe disease presentation cognition should be monitored carefully.Electronic supplementary materialThe online version of this article (doi:10.1007/s10545-015-9895-8) contains supplementary material, which is available to authorized users.

Clinical effectiveness of enzyme replacement therapy with galsulfase in mucopolysaccharidosis type VI treatment: Systematic review

“…The hearing function and the cognitive development remained stable after treatment . The other outcomes related to cardiac function, visual acuity, sleep apnea, and the size of the liver and spleen presented inconclusive results (Table ).…”

Craniosynostosis affects the majority of mucopolysaccharidosis patients and can contribute to increased intracranial pressure

“…In non-neuronopathic MPS patients, extensive GAG accumulation in the brain is not observed, and neurocognitive developmental is usually described as normal (Neufeld and Muenzer 2001 ; Valayannopoulos et al 2010 ). Interestingly, we previously described mild cognitive impairment in three MPS VI patients (Ebbink et al 2016 ). In this study, it is shown that two of these patients had pansynostosis and one had closure of two sutures before the age of 6 years (patient nos.…”

Netherton syndrome; neuropsychological and psychosocial functioning of child and adult patients and their parents

“…If there are stronger verbal possibilities than performance possibilities, problems may occur such as insufficiently balanced visual-constructive information processing (“seeing and then doing”), difficulty with practical tasks, not being able to oversee tasks at school, and work and organizing their own emotions/behavior ( Emmen, 2012 ; Van der Bergh, 2017 ). Disharmonic intelligence profiles and neurocognitive problems are known in other samples of pediatric conditions (asthma, prematurity, lysosomal-metabolic disease, meningococcal septic shock) defined by Ebbink et al (2016) , Irani et al (2017) , Larroque et al (2008) , and Vermunt et al (2009) and some of those conditions (e.g. metabolic and septic shock) have shown apparent abnormalities in the white matter of the brain ( Ebbink et al, 2016 ; Vermunt et al, 2009 ).…”

“…Disharmonic intelligence profiles and neurocognitive problems are known in other samples of pediatric conditions (asthma, prematurity, lysosomal-metabolic disease, meningococcal septic shock) defined by Ebbink et al (2016) , Irani et al (2017) , Larroque et al (2008) , and Vermunt et al (2009) and some of those conditions (e.g. metabolic and septic shock) have shown apparent abnormalities in the white matter of the brain ( Ebbink et al, 2016 ; Vermunt et al, 2009 ). Little is known about the underlying mechanisms which can explain disharmonic intelligence profiles in pediatric conditions, making it difficult to compare outcomes with the present findings.…”