Association of somatic burden of disease with age and neuropsychological measures in attenuated mucopolysaccharidosis types I, II and VI

Abstract

IntroductionThe mucopolysaccharidoses (MPSs) are a group of rare genetic lysosomal disorders with progressive multisystem involvement. An MPS-specific physical symptom scale was developed and introduced a Physical Symptom Score (PSS) to quantify the somatic disease burden across MPS I, II and VI.HypothesisSomatic burden of disease in patients with attenuated MPS I, II and VI as measured by the PSS will be positively associated with age and negatively associated with neuropsychological functions [i.e. full scale intelligence quotient (FSIQ) and attention].Materials and methodsForty-eight patients with attenuated MPS I (n = 24), II (n = 14), and VI (n = 10) aged 6 to 32 years on enzyme replacement therapy who were enrolled in “Longitudinal Studies of Brain Structure and Functions in MPS Disorders” across seven centers. Somatic disease burden was measured by the PSS. Neuropsychological functions were measured by the Wechsler Abbreviated Scale of Intelligence (WASI) and Test of Variables of Attention (TOVA).ResultsPSS was positively associated with age in attenuated MPS I (P < 0.001), MPS II (P < 0.01) and MPS VI (P < 0.05). There was a negative association of PSS with FSIQ in attenuated MPS I (P < 0.001) and in MPS VI (P < 0.001) but not with MPS II. Although attention scores were below average in all groups, a significant negative association between PSS and one measures of sustained attention (TOVA d prime) was found only in MPS VI.ConclusionsPhysical Symptom Score increased with age in attenuated MPS I, II and VI, reflecting progressive somatic burden of disease despite treatment with enzyme replacement therapy. Furthermore, the association of increased somatic disease burden with decreased neurocognitive ability suggests that both measures reflect disease severity and are not independent.

Neurobehavioral phenotypes of neuronopathic mucopolysaccharidoses

“…The extent of systemic disease burden may act as a predictor of cognitive performance in patients with attenuated MPS I. Recently, Ahmed et al [ 25 ] demonstrated that, in attenuated MPS I Hurler/Scheie (HS) and MPS IS, somatic disease burden measured by the Physical Symptom Score (PSS) was negatively associated with cognitive level (full-Scale IQ) ( p < 0.001), indicative that both measures reflect disease severity [ 25 ]. In addition, physical disease and sensorial defects cause functional impairment and reduce academic performances in attenuated MPS I individuals.…”

Disease burden, management patterns and multidisciplinary clinical approaches for patients with MPS IVA and VI in selected Latin American Countries

“…ERT has proven to be clinically effective in MPS patients, demonstrating an improvement in their range of motion, respiratory functions, cardiac functions, hearing, visual acuity, pain control and QoL [ [19] , [20] , [21] ]. Currently, elosulfase alfa and galsulfase are the only licensed ERT for patients with MPS-IVA and MPS-VI, respectively [ [22] , [23] , [24] , [25] , [26] ].…”

Avaliação do equilí­brio e risco de queda em pacientes com mucopolissacaridose VI

“…A Mucopolissacaridose VI (MPS VI), também conhecida como Síndrome de Maroteaux-Lamy, é uma doença rara, hereditária, autossômica recessiva, com mutação no gene ARSB, caracterizada pela deficiência na enzima lisossomal arisulfatase B, responsável pela degradação do dermatan sulfato, com isso progressivamente é acumulado o substrato intracelular, provocando as complicações multissistêmicas dos portadores [1][2][3][4][5][6][7][8][9].…”

“…Afeta ambos os sexos e a incidência mundial varia de 1: 230.000 a 1: 300.000 nascidos/vivos [6]. A MPS VI tem maiores registros no continente Europeu e América Latina, em particular em Portugal e no Brasil, sendo isto atribuído a distribuição migratória [8].…”

“…A variabilidade mutacional produz diversidade do fenótipo [2], provocando diferentes manifestações clinicas, como: baixa estatura, face infiltrada, dolicocefalia, hidrocefalia, defeito vertebral (beaking anterior), hipoplasia anterior da vértebra, compressão medular espinhal, giba toracolombar, picnodisostose, contraturas musculares graves, deformações ósseas, glaucoma, degeneração da retina, atrofia da retina, opacidade da córnea, complicações respiratórias, doenças cardíacas, hepatoesplenomegalia, perda ou diminuição da audição, hérnias inguinais, hipertrofia gengival, má oclusão dentária e hirsutismo [4][5][6][7]. Normalmente os sinais e sintomas são instalados entre o primeiro e o segundo anos de vida [10,12,13].…”