Intellectual and neurological functioning in Morquio syndrome (MPS IVa)

Abstract

Mucopolysaccharidosis type IVa (MPS IVa, Morquio syndrome OMIM #253000) is a lysosomal storage disease caused by deficiency in N-acetylgalactosamine-6-sulfatase (GALNS, EC 3.1.6.4; encoded by GALNS gene at 16q24.3). Unlike other MPS disorders involving excessive heparan and dermatan sulfate, Morquio syndrome has not been associated with neurological involvement nor with intellectual impairment as this disorder of keratan sulfate has been described as a purely visceral and skeletal disorder. Neurocognitive assessment was undertaken of MPS IVa patients with age appropriate intellectual tests as well as a Child Behaviour Checklist as part of clinical follow up. Available neuroimaging studies (MRI and MR spectroscopy) were reviewed. Whilst more than half of the overall IQ scores fell in the average range, scores for 3/8 children fell below average. A number of behavioural problems were highlighted, including anxiety/depression, attention and somatic complaints. Subtle neuroimaging abnormalities were demonstrated in over half of the children. These findings present a challenge to existing assumptions about the nature of Morquio A syndrome. A hypothesis regarding the potential role of calcium signalling is explored.

Diagnosis of Morquio-A patients in Mexico: How far are we from prompt diagnosis?

“…Since this syndrome has not any primary neurological involvement (17), the earlier abnormal signs in our population were seen around 4 years old and described as pigeon chest or thoracic deformities (including triangular cifosis, widened chest and thoracic asymmetry), however this is not corresponding with Bhattacharya, who describes this first manifestation evident as early as 6 to 12 months (11).…”

Avaliação neurológica e de neuroimagem em pacientes com mucopolissacaridoses

“…Entretanto, um estudo recente identificou um possível comprometimento cognitivo e alterações comportamentais previamente não descritas neste tipo de MPS (Davison et al 2012). …”

“…Em um estudo recente realizado por Davison e colaboradores, oito pacientes com diagnóstico de MPS IV A foram testados por meio de testes de coeficiente de inteligência, escala de avaliação comportamental preenchida pelos pais e exames de RM do crânio (Davison et al 2012). Os autores identificaram três pacientes (37% da amostra) com coeficiente de inteligência na faixa considerada limítrofe (entre 70 e 80, sendo o número esperado para esta faixa limítrofe na população geral 9,9%), dois pacientes com focos inespecíficos de alteração de sinal da RM e dois pacientes com espaços perivasculares proeminentes.…”

“…O acúmulo do QS poderia ocasionar a ativação de cascatas secundárias e interferir em outras vias bioquímicas como as vias de sinalização do cálcio, interferindo no metabolismo mitocondrial. Tais vias de sinalização do cálcio comprometidas já foram previamente descritas em outras doenças de depósito lisossomal e doenças neurodegenerativas (Vicencio et al 2010;Davison et al 2012). …”

“…Os pacientes com MPS tipo IV apresentam RM do encéfalo classicamente normal , ou são encontradas alterações sutis e inespecíficas, tais como pequenos focos de gliose no centro semi-oval, assimetria leve dos ventrículos laterais e espaços perivasculares alargados (Davison et al 2012). …”