Development of Sensory, Motor and Behavioral Deficits in the Murine Model of Sanfilippo Syndrome Type B

BACKGROUND: Mucopolysaccharidosis (MPS) IIIB (Sanfilippo Syndrome type B) is caused by a deficiency in the lysosomal enzyme N-acetyl-glucosaminidase (Naglu). Children with MPS IIIB develop disturbances of sleep, activity levels, coordination, vision, hearing, and mental functioning culminating in early death. The murine model of MPS IIIB demonstrates lysosomal distention in multiple tissues, a shortened life span, and behavioral changes. PRINCIPAL FINDINGS: To more thoroughly assess MPS IIIB in mice, alterations in circadian rhythm, activity level, motor function, vision, and hearing were tested. The suprachiasmatic nucleus (SCN) developed pathologic changes and locomotor analysis showed that MPS IIIB mice start their daily activity later and have a lower proportion of activity during the night than wild-type controls. Rotarod assessment of motor function revealed a progressive inability to coordinate movement in a rocking paradigm. Purkinje cell counts were significantly reduced in the MPS IIIB animals compared to age matched controls. By electroretinography (ERG), MPS IIIB mice had a progressive decrease in the amplitude of the dark-adapted b-wave response. Corresponding pathology revealed shortening of the outer segments, thinning of the outer nuclear layer, and inclusions in the retinal pigmented epithelium. Auditory-evoked brainstem responses (ABR) demonstrated progressive hearing deficits consistent with the observed loss of hair cells in the inner ear and histologic abnormalities in the middle ear. CONCLUSIONS/SIGNIFICANCE: The mouse model of MPS IIIB has several quantifiable phenotypic alterations and is similar to the human disease. These physiologic and histologic changes provide insights into the progression of this disease and will serve as important parameters when evaluating various therapies

Symptomatic asymmetry in the first six months of life: differential diagnosis

Asymmetry in infancy is a clinical condition with a wide variation in appearances (shape, posture, and movement), etiology, localization, and severity. The prevalence of an asymmetric positional preference is 12% of all newborns during the first six months of life. The asymmetry is either idiopathic or symptomatic. Pediatricians and physiotherapists have to distinguish symptomatic asymmetry (SA) from idiopathic asymmetry (IA) when examining young infants with a positional preference to determine the prognosis and the intervention strategy. The majority of cases will be idiopathic, but the initial presentation of a positional preference might be a symptom of a more serious underlying disorder. The purpose of this review is to synthesize the current information on the incidence of SA, as well as the possible causes and the accompanying signs that differentiate SA from IA. This review presents an overview of the nine most prevalent disorders in infants in their first six months of life leading to SA. We have discovered that the literature does not provide a comprehensive analysis of the incidence, characteristics, signs, and symptoms of SA. Knowledge of the presented clues is important in the clinical decision making with regard to young infants with asymmetry. We recommend to design a valid and useful screening instrument