Degeneration of speech, language, and hearing in a patient with mucopolysaccharidosis VII

doi:10.1016/0165-5876(90)90215-D

International Journal of Pediatric Otorhinolaryngology

Volume 19, Issue 2, June 1990, Pages 97-107

https://doi.org/10.1016/0165-5876(90)90215-D Get rights and content

Abstract

Mucopolysaccharidosis VII (MPS-VII) is probably the rarest of the mucopolysac-charidoses; literature reveals only 20 cases. We have had the opportunity to study and treat such a child in our clinic, and this paper documents his speech, language, and hearing. Results demonstrated a delay with respect to his chronological age in all cognitive, linguistic, and social domains. He had a mixed hearing loss which could have contributed to his diminishing speech and language abilities; he had chronic otitis media. After 59 h of speech and language intervention (over a period of 19 months), primarily for language treatment, standardized tests revealed that his scores had decreased over time. During this period, both his speech production and his hearing got poorer. At about the time of his 8th birthday, he underwent a permanent tracheostomy, altering further therapy. Although MPS-VII is a very rare disorder, what has been learned here may apply to other MPSs and even to other multiply handicapped patients. We hope that the presentation of our findings may assist others when confronted with complex, degenerative disorders.

References (19)

W.S. Sly et al.
Beta-glucuronidase deficiency: report of clinical, radiologic, and biochemical features of a new mucopolysaccharidosis
J. Pediatr.
(1973)
B.A. Bracken
R. Brown
E. Carrow-Woolfolk
R.F. Debose et al.
L.M. Dunn et al.
L. Fisch
Syndromes associated with hearing loss
J.B. Fudala
D.L. Hendrick et al.

There are more references available in the full text version of this article.

Cited by (20)

Neuropsychology assessment and outcomes in adult mucopolysaccharidosis – A systematic review as the first step to service development in a large tertiary Lysosomal Storage Disorders centre
2023, Molecular Genetics and Metabolism
Citation Excerpt :
Yet adults with MPS have received limited attention in the literature, and hence little guidance exists on the clinical management of cognitive and psychological difficulties faced by these patients and their families. MPS I, II, III and VII involve progressive central nervous system (CNS) disease, causing cognitive impairment, behavioural abnormalities, sleep problems and/or seizures [3–9], psychosis, anxiety, depression, and autistic spectrum disorder [3,10]. Neuropsychological abnormalities and mental health problems have also been found in attenuated forms of MPS I, II, III [11], MPS IV and in MPS VI [12–15], and in some cases may still manifest significant cognitive impairments [16].
A systematic review of Randomised Controlled Trials in adult mucopolysaccharidoses (MPSs) was conducted to inform neuropsychology service development at a large tertiary Lysosomal Storage Diseases centre. Studies including psychological endpoints for cognition, mood, and quality of life were reviewed. Forty-eight studies met the inclusion criteria for full text review. Of the 48 studies, 44% (21/48) included adult participants, while psychological endpoints were used in 52% (25/48) for cognition, 11% (5/48) for mood, and 69% (33/48) for quality of life. Five studies included both adult participants and relevant psychological endpoints. Risk of bias ratings were ‘high’ for two studies, while two studies received a rating of ‘some concerns’, and the last study a ‘low’ risk of bias rating. The evidence base for psychological outcomes in adult MPS disorders is limited and insufficient for guiding neuropsychology service development. Data on the psychosocial effects of MPS across the lifespan will be crucial for planning service development and supporting the neuropsychological needs of adult patients and their families.
Issues of COVID-19-related distance learning for children with neuronopathic mucopolysaccharidoses
2021, Molecular Genetics and Metabolism
The COVID-19 pandemic has impacted the education of children around the world, forcing a large proportion of teaching to be carried out remotely. The implications of this disruption have yet to be fully elucidated, but initial assessments suggest that COVID-19-related school closures and reliance on virtual learning may have a long-term negative impact on educational attainment and future earnings as well as life expectancy of children in the United States. Among children with neurodegenerative disorders, such as neuronopathic mucopolysaccharidoses (MPS disorders), the effects of the pandemic are likely to be even greater. We aim to shine a spotlight on the impact of COVID-19 on the education, treatment and general wellbeing of children and families affected by MPS disorders by highlighting the important role that educators and therapists play in supporting the neurocognitive function and quality of life of children with neuronopathic MPS disorders. This article will serve as a resource that caregivers, educators, clinicians and therapists can use when considering how best to advocate for children with neuronopathic MPS disorders in circumstances where in-school teaching or in-clinic treatment is compromised or not possible. Given that the current pandemic is likely to have a prolonged course and impact and that similar epidemics and pandemics are a near certainty in the future, it is essential that steps are taken to support the learning and care of children with neuronopathic MPS disorders. We must prioritize strategies to safely resume this fragile community's access to in-person education and supportive care, and to address gaps that have emerged during prolonged pauses in access, whenever possible.
Therapy development for the mucopolysaccharidoses: Updated consensus recommendations for neuropsychological endpoints
2020, Molecular Genetics and Metabolism
Citation Excerpt :
The progressive somatic manifestations of MPS disorders vary, but can include coarse facies, hepatosplenomegaly, skeletal and joint abnormalities and cardiorespiratory disease [1]. CNS functional involvement includes progressive cognitive impairment (in MPS I, II, III and VII), behavioral abnormalities, sleep problems and/or seizures [1–9]. These progressive and lethal MPS disorders are described as ‘neuronopathic’.
Neurological dysfunction represents a significant clinical component of many of the mucopolysaccharidoses (also known as MPS disorders). The accurate and consistent assessment of neuropsychological function is essential to gain a greater understanding of the precise natural history of these conditions and to design effective clinical trials to evaluate the impact of therapies on the brain. In 2017, an International MPS Consensus Panel published recommendations for best practice in the design and conduct of clinical studies investigating the effects of therapies on cognitive function and adaptive behavior in patients with neuronopathic mucopolysaccharidoses. Based on an International MPS Consensus Conference held in February 2020, this article provides updated consensus recommendations and expands the objectives to include approaches for assessing behavioral and social-emotional state, caregiver burden and quality of life in patients with all mucopolysaccharidoses.
Epilepsy in mucopolysaccharidosis disorders
2017, Molecular Genetics and Metabolism
Citation Excerpt :
In addition, neurocognitive decline is observed in the neuronopathic forms of MPS I (Hurler [MPS IH]), MPS II, and MPS VII, and all MPS III phenotypes, although with varying severity [7,8]. In these patients, accumulation of GAGs in the brain, in particular heparan sulfate, is thought to trigger neuroinflammation, altered neuronal signaling, and neuronal cell death [9–12], which can lead to neurological manifestations such as impaired cognition, behavioral problems, and epileptic seizures [1,2,8,13–20]. Epilepsy is a neurological condition resulting from changes in the electrical functioning of the brain.
The mucopolysaccharidosis (MPS) disorders are caused by deficiencies of specific lysosomal enzymes involved in the catabolism of glycosaminoglycans (GAGs). The resulting GAG accumulation in cells and tissues throughout the body leads to progressive multi-organ dysfunction. MPS patients present with several somatic manifestations, including short stature, musculoskeletal abnormalities, and cardiorespiratory dysfunction, and several primary and secondary neurological signs and symptoms. Epileptic seizures are neurological signs of MPS thought to develop due to accumulation of GAGs in the brain, triggering alterations in neuronal connectivity and signaling, and release of inflammatory mediators. The amount of literature on the prevalence, pathophysiology, clinical features, and management of epileptic seizures in patients with MPS is limited. This review discusses current knowledge on this topic, as well as two case examples, presented and discussed during a closed meeting on MPS and the brain among an international group of experts with extensive experience in managing and treating MPS.
Practical management of behavioral problems in mucopolysaccharidoses disorders
2017, Molecular Genetics and Metabolism
Citation Excerpt :
Patients with MPS IV and VI can present with secondary neurological complications, such as spinal cord compression and hydrocephalus, but have normal cognitive development [1–5]. Patients with MPS I, II, III, and VII often show primary neurological manifestations such as developmental delay, impaired cognitive functioning, behavioral problems, sleep disturbances, and seizures [1,6–12]. Although the main GAGs accumulating in each of these four MPS disorders are incomplete products from heparan sulfate degradation [2], behavioral problems differ considerably among them.
The mucopolysaccharidosis (MPS) disorders are caused by deficiencies of specific lysosomal enzymes, resulting in progressive glycosaminoglycan (GAG) accumulation in cells and tissues throughout the body. Excessive GAG storage can lead to a variety of somatic manifestations as well as primary and secondary neurological symptoms. Behavioral problems (like hyperactivity, attention difficulties, and severe frustration) and sleeping problems are typical primary neurological symptoms of MPS caused by GAG accumulation in neurons, and are frequently observed in patients with MPS I, II, III, and VII. As these problems often place a significant burden on the family, proper management is important. This review summarizes current insights into behavioral and sleeping problems in MPS disorders and the most optimal management approaches, as presented and discussed during a meeting of an international group of experts with extensive experience in managing and treating MPS.
Assessments of neurocognitive and behavioral function in the mucopolysaccharidoses
2017, Molecular Genetics and Metabolism
Citation Excerpt :
In addition to a variety of somatic clinical manifestations that vary considerably between and within MPS types, patients with rapidly progressing/severe MPS I (Hurler [IH]), II (neuronopathic type), III, and VII (all associated with accumulation of heparan sulfate) show involvement of the central nervous system (CNS) [1,3,4]. CNS indicators include cognitive impairment in the forms of MPS mentioned above, and behavioral abnormalities, sleep problems, and/or seizures in select forms [1,4–11]. Because of the debilitating nature of cognitive impairment in MPS patients, and the substantial impact on the lives of both the patients and their families, it is considered a relevant symptom for improvement when developing therapies.
The mucopolysaccharidoses (MPS) are a group of rare, inherited lysosomal storage disorders in which accumulation of glycosaminoglycans (GAGs) leads to progressive tissue and organ dysfunction. In addition to a variety of somatic signs and symptoms, patients with rapidly progressing MPS I (Hurler), II, III, and VII can present with significant neurological manifestations, including impaired cognitive abilities, difficulties in language and speech, behavioral abnormalities, sleep problems, and/or seizures. Neurological symptoms have a substantial impact on the quality of life of MPS patients and their families. Due to the progressive nature of cognitive impairment in these MPS patients, neurocognitive function is a sensitive indicator of disease progression, and a relevant outcome when testing efficacy of therapies for these disorders. In order to effectively manage and develop therapies that address neurological manifestations of MPS, it is important to use appropriate neurocognitive assessment tools that are sensitive to changes in neurocognitive function in MPS patients.
This review discusses expert opinions on key issues and considerations for effective neurocognitive testing in MPS patients. In addition, it describes the neurocognitive assessment tools that have been used in clinical practice for these patients. The content of this review is based on existing literature and information from a meeting of international experts with extensive experience in managing and treating MPS disorders.

View all citing articles on Scopus

^☆: Presented at the annual meeting of the Society for Ear, Nose and Throat Advances in Children, New York, December 1988.

^†: Deceased December 1989.

View full text

Research reportDegeneration of speech, language, and hearing in a patient with mucopolysaccharidosis VII☆

Abstract

J. Pediatr.

Syndromes associated with hearing loss

Research report
Degeneration of speech, language, and hearing in a patient with mucopolysaccharidosis VII☆