Profound Intellectual Disabilities Research Articles

Novel SETBP1 D874V adjacent to the degron causes canonical schinzel–giedion syndrome: a case report and review of the literature

Schinzel-Giedion syndrome (SGS) is a severe multisystem disorder characterized by distinctive facial features, profound intellectual disability, refractory epilepsy, cortical visual impairment, hearing loss, and various congenital anomalies. SGS is attributed to gain-of-function (GoF) variants in the SETBP1 gene, with reported variants causing canonical SGS located within a 12 bp hotspot region encoding SETBP1 residues aa868-871 (degron). Here, we describe a case of typical SGS caused by a novel heterozygous missense variant, D874V, adjacent to the degron. The female patient was diagnosed in the neonatal period and presented with characteristic facial phenotype (midface retraction, prominent forehead, and low-set ears), bilateral symmetrical talipes equinovarus, overlapping toes, and severe bilateral hydronephrosis accompanied by congenital heart disease, consistent with canonical SGS. This is the first report of a typical SGS caused by a, SETBP1 non-degron missense variant. This case expands the genetic spectrum of SGS and provides new insights into genotype-phenotype correlations.

The influence of contextual factors on an intervention for people with disabilities from support persons’ and health personnel's perspectives: a focus group study

IntroductionContextual factors influence interventions in healthcare and pose a particular challenge in interventions designed for people with profound intellectual and multiple disabilities (PIMD). Exploring support persons’ and health personnel’s experience of an intervention may improve our understanding of the influence of contextual factors. Such exploration is important for revealing areas and focus points for future implementations. Therefore, the aim of this study is to explore support persons’ and health personnel’s experience of contextual factors during involvement in an intervention for people with PIMD.MethodsThis focus group study includes eight groups, comprising a total of 34 support persons and health personnel, at habilitation centres at four regions in central Sweden. Data were analysed inductively using a content analysis approach.ResultsThree themes emerged from the analysis of the informants’ perspectives on the contextual factors: (1) structure and support enhances intervention feasibility; (2) an intervention’s benefit for people with PIMD increases its acceptability; and (3) being engaged and involved increases support persons’ and health personnel’s motivation. Our findings show that the implementation of an intervention for people with PIMD should focus on the recipients of the intervention in its context, forming a clear communication plan. A training programme should be provided for the recipients and providers of the intervention.DiscussionFinally, the implementation process can be facilitated by creating space for staff to contribute and by encouraging participation and ownership for everyone involved. Using a co-design strategy can enable a shared responsibility to solve the identified challenges, while contributing to the development and design of future interventions for people with disabilities.

Parents’ tacit knowledge of their child with profound intellectual and multiple disabilities: A qualitative study

ABSTRACT Background Parents’ tacit knowledge plays an important role in the care of persons with profound intellectual and multiple disabilities (PIMD). As little is known about its nature and use, we aimed to explore this parental tacit knowledge. Method We conducted semi-structured interviews with parents (n = 11) about their tacit knowledge of their child, based upon video recordings they made of their child’s behaviour, and analysed the data thematically. Results Parents described their tacit knowledge as the capacity to read their child’s subtle signs, or to sense and “just know” their child’s situation. They had developed this knowledge because of their shared history of proximity and interaction and emphasised that it was crucial in ensuring their children’s needs are met. Conclusions We describe how parents’ tacit knowledge contributes to “good care” for persons with PIMD, interpret the implications for (medical) care practice, and discuss ways to deal with its limitations.

A novel pathogenic SLC12A5 missense variant in epilepsy of infancy with migrating focal seizures causes impaired KCC2 chloride extrusion.

The potassium-chloride co-transporter 2, KCC2, is a neuron-specific ion transporter that plays a multifunctional role in neuronal development. In mature neurons, KCC2 maintains a low enough intracellular chloride concentration essential for inhibitory neurotransmission. During recent years, pathogenic variants in the KCC2 encoding gene SLC12A5 affecting the functionality or expression of the transporter protein have been described in several patients with epilepsy of infancy with migrating focal seizures (EIMFS), a devastating early-onset developmental and epileptic encephalopathy. In this study, we identified a novel recessively inherited SLC12A5 c.692G>A, p. (R231H) variant in a patient diagnosed with severe and drug-resistant EIMFS and profound intellectual disability. The functionality of the variant was assessed in vitro by means of gramicidin-perforated patch-clamp experiments and ammonium flux assay, both of which indicated a significant reduction in chloride extrusion. Based on surface immunolabeling, the variant showed a reduction in membrane expression. These findings implicate pathogenicity of the SLC12A5 variant that leads to impaired inhibitory neurotransmission, increasing probability for hyperexcitability and epileptogenesis.

Family Resilience Affecting Well-Being of Families With a Child With Profound Intellectual and Multiple Disabilities.

Persons with profound intellectual and multiple disabilities (PIMD) have pervasive support needs, which are often managed by their families. By being resilient and positively adapting to this challenge, families may maintain a positive family quality of life (FQOL). We therefore aimed to understand how families with a child with PIMD experience their family resilience, and if and how it affects their FQOL. Participants were 64 parents of a person with PIMD from 44 families. Total family resilience, as well as most subscales received positive scores, and also had a significant positive effect on FQOL. These results provide more insight into the family dynamics of families with a child with PIMD, which should inform policies, and provided services for these families.

Paternalism, Supported Decision-Making and Expressive Respect

It has been argued by disability advocates that supported decision-making must replace surrogate, or substituted, decision-making for people with cognitive disabilities. From a moral perspective surrogate decision-making it is said to be an indefensible form of paternalism. At the heart of this argument against surrogate decision-making is the belief that such paternalistic action expresses something fundamentally disrespectful about those upon whom it is imposed: that they are inferior, deficient or child-like in some way. Contrary to this widespread belief, I will argue that surrogate decision-making often expresses more respect for people with life-long, ‘severe’ or ‘profound’ cognitive disabilities than does the adoption of supported decision-making. Specifically, I argue that in some cases supported decision-making can arguably express that people with cognitive disabilities lack equal moral value. I also argue that supported decision-making for people with profound intellectual disabilities can arguably express that they lack complex and rich inner lives. If our aim is to ensure our behaviour and practices express respect for people with life-long cognitive disabilities, then sometimes surrogate rather than supportive decision-making will be a better option.  

Activities of the Non-Public Primary School at the Aid for People with Disabilities Foundation for children and young people with multiple disabilities

This article presents the activities undertaken for the benefit of children and young people with multiple disabilities by those involved in the establishment and running of the Non-Public Primary School at the Foundation for Assistance to People with Disabilities. The historical aspect of the moment of initiation and continuous development of the establishment is presented, as well as the current aims and directions of its activities. The mission of the establishment is to prepare pupils, within the scope of their individual abilities and needs, to function independently in everyday life, as well as to develop, in a broad sense, their ability to build social relationships and communicate with others. At present, the school, thanks to its many years of experience, highly qualified, interdisciplinary staff and proven methods and forms of cooperation matched to the individual needs and capabilities of the child and his or her family, provides nearly a hundred students, including those with coupled disabilities and profound intellectual disabilities, with professional interactions in the field of motor, pedagogical, speech therapy and psychological therapy.

Parent-perceived autonomy-supportive experiences and basic psychological needs of people with complex support needs: Development and preliminary psychometric evaluation of two questionnaires.

Background: Understanding and supporting basic psychological needs of persons with complex support needs is important but difficult because of communicative challenges . We developed and tested questionnaires to obtain parents' perspectives on autonomy support and basic psychological needs of autonomy, competence, and relatedness. Method: Two parent-informant questionnaires were developed, administered, and subjected to psychometric property analyses. Participants were 63 Dutch parents of persons diagnosed with severe or profound intellectual and multiple disabilities. Results: Principal component analyses revealed a one-factor structure for the Parental Perceptions on Autonomy-Supportive Experiences questionnaire, while the Parental Perceptions on Basic Psychological Need Signals questionnaire yielded two-factors interpreted as Noticing Signals of Autonomy and Noticing Signals of Competence/Relatedness. Evidence for construct validity was found for both instruments. Conclusions: Preliminary evaluation of the new questionnaires is encouraging, but further validation with a larger sample size is warranted.

A case report of Pallister-Killian syndrome with an unusual mosaic supernumerary marker chromosome 12 with interstitial 12p13.1-p12.1 duplication.

Pallister-Killian syndrome (PKS) is a rare inherited disease with multiple congenital anomalies, profound intellectual disability, and the presence in the karyotype of sSMC - i(12)(p10). The frequency of PKS may be underestimated due to problems with cytogenetic diagnosis caused by tissue-specific mosaicism and usually a low percentage of peripheral blood cells containing sSMC. Such tissue-specific mosaicism also complicates a detailed analysis of the sSMC, which, along with the assessment of mosaicism in different tissues, is an important part of cytogenetic diagnosis in PKS. Unfortunately, a full-fledged diagnosis in PKS is either practically impossible or complicated. On the one hand, this is due to problems with the biopsy of various tissues (skin biopsy with fibroblast culture is most often used in practice); on the other - a low percentage of dividing peripheral blood cells containing sSMC, which often significantly complicates the analysis of its composition and organization. In the present study, a detailed analysis of sSMC was carried out in a patient with a characteristic clinical picture of PKS. A relatively high percentage of peripheral blood cells with sSMC (50%) made it possible to perform a detailed molecular cytogenetic analysis of de novo sSMC using chromosomal in situ suppression hybridization (CISS-hybridization), multicolor FISH (mFISH), multicolor chromosome banding (MCB), array CGH (aCGH), and quantitative real-time PCR (qPCR), and short tandem repeat (STR) - analysis. As a result, it was found that the sSMC is not a typical PKS derivative of chromosome 12. In contrast to the classical i(12)(p10) for PKS, the patient's cells contained an acrocentric chromosome consisting of 12p material. Clusters of telomeric repeats were found at the both ends of the sSMC. Furthemore, the results of aCGH and qPCR indicate the presence of interstitial 8.9Mb duplication at 12p13.1-p12.1 within the sSMC, which leads to different representations of DNA from different segments of 12p within cells containing sSMC. The obtained data raise the question of the instability of the sSMC and, as a consequence, the possible presence of additional rearrangements, which, in traditional cytogenetic analysis of patients with PKS, are usually described as i(12)(p10).

Expanding the genetic and phenotypic spectrum of TRAPPC9 and MID2-related neurodevelopmental disabilities: report of two novel mutations, 3D-modelling, and molecular docking studies.

Intellectual disabilities (ID) and autism spectrum disorders (ASD) have a variety of etiologies, including environmental and genetic factors. Our study reports a psychiatric clinical investigation and a molecular analysis using whole exome sequencing (WES) of two siblings with ID and ASD from a consanguineous family. Bioinformatic prediction and molecular docking analysis were also carried out. The two patients were diagnosed with profound intellectual disability, brain malformations such as cortical atrophy, acquired microcephaly, and autism level III. The neurological and neuropsychiatric examination revealed that P2 was more severely affected than P1, as he was unable to walk, presented with dysmorphic feature and exhibited self and hetero aggressive behaviors. The molecular investigations revealed a novel TRAPPC9 biallelic nonsense mutation (c.2920 C > T, p.R974X) in the two siblings. The more severely affected patient (P2) presented, along with the TRAPPC9 variant, a new missense mutation c.166 C > T (p.R56C) in the MID2 gene at hemizygous state, while his sister P1 was merely a carrier. The 3D modelling and molecular docking analysis revealed that c.166 C > T variant could affect the ability of MID2 binding to Astrin, leading to dysregulation of microtubule dynamics and causing morphological abnormalities in the brain. As our knowledge, the MID2 mutation (p.R56C) is the first one to be detected in Tunisia and causing phenotypic variability between the siblings. We extend the genetic and clinical spectrum of TRAPPC9 and MID2 mutations and highlights the possible concomitant presence of X-linked as well as autosomal recessive inheritance to causing ID, microcephaly, and autism.

Action priorities to facilitate planning of the transition to adulthood of young people with profound intellectual disability

Objectives It is essential for parents and professionals to be engaged in identifying and developing solutions that facilitate the transition to adulthood of young people with profound intellectual disability. However, most of them are dissatisfied in various ways with the current services available. To date, there is a paucity of literature guiding the development of solutions to meet the needs of young people with profound intellectual disability, their parents and their professionals. This study aimed to understand actions priorities to facilitate transition planning for young people with profound intellectual disability according to parents and professionals. Methods Parents and professionals from the education, health and community sectors participated in a three-stage prioritization process. Results The multistage methodological process for obtaining the viewpoints of parents and professionals involved in the planning of the transition to adulthood appear to be a relevant and realistic method. Both parents and professionals prioritized solutions in the informational and material support categories. They identified the creation of a transition guide and support for the development of meaningful activities for individuals with profound intellectual disability as the most feasible and important solutions. Both also highlighted the need to increase the number of places in day activity centres and to have a one-stop-shop for both information and guidance from a single actor during transition process. Conclusions Parents and professionals had similar action priorities, which pointed to the most interesting ways forward to develop in future studies of the transition to adulthood of young people with profound intellectual disability.

Developmental outcome of electroencephalographic findings in SYNGAP1 encephalopathy.

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

The effect of phonics skills intervention on early reading comprehension in an adolescent with autism: A longitudinal study

AbstractReading comprehension requires phonics skills, described as “blending phonemes in a word”. Adolescents diagnosed with Autism Spectrum Disorder (ASD) often experience poor reading comprehension. The aim of the present study was to explore if it is possible for an adolescent with ASD and intellectual disability to learn reading comprehension skills even without direct teaching, when the focus of the intervention is on teaching phonics skills. An adolescent with ASD, profound intellectual disability and limited behavioral repertoire participated in the study. The participant received intensive ABA‐based interventions according to University of California at Los Angeles‐Young Autism Project (UCLA‐YAP) model and intensive phonics training. Intervention data show emergence of early reading comprehension skills in terms of words/pictures matching and responding to written instructions. It is suggested that implementation of similar interventions could change the opportunities for people with autism who have limited behavioral repertoire and who did not begin an ABA‐based interventions until their adolescence.

Physical health conditions in young children with profound intellectual and multiple disabilities: The prevalence and associations between these conditions.

It is thought that physical health conditions start at a young age in people with profound intellectual and multiple disabilities (PIMD). Knowledge regarding the prevalence, associations and development of these physical health conditions could be used for purposes of prevention as well as appropriate care and support but is currently lacking. The aim of this study is to gain insight into the prevalence of physical health conditions and associations between these conditions in young children with PIMD. The study used cross-sectional data related to the physical health conditions of children with PIMD (n= 51, aged between 12 and 61 months). Data were collected in Belgium and in the Netherlands through a checklist filled in by primary caregiver(s). Physical health conditions were classified into categories by the 10th revision of the International Classification of Diseases and Related Health Problems (ICD-10) system. The number of physical health conditions and associations between them were analysed. The analysis focused on prevalence rates and associations represented by odds ratios (p< 0.05). A graphical model was estimated to represent dependencies and conditional dependencies between physical health conditions. We found a mean of 3.8 (range 1-8, SD 1.9) physical health conditions per child. Most of the physical health conditions were found in the ICD-10 chapter 'Nervous System', with hypotonia as the most frequent at 70.6%. Five significant large associations were found between spasticity-contractures (OR 9.54); circulatory system-contractures (OR 7.50); scoliosis-contractures (OR 10.25); hearing impairments-skin problems (OR 58.20) and obstipation-hypotonia (OR 19.98). This study shows that at a young age, multiple physical health conditions are present in children with PIMD. In addition, we found five associations between physical health conditions.

Clinical and genetic analysis of trichohepatoneurodevelopmental syndrome caused by a CCDC47 variant

Trichohepatoneurodevelopmental syndrome is an extremely uncommon autosomal recessive disorder resulting from variants in the CCDC47 gene, which encodes a Ca2+-binding endoplasmic reticulum (ER) transmembrane protein. To date, only four patients with CCDC47 deficiency have been reported, all of them with homozygous truncating CCDC47 variants. For this study, a Chinese family was recruited, which included a patient diagnosed with trichohepatoneurodevelopmental syndrome. Whole exome sequencing (WES) identified the proband's novel homozygous CCDC47 variation (NM_020198: c.634C > T(p.Arg212*). The variant was confirmed to be segregating in the proband and her unaffected relatives through Sanger sequencing. The patient described exhibited a clinical phenotype similar to that of patients with the CCDC47 variant. Compared to reported cases with CCDC47 pathogenic variants, our patients showed a novel complication of hearing impairment. In addition, brain abnormalities, small feet, bilateral hip dislocation, hip dysplasia, overlapping toes, pectus excavatum, scoliosis and narrow chest were not observed in our patient. We also examined five different variations and their corresponding phenotypes from five patients, both in current and previous research. Although some clinical manifestations of trichohepatoneurodevelopmental syndrome were highly variable, the most common phenotypes observed in these patients include microcephaly, profound intellectual disability, severe global development delay, pronounced growth restriction, hypotonia, woolly hair, facial dysmorphism, respiratory and visual abnormalities, gastrointestinal abnormalities, liver dysfunction, pruritus, skeletal and limb abnormalities, congenital heart defects and immunodeficiency. The present report is the first of a Chinese infant with homozygous variant in the CCDC47 gene. We expanded the genetic and phenotypic spectrum associated with trichohepatoneurodevelopmental syndrome.

Therapeutic Potential for Metabotropic Glutamate Receptor 7 Modulators in Cognitive Disorders.

Metabotropic glutamate receptor 7 (mGlu7) is the most highly conserved and abundantly expressed mGlu receptor in the human brain. The presynaptic localization of mGlu7, coupled with its low affinity for its endogenous agonist, glutamate, are features that contribute to the receptor's role in modulating neuronal excitation and inhibition patterns, including long-term potentiation, in various brain regions. These characteristics suggest that mGlu7 modulation may serve as a novel therapeutic strategy in disorders of cognitive dysfunction, including neurodevelopmental disorders that cause impairments in learning, memory, and attention. Primary mutations in the GRM7 gene have recently been identified as novel causes of neurodevelopmental disorders, and these patients exhibit profound intellectual and cognitive disability. Pharmacological tools, such as agonists, antagonists, and allosteric modulators, have been the mainstay for targeting mGlu7 in its endogenous homodimeric form to probe effects of its function and modulation in disease models. However, recent research has identified diversity in dimerization, as well as trans-synaptic interacting proteins, that also play a role in mGlu7 signaling and pharmacological properties. These novel findings represent exciting opportunities in the field of mGlu receptor drug discovery and highlight the importance of further understanding the functions of mGlu7 in complex neurologic conditions at both the molecular and physiologic levels. SIGNIFICANCE STATEMENT: Proper expression and function of mGlu7 is essential for learning, attention, and memory formation at the molecular level within neural circuits. The pharmacological targeting of mGlu7 is undergoing a paradigm shift by incorporating an understanding of receptor interaction with other cis- and trans- acting synaptic proteins, as well as various intracellular signaling pathways. Based upon these new findings, mGlu7's potential as a drug target in the treatment of cognitive disorders and learning impairments is primed for exploration.

Experiences of typically developing siblings of children with profound intellectual and multiple disabilities during the COVID-19 pandemic in Poland

Objectives This study aims to provide insight into the experiences of minor siblings of people with profound intellectual and multiple disabilities during the COVID-19 pandemic. Methods The research was based on information obtained from typically developing siblings of persons with profound intellectual and multiple disabilities. A total of 16 people were enrolled in the study. They were interviewed face-to-face from June to October, 2022. Analysis relied on open and axial coding performed by means of grounded theory methodology procedures. Results For the purpose of this study, the pandemic experiences cited by the siblings of people with profound intellectual and multiple disabilities were classified into several key domains: additional strain, feeling of frustration, reinforcement of relationship, further familiarization with sibling, sense of injustice, greater sympathy for parents, feeling of loneliness, gaining more confidence in one’s own capabilities, sense of maturity. Conclusions Siblings of people with profound intellectual and multiple disabilities recalled both positive and negative experiences during the COVID-19 pandemic, pointing out areas and facets of their lives and social relationships that either showed improvement or deterioration in their view.

Expansion of the neurodevelopmental phenotype of individuals with EEF1A2 variants and genotype-phenotype study.

Translation elongation factor eEF1A2 constitutes the alpha subunit of the elongation factor-1 complex, responsible for the enzymatic binding of aminoacyl-tRNA to the ribosome. Since 2012, 21 pathogenic missense variants affecting EEF1A2 have been described in 42 individuals with a severe neurodevelopmental phenotype including epileptic encephalopathy and moderate to profound intellectual disability (ID), with neurological regression in some patients. Through international collaborative call, we collected 26 patients with EEF1A2 variants and compared them to the literature. Our cohort shows a significantly milder phenotype. 83% of the patients are walking (vs. 29% in the literature), and 84% of the patients have language skills (vs. 15%). Three of our patients do not have ID. Epilepsy is present in 63% (vs. 93%). Neurological examination shows a less severe phenotype with significantly less hypotonia (58% vs. 96%), and pyramidal signs (24% vs. 68%). Cognitive regression was noted in 4% (vs. 56% in the literature). Among individuals over 10 years, 56% disclosed neurocognitive regression, with a mean age of onset at 2 years. We describe 8 novel missense variants of EEF1A2. Modeling of the different amino-acid sites shows that the variants associated with a severe phenotype, and the majority of those associated with a moderate phenotype, cluster within the switch II region of the protein and thus may affect GTP exchange. In contrast, variants associated with milder phenotypes may impact secondary functions such as actin binding. We report the largest cohort of individuals with EEF1A2 variants thus far, allowing us to expand the phenotype spectrum and reveal genotype-phenotype correlations.

Allogeneic hematopoietic cell transplantation for adult metachromatic leukodystrophy: a case series

AbstractMetachromatic leukodystrophy (MLD) is a rare genetic disorder caused by pathogenic variants of the ARSA gene, leading to a deficiency of the arylsulfatase A enzyme (ARSA) and consecutive accumulation of galactosylceramide-3-0-sulfate in the nervous system. The condition leads to severe neurological deficits and subsequently results in profound intellectual and motoric disability. Especially, the adult form of MLD, which occurs in individuals aged >16 years, poses significant challenges for treating physicians because of the rarity of cases, limited therapeutic options, and different allogeneic hematopoietic cell transplantation (allo-HCT) protocols worldwide. Here, we report the results of allo-HCT treatment in 4 patients with a confirmed adult MLD diagnosis. Bone marrow or mobilized peripheral progenitor cells were infused after a reduced intensity conditioning regime consisting of fludarabine and treosulfan. In 3 patients, allo-HCT was followed by an infusion of mesenchymal cells to further consolidate ARSA production. We observed a good tolerability and an increase in ARSA levels up to normal range values in all patients. A full donor chimerism was detected in 3 patients within the first 12 months. In a 1-year follow-up, patients with complete donor chimerism showed a neurological stable condition. Only 1 patient with an increasing autologous chimerism showed neurological deterioration and a decline in ARSA levels in the first year. In summary, allo-HCT offers a therapeutic option for reconstituting ARSA enzyme levels in adult patients with MLD, with tolerable side effects.

An analysis of visual functioning and cerebral visual impairments in children with profound intellectual and multiple disabilities

The aim of this study was to gain insight into the visual functioning of children with profound intellectuual and multiple disabilities (PIMD). A mixed methods study was performed, determining cross-sectional quantitative ophthalmological/orthoptic data, and qualitative observational data with a standardized research protocol (SRP) of 73 children with PIMD. Descriptive statistics and correlations were used for analyses of the data. Using ophthalmological data, 90.4% of the participants were found visually impaired. Based on the visual acuity (VA) testing, 49.6% of the participants had an impaired VA (&lt;0.3), and 15.3% could not be tested. Applying the SRP, profound cerebral visual impairment (CVI) was found in 43.8% of the participants; severe CVI in 28.8%; mild CVI in 13.7%; and no CVI in 12.3%. The correlation (Spearman’s rho) between CVI and severity of motor impairments was 0.61 ( p= .01). The results showed that visual impairment (VI) based on medical and ophthalmological data was present in nearly all of the participants with the highest prevalence among those with severe motor impairments. Providing specific information about visual functioning and the characteristics of CVI, using the SRP, may contribute to the individually adapted support of the development and partcipation of children with PIMD.