Refining Ounce-Equivalents Using the EAA-9 Approach for Protein Scoring and Dietary Guidance.

Background: The USDA Protein Food Ounce-equivalents are designed to identify plant sources of protein foods and provide serving size substitutions. While the ounce-equivalent concept is simple, it fails to generate equivalent exchanges for protein or essential amino acids (EAAs).

Objective: To accurately define the EAA content of USDA protein food ounce-equivalents, to develop a more accurate food exchange list, and to evaluate the EAA-9 protein quality framework as a tool for determining precise EAA-equivalent substitutions.

Psychometric Validation of the CLN2 Quality of Life Questionnaire in Participants with CLN2 Disease Treated with Cerliponase Alfa.

Objectives: This study evaluated the psychometric properties of the ceroid lipofuscinosis type 2 Quality of Life (CLN2 QoL) questionnaire.

Methods: Data from children with CLN2 disease aged 3-16 years receiving cerliponase alfa in the BMN 190-201 and BMN 190-202 clinical studies, collected via purposive sampling, were used to assess convergent and divergent validity, internal consistency and reliability. The clinically important difference (CID) was estimated with distribution- and anchor-based methods.

Telehealth access and experiences of older adults with HIV during the COVID-19 pandemic: Lessons for the future.

Background: Telehealth services are proposed to improve access and retention to care for people with HIV (PWH). Yet the rapid uptake of telehealth services during the COVID-19 pandemic created equity concerns, especially for already vulnerable populations. Older PWH may face a combination of barriers to telehealth but also stand to benefit given social isolation and the need for multimorbidity management.

Exploring concurrent validity of the CLN2 Clinical Rating Scale: Comparison to PedsQL using cerliponase alfa clinical trial data.

Background: The CLN2 Clinical Rating Scale evaluates disease progression in CLN2 disease, an ultra-rare, neurodegenerative disorder with late infantile onset. To validate the Clinical Rating Scale, a comparison with the Pediatric Quality of Life Inventory (PedsQL) was conducted utilising clinical trial data investigating cerliponase alfa use in CLN2 disease.

Methods: Linear regression and mixed effects models were used to investigate the relationship between the Clinical Rating Scale and PedsQL using open-label, single-arm, phase 1/2 (NCT01907087) and ongoing extension study (NCT02485899) data of 23 children with CLN2 disease treated with cerliponase alfa for ≥96 weeks.

Natural History of Neuronal Ceroid Lipofuscinosis Type 6, Late Infantile Disease.

Background: Mutations in the CLN6 gene cause late infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disease of childhood onset. Clinically, individuals present with progressive motor and cognitive regression, ataxia, and early death. The aim of this study is to establish natural history data of individuals with classic, late-infantile-onset (age less than five years) CLN6 disease.

Peripheral retinal finding on fluorescein angiography in neuronal ceroid lipofuscinosis type 2 (CLN2).

Classically, peripheral vascular changes in the retina in patients with neuronal ceroid lipofuscinosis type 2 (CLN2) are described as vascular attenuation seen in the late stages of disease on the Weill Connell Ophthalmic Severity Score (WCOSS) staging system. We describe isolated, mild, peripheral vasculitis with peripheral arteriolar dropout identified by fluorescein angiography in patients with a WCOSS grade of stage 2. We believe this vasculitis represents an early vasodegenerative phase of disease that leads to the vascular attenuation seen in later stages of the disease.

Developmental Skills and Neurorehabilitation for Children With Batten Disease: A Retrospective Chart Review of a Comprehensive Batten Clinic.

Background: Batten disease is a rare, progressive neurogenetic disorder composed of 13 genotypes that often presents in childhood. Children present with seizures, vision loss, and developmental regression. Neurorehabilitation services (i.

Safety and efficacy of cerliponase alfa in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease): an open-label extension study.

Background: Cerliponase alfa is a recombinant human tripeptidyl peptidase 1 (TPP1) enzyme replacement therapy for the treatment of neuronal ceroid lipofuscinosis type 2 (CLN2 disease), which is caused by mutations in the TPP1 gene. We aimed to determine the long-term safety and efficacy of intracerebroventricular cerliponase alfa in children with CLN2 disease.

Methods: This analysis includes cumulative data from a primary 48-week, single-arm, open-label, multicentre, dose-escalation study (NCT01907087) and the 240-week open-label extension with 6-month safety follow-up, conducted at five hospitals in Germany, Italy, the UK, and the USA.

Deep Brain Stimulation for the Management of AIFM1-Related Disabling Tremor: A Case Series.

The AIFM1 gene encodes a mitochondrial protein that acts as a flavin adenine dinucleotide-dependent nicotinamide adenine dinucleotide oxidase and apoptosis regulator. Monoallelic pathogenic AIFM1 variants result in a spectrum of X-linked neurological disorders, including Cowchock syndrome. Common features in Cowchock syndrome include a slowly progressive movement disorder, cerebellar ataxia, progressive sensorineural hearing loss, and sensory neuropathy.

La Crosse Virus Neuroinvasive Disease in Children: A Contemporary Analysis of Clinical/Neurobehavioral Outcomes and Predictors of Disease Severity.

Background: La Crosse virus (LACV) is the most common neuroinvasive arboviral infection in children in the United States. However, data regarding predictors of disease severity and neurologic outcome are limited. Additionally, long-term neurologic and neurobehavioral outcomes remain relatively sparse.

Inherited and de novo variants extend the etiology of -associated neurodevelopmental disorder.

Alterations in the gene have recently emerged as the cause of developmental delay with or without intellectual impairment or behavioral abnormalities (MIM # 619575). The 32 cases currently described in the literature have predominantly de novo alterations in and a wide spectrum of neurodevelopmental abnormalities. Here, we report four patients with novel pathogenic variants identified by research genome sequencing, clinical exome sequencing, and international matchmaking.

Biallelic variants in two siblings with pontocerebellar hypoplasia type 2D underscore the relevance of splice-disrupting synonymous variants in disease.

Noncoding and synonymous coding variants that exert their effects via alternative splicing are increasingly recognized as an important category of disease-causing variants. In this report, we describe two siblings who presented with hypotonia, profound developmental delays, and seizures. Brain magnetic resonance imaging (MRI) in the proband at 5 yr showed diffuse cerebral and cerebellar white matter volume loss.

Editorial commentary on "Gait phenotype in Batten disease: A marker of disease progression".

Batten disease, also known as neuronal ceroid lipofuscinosis, refers to a diverse group of 13 hereditary inborn errors of metabolism resulting in the abnormal accumulation of autofluorescent storage material in lysosomes leading to neurodegeneration, typically with associated intractable epilepsy, behavioral dysregulation, cognitive, motor, language and visual decline, as well as a shortened life expectancy [1]. Assessment of disease progression within this population is fraught with difficulty because individuals may have limited attention or cooperation affecting compliance with requested tasks, or have visual impairment reducing options for methods of assessment. Further, language and cognitive assessments have been designed to assess typically developing individuals based on specific age limits, which then fail to capture low developmental functioning once the mental age of the individual drops below the basal age of the assessment tool.

Utilizing telehealth to create a clinical model of care for patients with Batten disease and other rare diseases.

Unlabelled: The COVID-19 pandemic transformed the delivery of healthcare across the world. Telehealth has emerged as the primary method for providing healthcare early in the pandemic. Patient and healthcare provider views of the effectiveness of telehealth services are encouraging and support the long-term use of telehealth services in clinical practice.

Management of CLN1 Disease: International Clinical Consensus.

Background: CLN1 disease (neuronal ceroid lipofuscinosis type 1) is a rare, genetic, neurodegenerative lysosomal storage disorder caused by palmitoyl-protein thioesterase 1 (PPT1) enzyme deficiency. Clinical features include developmental delay, psychomotor regression, seizures, ataxia, movement disorders, visual impairment, and early death. In general, the later the age at symptom onset, the more protracted the disease course.

Risperidone or Aripiprazole Can Resolve Autism Core Signs and Symptoms in Young Children: Case Study.

Risperidone and aripiprazole are approved by the USA Food and Drug Administration for the treatment of irritability and aggression in children from the ages of 5 and 6 years, respectively. However, there are no approved medications for the treatment of autism spectrum disorder (ASD) core signs and symptoms. Nevertheless, early intervention is recognized as key to improving long-term outcomes.

Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients.

Background: CLN2 disease (Neuronal Ceroid Lipofuscinosis Type 2) is an ultra-rare, neurodegenerative lysosomal storage disease, caused by an enzyme deficiency of tripeptidyl peptidase 1 (TPP1). Lack of disease awareness and the non-specificity of presenting symptoms often leads to delayed diagnosis. These guidelines provide robust evidence-based, expert-agreed recommendations on the risks/benefits of disease-modifying treatments and the medical interventions used to manage this condition.

Cerliponase Alfa for the Treatment of Atypical Phenotypes of CLN2 Disease: A Retrospective Case Series.

Background: The classic phenotype of CLN2 disease (neuronal ceroid lipofuscinosis type 2) typically manifests between ages 2 and 4 years with a predictable clinical course marked by epilepsy, language developmental delay, and rapid psychomotor decline. Atypical phenotypes exhibit variable time of onset, symptomatology, and/or progression. Intracerebroventricular-administered cerliponase alfa (rhTPP1 enzyme) has been shown to stabilize motor and language function loss in patients with classic CLN2 disease, but its impact on individuals with atypical phenotypes has not been described.

Current knowledge of SLC6A1-related neurodevelopmental disorders.

Advances in gene discovery have identified genetic variants in the solute carrier family 6 member 1 gene as a monogenic cause of neurodevelopmental disorders, including epilepsy with myoclonic atonic seizures, autism spectrum disorder and intellectual disability. The solute carrier family 6 member 1 gene encodes for the GABA transporter protein type 1, which is responsible for the reuptake of the neurotransmitter GABA, the primary inhibitory neurotransmitter in the central nervous system, from the extracellular space. GABAergic inhibition is essential to counterbalance neuronal excitation, and when significantly disrupted, it negatively impacts brain development leading to developmental differences and seizures.

Pharmacological Intervention in Children with Autism Spectrum Disorder with Standard Supportive Therapies Significantly Improves Core Signs and Symptoms: A Single-Center, Retrospective Case Series.

Purpose: Autism spectrum disorder (ASD) is a debilitating neurodevelopmental disorder with high heterogeneity and no clear common cause. Several drugs, in particular risperidone and aripiprazole, are used to treat comorbid challenging behaviors in children with ASD. Treatment with risperidone and aripiprazole is currently recommended by the Food and Drug Administration (FDA) in the USA for children aged 5 and 6 years and older, respectively.

Clinical Pharmacokinetics and Pharmacodynamics of Cerliponase Alfa, Enzyme Replacement Therapy for CLN2 Disease by Intracerebroventricular Administration.

Cerliponase alfa is recombinant human tripeptidyl peptidase 1 (TPP1) delivered by i.c.v.

Intracerebroventricular Cerliponase Alfa for Neuronal Ceroid Lipofuscinosis Type 2 Disease: Clinical Practice Considerations From US Clinics.

Background: Neuronal ceroid lipofuscinosis type 2 or CLN2 disease is a rare, autosomal recessive, neurodegenerative lysosomal storage disorder caused by tripeptidyl peptidase 1 deficiency. Cerliponase alfa, a recombinant human tripeptidyl peptidase 1 enzyme, is the first and only approved treatment for CLN2 disease and the first approved enzyme replacement therapy administered via intracerebroventricular infusion.

Methods: A meeting of health care professionals from US institutions with experience in cerliponase alfa treatment of children with CLN2 disease was held in November 2018.

Batten disease and perioperative complications: a retrospective descriptive study.

Purpose: Batten disease or neuronal ceroid lipofuscinosis is the most prevalent neurodegenerative disorder of childhood. Previously reported perioperative complications in children with Batten disease have come mainly from single case reports. The primary aim of the current study was to investigate perioperative complications of patients with Batten disease in the largest cohort known to date.

Language Regression in an Atypical SLC6A1 Mutation.

Recent technological advances in exome sequencing or targeted gene sequencing with epilepsy panels have allowed clinicians to better understand the pathogenesis and clinical presentation of children with epilepsy. We present a child with a SLC6A1 mutation with language delay and autistic spectrum disorder and remind the reader that the identification of specific mutations in these conditions increase the likelihood of identification of potential therapeutic targets.