Developmental delay can precede neurologic regression in early onset metachromatic leukodystrophy.

Objective: Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disorder. Emerging therapies are most effective in the presymptomatic phase, and thus defining this window is critical. We hypothesize that early development delay may precede developmental plateau.

Long-term neurodevelopmental outcomes of hematopoietic stem cell transplantation for late-infantile Krabbe disease.

Krabbe disease is a rare neurodegenerative disorder caused by a deficiency in galactocerebrosidase. The only effective treatment is hematopoietic stem cell transplantation (HSCT). Approximately 85% of Krabbe disease cases are the infantile subtypes, among which ∼20% are late infantile.

Spontaneous Third Ventriculostomy in Krabbe Disease.

Introduction: Spontaneous third ventriculostomies have been reported in relation to obstructive hydrocephalus and increased intracranial pressure and are most commonly seen as disruption of the floor of the third ventricle. Hydrocephalus has been reported in patients with Krabbe disease; however, it is clinically difficult to monitor for hydrocephalus in patients with Krabbe disease as symptoms of increased intracranial pressure may overlap with symptoms of Krabbe disease. We describe a case series of spontaneous third ventriculostomy and hydrocephalus, likely in response to increased intracranial pressure, in patients with infantile Krabbe disease.

General anesthesia safety in progressive leukodystrophies: A retrospective study of patients with Krabbe disease and metachromatic leukodystrophy.

Background: Krabbe disease and metachromatic leukodystrophy are leukodystrophies characterized by neurologic degeneration and early death. Patients often require general anesthesia for diagnostic and therapeutic interventions.

Methods: A retrospective review of medical records was conducted for patients with Krabbe disease and metachromatic leukodystrophy receiving general anesthesia at a large children's hospital between 2012 and 2017.

Early progression of Krabbe disease in patients with symptom onset between 0 and 5 months.

Background: Krabbe disease is a rare neurological disorder caused by a deficiency in the lysosomal enzyme, β-galactocerebrosidase, resulting in demyelination of the central and peripheral nervous systems. If left without treatment, Krabbe disease results in progressive neurodegeneration with reduced quality of life and early death. The purpose of this prospective study was to describe the natural progression of early onset Krabbe disease in a large cohort of patients.

Development of a newborn screening tool based on bivariate normal limits: using psychosine and galactocerebrosidase determination on dried blood spots to predict Krabbe disease.

Purpose: Newborn screening for Krabbe disease (KD) originated in New York State in 2006 but has proven to have a high false positive rate and low positive predictive value. To improve accuracy of presymptomatic prediction, we propose a screening tool based on two biomarkers, psychosine and galactocerebrosidase enzyme activity (GalC).

Methods: We developed the tool using measures from dried blood spots of 166 normal newborns and tested it on dried blood spot measures from 15 newborns who later developed KD, 8 newborns identified as "high risk" by the New York screening protocol but were disease-free at follow-up, and 3 symptomatic children with onset before 4 years of age.

A prospective natural history study of Krabbe disease in a patient cohort with onset between 6 months and 3 years of life.

Background: Krabbe disease is a rare neurodegenerative disorder caused by a deficiency in the lysosomal enzyme galactocerebrosidase. Patients with Krabbe disease present with a variable disease course depending on their age of onset. The purpose of this prospective cohort study was to characterize the natural progression of Krabbe disease in a large group of patients with disease onset between 6 and 36 months of life who were evaluated with a standardized protocol.

The Emergence of Effortful Control in Young Boys With Fragile X Syndrome.

Effortful control, or the ability to suppress a dominant response to perform a subdominant response, is an early-emerging temperament trait that is linked with positive social-emotional development. Fragile X syndrome (FXS) is a single-gene disorder characterized by hallmark regulatory impairments, suggesting diminished effortful control. This study compared the development of effortful control in preschool boys with FXS ( n = 97) and typical development ( n = 32).

Developmental outcomes of cord blood transplantation for Krabbe disease: A 15-year study.

Objective: To describe long-term outcomes of children with early-infantile Krabbe disease who underwent hematopoietic stem cell transplantation (HSCT) in the first 7 weeks of life.

Methods: In this prospective longitudinal study, evaluations performed at baseline and follow-up included brain imaging, neurodiagnostic tests, and neurobehavioral evaluations.

Results: Of the 18 patients in this study (11 girls, 7 boys; mean follow-up 9.

Early disease progression of Hurler syndrome.

Background: Newborn screening for mucopolysaccharidosis type I (MPS I) shows promise to improve outcomes by facilitating early diagnosis and treatment. However, diagnostic tests for MPS I are of limited value in predicting whether a child will develop severe central nervous system disease associated with Hurler syndrome, or minimal or no central nervous system involvement associated with the attenuated phenotypes (Hurler-Scheie and Scheie syndromes). Given that the optimal treatment differs between Hurler syndrome and the attenuated MPS I phenotypes, the absence of a reliable prognostic biomarker complicates clinical decision making for infants diagnosed through newborn screening.

Clinical management of Krabbe disease.

Krabbe disease (KD) is a rare neurodegenerative disorder caused by mutations in the gene encoding the galactocerebrosidase enzyme. The early- and late-infantile subtypes, which are the most common forms of the disease, are rapidly progressive and lead to early death, whereas the later-onset types are clinically heterogeneous. The only disease-modifying treatment currently available is hematopoietic stem cell transplantation, which is effective only when performed early in the course of the disease.

Thickening of the cauda equina roots: a common finding in Krabbe disease.

Objectives: Evaluation of Krabbe disease burden and eligibility for hematopoietic stem cell transplantation are often based on neuroimaging findings using the modified Loes scoring system, which encompasses central but not peripheral nervous system changes. We show that quantitative evaluation of thickened cauda equina nerve roots may improve the evaluation of Krabbe disease and therapeutic guidance.

Methods: Lumbar spine MRI scans of patients obtained between March 2013 and September 2013 were retrospectively evaluated and compared to those of controls.

Midbrain morphology reflects extent of brain damage in Krabbe disease.

Introduction: To study the relationships between midbrain morphology, Loes score, gross motor function, and cognitive function in infantile Krabbe disease.

Methods: Magnetic resonance imaging (MRI) scans were evaluated by two neuroradiologists blinded to clinical status and neurodevelopmental function of children with early or late infantile Krabbe disease. A simplified qualitative 3-point scoring system based on midbrain morphology on midsagittal MRI was used.

Long-term functional outcomes of children with hurler syndrome treated with unrelated umbilical cord blood transplantation.

Objectives: Hurler syndrome is characterized by progressive multisystem deterioration leading to early death in childhood. This prospective study evaluated the long-term outcomes of patients with Hurler syndrome who underwent umbilical cord blood transplantation from unrelated donors.

Study Design: Only patients with Hurler syndrome who underwent umbilical cord blood transplantation between December 1995 and March 2006 (n = 25) and who were followed for at least 5 years (n = 19) were included in the analysis.

Early treatment is associated with improved cognition in Hurler syndrome.

Objective: Hurler syndrome is the most clinically severe form of an autosomal recessive lysosomal disorder characterized by the deficiency of α-L-iduronidase. The resulting accumulation of glycosaminoglycans causes progressive multisystem deterioration, resulting in death in childhood. Umbilical cord blood transplantation from unrelated donors has been previously shown to improve neurological outcomes of children <2 years of age and prolong life.

Natural history of Sanfilippo syndrome type A.

Objective: To describe the natural history of Sanfilippo syndrome type A.

Methods: We performed a retrospective review of 46 children (21 boys, 25 girls) with Sanfilippo syndrome type A evaluated between January 2000 and April 2013. Assessments included neurodevelopmental evaluations, audiologic testing, and assessment of growth, adaptive behavior, cognitive behavior, motor function, and speech/language skills.

Hyporesponsiveness to social and nonsocial sensory stimuli in children with autism, children with developmental delays, and typically developing children.

This cross-sectional study seeks to (a) describe developmental correlates of sensory hyporesponsiveness to social and nonsocial stimuli, (b) determine whether hyporesponsiveness is generalized across contexts in children with autism relative to controls, and (c) test the associations between hyporesponsiveness and social communication outcomes. Three groups of children ages 11-105 months (N = 178; autism = 63, developmental delay = 47, typical development = 68) are given developmental and sensory measures including a behavioral orienting task (the Sensory Processing Assessment). Lab measures are significantly correlated with parental reports of sensory hyporesponsiveness.

Neurodevelopmental outcomes of umbilical cord blood transplantation in metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD) is an inherited demyelinating disease that causes progressive neurologic deterioration, leading to severe motor disability, developmental regression, seizures, blindness, deafness, and death. The disease presents as a late-infantile, juvenile, or adult form. Hematopoietic stem cell transplantation has been shown to slow disease progression.

Trajectories of early brain volume development in fragile X syndrome and autism.

Objective: To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared with a comparison group (controls) and a group with idiopathic autism.

Method: The study included 53 boys 18 to 42 months of age with FXS, 68 boys with idiopathic autism (autism spectrum disorder), and a comparison group of 50 typically developing and developmentally delayed controls. Structural brain volumes were examined using magnetic resonance imaging across two time points, at 2 to 3 and again at 4 to 5 years of age, and total brain volumes and regional (lobar) tissue volumes were examined.

Differential associations between sensory response patterns and language, social, and communication measures in children with autism or other developmental disabilities.

Purpose: To examine patterns of sensory responsiveness (i.e., hyperresponsiveness, hyporesponsiveness, and sensory seeking) as factors that may account for variability in social-communicative symptoms of autism and variability in language, social, and communication skill development in children with autism or other developmental disabilities (DDs).

To what extent do joint attention, imitation, and object play behaviors in infancy predict later communication and intellectual functioning in ASD?

The extent to which early social communication behaviors predict later communication and intellectual outcomes was investigated via retrospective video analysis. Joint attention, imitation, and complex object play behaviors were coded from edited home videos featuring scenes of 29 children with ASD at 9-12 and/or 15-18 months. A quantitative interval recording of behavior and a qualitative rating of the developmental level were applied.

Early brain overgrowth in autism associated with an increase in cortical surface area before age 2 years.

Context: Brain enlargement has been observed in 2-year-old children with autism, but the underlying mechanisms are unknown.

Objective: To investigate early growth trajectories in brain volume and cortical thickness.

Design: Longitudinal magnetic resonance imaging study.

Early clinical markers of central nervous system involvement in mucopolysaccharidosis type II.

Objective: To identify early clinical markers of neurologic involvement in mucopolysaccharidosis type II.

Study Design: A retrospective review of neurobehavioral standardized assessments of patients with mucopolysaccharidosis type II evaluated at the Program for Neurodevelopmental Function in Rare Disorders was completed. Patients were grouped based on the presence or absence of central nervous system (CNS) involvement at the most recent evaluation.

Natural progression of neurological disease in mucopolysaccharidosis type II.

Objective: Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder characterized by insufficiency of the iduronate-2-sulfatase enzyme, which results in excess heparan and dermatan sulfates within the lysosomes of various tissues and organs, including the central nervous system. The purpose of this study was to investigate the natural progression of neurologic disease in a large cohort of patients evaluated with standardized testing at a single institution.

Methods: During the period of December 2002 to October 2010, patients with MPS II were referred to the Program for Neurodevelopmental Function in Rare Disorders.