NGLY1 Deficiency: A Prospective Natural History Study

Study Overview
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Brief Summary
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NGLY1 deficiency is a rare genetic disorder that is characterized by: global developmental delay and/or intellectual disability, hypo- or alacrima, transient elevation of transaminases, and a hyperkinetic movement disorder. Significant phenotypic variability has been observed in the small number of affected individuals described in the medical literature. The purpose of this study is to describe the natural history of NGLY1 deficiency in a prospective, detailed, and highly uniform manner. Study participants will be closely monitored over the course of five years in order to: understand the clinical spectrum and progression of NGLY1 deficiency using standardized clinical and neurodevelopmental assessments identify clinical and biomarker endpoints for use in therapeutic trials, and identify genotype-phenotype correlations Close clinical follow-up will allow for generation of a rich dataset and detailed understanding of the natural history of NGLY1 deficiency.

Official Title
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NGLY1 Deficiency: A Prospective Natural History Study

Conditions
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Genetic Syndrome

Intervention / Treatment
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* Other: Neurodevelopmental Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parent(s)/legal representative and/or participant must be willing and able to give informed consent/assent for participation in the study Males or females of any age Suspected or confirmed diagnosis of NGLY1 deficiency with genetic variants in both NGLY1 alleles and consistent clinical characteristics Participant and caregiver must be willing to provide clinical data, participate in standardized assessments, and provide biological samples (if living in the United States) Willingness to travel to Palo Alto, CA is favored, but not required Exclusion Criteria: The presence of a second, confirmed disorder, genetic or otherwise, affecting neurodevelopment or with other overlapping symptoms of NGLY1 deficiency
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Neurodevelopmental Assessment|Developmental assessment at baseline and longitudinally as measured by age and ability-appropriate scales, including: the Mullen Scales of Early Learning, the Peabody Scales of Motor Development, the Vineland 3, and Beery Visual Motor Integration|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detailed phenotyping of the clinical course of NGLY1 deficiency over time | Conducted in patients with NGLY1 deficiency: detailed standardized general, neurologic, dysmorphologic, and ophthalmologic evaluations; clinical laboratory studies; electroencephalogram; nerve conduction studies; quantitative studies of autonomic function; scoring of movement disorder and NGLY1 deficiency symptom scales; and a timed 10-meter walk test. As much information as available will also be collected from existing medical records including clinical evaluations, imaging studies and neuropsychological and motor function evaluations. | 5 years | 
| Neurodevelopmental profile of NGLY1 deficiency as measured using Mullen Scales of Early Learning | Developmental assessment at baseline and longitudinally, if age and ability-appropriate. | 5 years | 
| Neurodevelopmental profile of NGLY1 deficiency as measured using Bruininks-Oseretsky Test of Motor Proficiency, Second Edition | Developmental assessment at baseline and longitudinally, if age and ability-appropriate. | 5 years | 
| Neurodevelopmental profile of NGLY1 deficiency as measured using the Peabody Scales of Motor Development | Developmental assessment at baseline and longitudinally, if age and ability-appropriate. | 5 years | 
| Neurodevelopmental profile of NGLY1 deficiency as measured using the Differential Ability Scales II | Developmental assessment at baseline and longitudinally, if age and ability-appropriate. | 5 years | 
| Neurodevelopmental profile of NGLY1 deficiency as measured using the Beery Visual Motor Integration developmental test | Developmental assessment at baseline and longitudinally, if age and ability-appropriate. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL) | Quality of life will be evaluated at baseline and longitudinally. | 5 years | 
| Caregiver quality of life as measured through the 36 Item Short Form Survey (SF36) | Quality of life will be evaluated at baseline and longitudinally. Caregivers will complete the survey but will not be enrolled in the study. | 5 years | 
| Biomarkers for NGLY1 deficiency identified during the course of the study | Longitudinal collection and monitoring of laboratory studies and clinical presentation as measured through standardized and quantitative assessments may identify biomarkers for NGLY1 deficiency. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NGLY1 Deficiency