NGLY1 Deficiency: A Prospective Natural History Study

NCT03834987 | Terminated DMC

• 1 other identifier: IRB-47335
• Study Type: observational
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Genetic Syndrome

Keywords

NGLY1 Deficiency

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (3)

• Participant quality of life as measured through the Pediatric Quality of Life Inventory (PedsQL)

  5 years

• Caregiver quality of life as measured through the 36 Item Short Form Survey (SF36)

  5 years

• Biomarkers for NGLY1 deficiency identified during the course of the study

  5 years

Interventions

Neurodevelopmental Assessment OTHER

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals of any age with NGLY1 deficiency.

You may qualify if:

• 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

You may not qualify if:

• The presence of a second, confirmed disorder, genetic or otherwise, affecting neurodevelopment or with other overlapping symptoms of NGLY1 deficiency

Sponsors & Collaborators

• Stanford University: lead
• Grace Science Foundation: collaborator

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

Related Publications (2)

• Levy RJ, Frater CH, Gallentine WB, Phillips JM, Ruzhnikov MR. Delineating the epilepsy phenotype of NGLY1 deficiency. J Inherit Metab Dis. 2022 May;45(3):571-583. doi: 10.1002/jimd.12494. Epub 2022 Mar 11.

  PMID: 35243670 RESULT

• Frater CH, Ruzhnikov MRZ, Beres S, Alcorn D, Shue A, Levy RJ. Ocular features of NGLY1 deficiency from a prospective longitudinal cohort. J AAPOS. 2024 Jun;28(3):103925. doi: 10.1016/j.jaapos.2024.103925. Epub 2024 Apr 30.

  PMID: 38697387 DERIVED

Related Links

• Grace Science Foundation
• Neurogenomics at Stanford

Biospecimen

Retention: SAMPLES WITH DNA

Urine and blood samples.

MeSH Terms

Conditions

Genetic Diseases, Inborn; NGLY1 deficiency

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Maura Ruzhnikov, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: January 23, 2019
• First Posted: February 8, 2019
• Study Start: February 1, 2019
• Primary Completion: November 19, 2021
• Study Completion: November 19, 2021
• Last Updated: June 8, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)