NGLY1 Natural History

NCT06122766 | Completed

• 1 other identifier: H-49928
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

N-glycanase 1 (NGLY1) Deficiency (OMIM #615273) is an ultra-rare, autosomal recessive disorder caused by loss of function variants in NGLY1 gene. The multisystemic disorder is characterized by five key features: (1) global developmental delay and/or intellectual disability, (2) a (primarily) hyperkinetic movement disorder (3) transient elevation of liver transaminases (4) (hypo)- alacrima and (5) peripheral neuropathy. The condition was first reported in 2012 and thus comprehensive characterization of the disease, especially its unique movement disorder, continues to be described. The hyperkinetic movement disorder in NGLY1 Deficiency is highly complex and has been qualitatively described to include choreiform, athetoid, dystonic, myoclonic, action tremor, and dysmetric movements. These descriptors apply to both lower and upper limb movement in individuals with NGLY1 Deficiency. Preliminary results indicate that NGLY1 Deficiency is associated with a myriad of movement control problems and range from being unable to perform certain arm movements or walk to behaviors that appear quite similar to age-matched neurotypical individuals. Preliminary results suggest that when reaching for objects, arm motion patterns tend to display unusual joint and hand trajectories, relative to neurotypical individuals, thereby decreasing their effectiveness/efficiency. During gait, range of joint motion, particularly at the knee, was often significantly reduced combined with evidence of leg movement asymmetry. Additionally, preliminary results indicate that there is low frequency tremor, particularly in the upper limbs, that tends to decline during arm acceleration. These preliminary findings, if confirmed in a larger sample, provide entryways to the understanding of how NGLY1 Deficiency impacts movement control and thereby may serve both as diagnostic and therapeutic endpoints for physicians and therapists. The purpose of this natural history study in NGLY1 Deficiency is to collect longitudinal measurements of movement concurrently with clinical and biomarker measures to aid in the development in end points for future therapeutic trials.

Conditions

NGLY1 Deficiency

Outcome Measures

Primary Outcomes (1)

• To characterize movement and gait disorder

  in a larger cohort of NGLY1 Deficiency subjects

  24 months

Secondary Outcomes (2)

• To determine the progression of movement disorder parameters

  24 months

• To describe associations between movement disorder parameters with relevant clinical measures

  24 months

Study Arms (1)

N-glycanase 1 (NGLY1) Deficiency

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

N-glycanase 1 (NGLY1) Deficiency (OMIM #615273) is an ultra-rare, autosomal recessive disorder caused by loss of function variants in NGLY1 gene. The multisystemic disorder is characterized by five key features: (1) global developmental delay and/or intellectual disability, (2) a (primarily) hyperkinetic movement disorder (3) transient elevation of liver transaminases (4) (hypo)- alacrima and (5) peripheral neuropathy.

You may qualify if:

• \- Individuals aged 2 to 25 years with a confirmed molecular diagnosis of NGLY1 Deficiency.

You may not qualify if:

• \- Prior or current participation in a therapeutic trial for NGLY1 Deficiency (note that neither the plan for future participation in an interventional trial nor participation in previous pilot study preclude entering this trial).

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Grace Science Foundation: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Plasma GNA samples will be collected as a secondary endpoint. The samples may be stored indefinitely after the end of the study to achieve study objectives. Additionally, with subjects' consent, samples may be used for further research by the sponsor or others such as universities or other companies to contribute to the understanding of NGLY1 or other diseases, the development of related or new treatments, or research methods.

MeSH Terms

Conditions

NGLY1 deficiency

Study Officials

• Bernhard Suter, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 2, 2023
• First Posted: November 8, 2023
• Study Start: February 27, 2023
• Primary Completion: October 24, 2024
• Study Completion: October 24, 2024
• Last Updated: April 11, 2025

Record last verified: 2024-12

Locations

US (1)