NGLY1 Deficiency: A Prospective Natural History Study

Stanford University29 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Genetic Syndrome

Interventions

Neurodevelopmental AssessmentOTHER

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

Sex: ALL

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 5 years

Neurodevelopmental profile of NGLY1 deficiency as measured using Mullen Scales of Early Learning