congenital disorder of deglycosylation 1

Congenital disorder of deglycosylation 1 is a rare multisystem condition caused by mutations in the NGLY1 gene. It primarily affects children, with developmental challenges and other neurological issues manifesting early in life. The condition is inherited in an autosomal recessive manner and is very rare, affecting fewer than 1 in 1 million people. Advances in supportive care have improved outcomes, although the course remains variable.

Individuals with congenital disorder of deglycosylation 1 typically present with a range of neurological and systemic symptoms. Characteristic features include persistent hypotonia, global developmental delay, and intellectual disability. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, followed by variable stabilization or further decline. In addition, affected children often exhibit abnormal involuntary movements, seizures, poor tear production, and difficulties with oral-pharyngeal swallowing. Other clinical features such as microcephaly, distinctive excretion patterns in urine, and liver abnormalities contribute to the complex multisystem presentation. Not all individuals experience all features, and severity varies considerably.

This condition is caused by mutations in the NGLY1 gene, which encodes an enzyme critical for the deglycosylation process. It follows an autosomal recessive inheritance pattern, meaning that an affected individual inherits two copies of the mutated gene, one from each parent. The condition is more common when parents share a common ancestor, increasing the likelihood that both carry the same rare genetic variant. Families are encouraged to seek genetic counseling to better understand recurrence risks and to discuss family planning options.

Currently, management focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically for congenital disorder of deglycosylation 1. Treatment is tailored to each individual and typically involves a multidisciplinary team approach, including regular surveillance and monitoring to address both neurological and systemic issues. Supportive therapies may include physical and occupational therapy, and genetic counseling is recommended to help families understand the condition and explore management strategies. Patients should discuss treatment options with their healthcare team to determine which therapies are most appropriate for their situation.

Congenital disorder of deglycosylation 1 is a lifelong neurodevelopmental condition characterized by an initial regression followed by a period of relative stabilization, with some individuals experiencing later motor decline. Outcomes vary widely depending on symptom severity, age at diagnosis, and access to specialized care. With current standards of care, many individuals experience improvements in quality of life, and modern management strategies continue to evolve. Outcomes described in medical literature continue to evolve as standards of care improve. Families are encouraged to connect with genetic counselors and relevant specialists to receive guidance on long-term planning and support.

Clinical trials are underway exploring new treatment approaches, and individuals interested in experimental therapies can search ClinicalTrials.gov or consult their care team about eligibility.