atypical glycine encephalopathy

Atypical glycine encephalopathy is a neurological disorder that affects how the brain processes the amino acid glycine. It results from changes in the SLC6A9 gene, which encodes a transporter that normally helps move excess glycine out of nerve cells. Unlike the classic neonatal form of glycine encephalopathy, this atypical type can present later in infancy, childhood, or beyond and may follow a more variable clinical course. The condition is extremely uncommon, affecting fewer than one in a million people worldwide. Both males and females can be affected.

Because glycine acts as a neurotransmitter, most signs of atypical glycine encephalopathy involve cognitive and other neurological functions. Vision problems are common, and optic atrophy, a gradual thinning of the optic nerve, is reported in many affected individuals. Some children are born with or later develop a smaller than expected head size, a feature called microcephaly, although this occurs only in a subset of cases. Age at onset and symptom severity differ from person to person, and not all individuals experience all features. Severity and symptoms vary widely between individuals, and the range can include relatively mild challenges to profound impairment.

Atypical glycine encephalopathy is caused by pathogenic variants in the SLC6A9 gene. The protein produced by this gene, glycine transporter 1, helps regulate glycine levels in the brain and other tissues. When the transporter does not work properly, glycine can accumulate around neurons and disrupt normal signaling, leading to the clinical problems seen in the disorder. The condition is inherited in an autosomal recessive pattern, meaning a child must receive one altered copy of SLC6A9 from each parent to be affected. This situation is more likely when parents share a common ancestor, because they have a higher chance of carrying the same rare genetic change. Carrier parents have a 25 percent chance with each pregnancy of having an affected child. Genetic counseling can help families understand these risks and discuss options for future family planning.

Currently, management focuses on supportive care and symptom management. Treatment is tailored to the individual and often involves a multidisciplinary team that may include neurologists, ophthalmologists, physical and occupational therapists, and nutrition specialists. Regular ophthalmologic evaluations help monitor vision because optic atrophy can progress over time. Developmental and educational services support cognitive and motor skills, and seizure management or other neurological therapies are introduced if needed. Genetic counseling is recommended for affected individuals and their families to discuss inheritance, recurrence risk, and available resources. Patients should discuss treatment options with their healthcare team to determine which therapies may be appropriate for their specific situation.

Outcomes depend on many factors, including the severity of neurological involvement, the age at which symptoms begin, and access to specialized care. Some individuals have significant developmental challenges, while others achieve greater degrees of independence. Because so few cases have been described, long-term data are limited, and understanding of the natural history continues to evolve. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with expert centers and patient support communities, and participation in disease registries can advance research and provide additional guidance.

Clinical trials are underway exploring new treatment approaches for atypical glycine encephalopathy. Individuals interested in participating can search ClinicalTrials.gov or consult their care team about eligibility.