Alterations in the SLC6A9 gene result in a dysfunction of glycine transport and cause Glycine transporter 1 encephalopathy (GLYT1 encephalopathy, also known as glycine encephalopathy with normal serum glycine).
At birth, newborns with GLYT1 encephalopathy manifest breathing problems, muscles with a very low tone (later, stiffness of the legs and arms is observed), absent neonatal reflexes, startles caused by sudden loud noises or physical contact, malformed limbs with fixed contractures of the arms and legs (called arthrogryposis multiplex congenita), and increased glycine levels in cerebrospinal fluid. Brain magnetic resonance imaging and electroencephalogram may show alterations. Physical appearance of patients is special, with non-typical shapes of head, face, ears, eyes and nose. Most patients die in the first months of life, and those who survive present a severe developmental delay. During pregnancy, fetal abnormalities can be detected by ultrasound examination.
The prevalence of GLYT1 encephalopathy is unknown. So far, only ten affected individuals from five unrelated families have been described.
The diagnosis of GLYT1 encephalopathy is confirmed through genetic diagnostic techniques demonstrating two mutations in the SCL6A9 gene. The inheritance pattern of the disease is autosomal recessive, and the risk of recurrence in couples with a previous affected child is high (25%). There is the possibility of prenatal and preimplantation genetic diagnosis.
SLC6A9