NGLY1 deficiency is a rare disorder that can affect multiple body systems. Affected individuals may have failure to reach developmental milestones, intellectual disability, movement disorders, seizures, liver disease, and an inability to produce tears when crying (alcryma) or rarely produce tears. The specific symptoms and severity of the disorder can vary significantly among affected individuals. Additional symptoms may develop in some children. NGLY1 deficiency is caused by a disease-causing variant (mutation) in the NGLY1 gene. This variant is inherited in an autosomal recessive pattern. As of April 2021, fewer than 100 people have been identified with NGLY1 deficiency. Affected infants often have reduced muscle tone (hypotonia), in which the child is described as being excessively “floppy”. About half of all infants are born with low birth weight and, despite a normal appetite, many infants will fail to gain weight or grow for their age and sex (growth failure). Some infants have difficulty swallowing and are at risk of food or liquids going down the wrong tube and ending up in the lungs (aspiration). Constipation may also occur. In some infants, head circumference, which is normal at birth, may be smaller than expected with age (acquired microcephaly). NGLY1 deficiency syndrome is caused by mutations in the NGLY1 gene, which is located on the short arm of chromosome 3 at 3p24.2. Genes provide instructions for making proteins that play an important role in many body functions. When a mutation occurs in a gene, the protein product may be defective, ineffective, absent, or overproduced. Depending on the function of the specific protein, this can affect many organs in the body, including the brain.