SNP Shot: Genomic Insights

Nonketotic hyperglycinemia (NKH) is a condition characterized by an excess of glycine, a molecule, in the body (hyperglycinemia). This buildup of glycine is especially prominent in the brain and other tissues, leading to significant neurological problems in affected individuals.

There are two main forms of NKH: a severe form and an attenuated (milder) form. Both typically manifest shortly after birth, although some cases may present within the first few months. The attenuated form can also present later in infancy. The severity of symptoms differentiates the two forms, with severe NKH being the more prevalent. Infants with severe NKH exhibit extreme lethargy that progressively worsens, potentially leading to coma. They may also experience hypotonia (weak muscle tone) and life-threatening respiratory issues within the initial days or weeks. Survivors often develop feeding difficulties, spasticity (abnormal muscle stiffness), profound intellectual disability, and intractable seizures. Most fail to achieve typical developmental milestones like bottle feeding, sitting, or grasping, and may even lose previously acquired skills.

The attenuated form of NKH presents with similar symptoms, but they are less severe than those seen in the severe form. Children with attenuated NKH often reach some developmental milestones, though the extent of their abilities varies greatly. Despite developmental delays, many learn to walk and interact with others, often using sign language. Seizures can occur, but they are generally mild and treatable. Other potential features include spasticity, chorea (involuntary jerking movements), and hyperactivity.

Brain abnormalities, detectable through MRI, can also be present in individuals with NKH. For instance, children with severe NKH may have a smaller-than-average corpus callosum, the tissue connecting the brain's two hemispheres.

Inheritance:

NKH follows an autosomal recessive inheritance pattern. This means that both copies of the responsible gene within each cell must carry mutations for the condition to develop. Typically, the parents of an affected individual each carry one copy of the mutated gene without displaying symptoms themselves. In rare instances, a de novo mutation, occurring during the formation of reproductive cells or in early embryonic development, may be responsible.