Also known as:
- Glycine Encephalopathy
Nonketotic Hyperglycinemia (NKH) is an inherited condition in which the body is unable to breakdown and process some of the building blocks of protein (amino acids). It is considered an amino acid condition because it can lead to high levels of the amino acidglycine in the body. There are several forms of NKH, which differ in regards to disease severity and age of onset. The symptoms and long term outcome of each form vary widely. In some forms of NKH, detecting the condition early and beginning proper treatment may help prevent or delay some of the severe health outcomes associated with the condition. It is important to remember that every child diagnosed with NKH is affected differently.
Your baby’s doctor may ask you if your baby is showing any of the signs of NKH (see Early Signs below). If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment.
If your baby’s newborn screening result for Nonketotic hyperglycinemia (NKH) was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your child to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. An out-of-range result may occur because the initial blood sample was too small or the test was performed too early. However, as a few babies do have the condition, it is very important that you go to your follow-up appointment for a confirmatory test. Because the harmful effects of untreated NKH can occur soon after birth, follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition.
Follow-up testing will involve checking your baby’s urine, blood, and cerebrospinal fluid (the fluid that bathes the brain and spinal cord) samples for signs of NKH. Harmful amounts of certain substances build up in the body when a child has an amino acid condition, so measuring the amounts of these substances in your baby’s body can help doctors determine if your baby has a condition. High amounts of glycine in the blood, urine, and cerebrospinal fluid might indicate that your baby has NKH. Your baby’s doctor may also want to confirm the diagnosis with clinical genetic testing.
About Nonketotic hyperglycinemia
Signs of Nonketotic hyperglycinemia (NKH) can begin any time from infancy to adulthood and include:
- Sleeping longer or more often
- Weak muscle tone (also known as hypotonia)
- Wandering eye movements
- Abnormal jerky movements
- Difficulty feeding
- Difficulty breathing
- Developmental delay
The severity and age of onset of nonketotic hyperglycinemia (NKH) differs depending on the form. Babies with neonatal NKH, the most common and severe form, usually develop signs and symptoms in the first hours or days of life.
In the infantile form of NKH, babies appear healthy with normal development early in life. However, they typically develop seizures and various degrees of intellectual disability around six months of age.
Individuals with less common forms of NKH may develop symptoms later in childhood/adulthood (later onset form) or only display certain symptoms during times of stress or illness (mild-episodic form). If your baby shows any of these signs, be sure to contact your baby’s health care provider immediately.
Supplements and Medications
There is no cure for nonketotic hyperglycinemia (NKH). Sodium Benzoate and dextromethorphan are the prescribed treatments to help your baby’s body get rid of excess glycine and reduce seizures and symptoms of severe nonketotic hyperglycinemia (NKH). However, your baby’s doctor may recommend anti-epileptic drugs to reduce seizures also. Not all children with (NKH) respond to treatment, while others have great results.
Babies with NKH typically have varying degrees of developmental delay and intellectual disability. Occupational, physical and speech therapies are indicated to help your child reach his or her full potential.
It is possible that up to 30% of babies with the severe neonatal form of nonketotic hyperglycinemia (NKH) will pass away shortly after birth. Those that survive generally have severe seizures and profound intellectual disability.
Even with treatment, children with less severe forms of the condition generally experience varying degrees of intellectual disability, seizures and a variety of other health problems that primarily affect the central nervous system (brain and spinal cord).
When we eat food, enzymes help to break it down. Some enzymes break down proteins into their building blocks, called amino acids. Other enzymes break down these amino acids. In Nonketotic hyperglycinemia (NKH), the enzymes involved in breaking down the amino acid glycine are not working correctly.
NKH may affect the glycine cleavage enzyme (GCS). Individuals with NKH either do not make enough or make non-working copies of the GCS enzyme. If this enzyme is not working correctly, then the body cannot break down glycine. This causes high levels of glycine to build up in the blood, resulting in the signs and symptoms of NKH.
NKH is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for NKH, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with NKH is rare, when both parents are carriers, they can have more than one child with the condition. Learn more about autosomal recessive inheritance.
Support for Nonketotic hyperglycinemia
Support groups can help connect families who have a child or other family member affected with NKH with a supportive community of people who have experience and expertise in living with the condition. These organizations offer resources for families, affected individuals, health care providers, and advocates.
- NKH International Family Network - Support & family networking.
- Hope for NKH – fundraising for research & awareness
- NKH Crusaders - fundraising for research & awareness
- National Organization for Rare Diseases (NORD)
- Children Living with Inherited Metabolic Diseases (CLIMB)
Work with your baby’s health care provider to determine the next steps for your baby’s care. Your baby’s doctor may help you coordinate care with a physician that specializes in metabolism, a dietician who can help plan your child’s specialized diet, and other medical resources in your community. Some children with NKH have developmental delays. If you think that your baby is not meeting his or her developmental milestones, ask your baby’s doctor about the next steps in accessing a developmental evaluation and care.
Because NKH is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for NKH, and understand what this diagnosis means for other family members and future pregnancies. Speak with your baby’s doctor about getting a referral. The Clinic Services Search Engine offered by the National Coordinating Center for the Regional Genetic and Newborn Screening Service Collaboratives and the Find a Genetic Counselor tool on the National Society of Genetic Counselors (NSGC) website are two good resources for you or your baby's health care provider to use to identify local specialists.
Elle Kate was diagnosed with NKH shortly after birth. While she still has some health problems she has come a long way since the early health problems she experienced in the first month of her life. Read her story here.
The NKH Crusaders, founded by the parents of a child diagnosed with NKH after years of health problems share their story, and the story of other children they have met through their organization. Read their stories here.