NGLY1 deficiency

NGLY1 deficiency is a genetic condition and there is no cure. A person will never outgrow the disorder. Because so few children have been identified with this disorder, it is hard to say how the symptoms will affect children as they grow older. People with NGLY1 deficiency will receive periodic evaluations to see whether the disorder progresses, and what specific signs and symptoms are present.

The nonprofit organization NGLY1.org can provide more information and a patient handbook about this disorder.

NGLY1 deficiency is caused by a change in a gene called NGLY1. The NGLY1 gene produces an enzyme known as n-glycanase, which is required to rid the body of other proteins that are damaged (misfolded). The way that this enzyme rids the body of damaged proteins is called deglycosylation. Because of the change in the NGLY1 gene, children with NGLY1 deficiency do not have enough n-glycanase, and damaged proteins build up in various cells in the body, breaking down the cells and damaging the surrounding tissue. Abnormal proteins build up in brain tissue, eye tissue, liver tissue, etc. This causes the various symptoms of NGLY1 deficiency.

Support groups can put you in contact with other people or families that have NGLY1 deficiency. There are only about 65 people who have been identified with this disorder. A support group called NGLY1.org is the best place to find other children and families dealing with this disorder.

There are also online communities for rare disorders such as RareConnect, RareShare, or Inspire, which allow individuals and parents to share experiences and advice about dealing with rare disorders.

The medical cost of NGLY1 deficiency can be significant. Some families lack the resources necessary to provide for a chronically ill or disabled child. There are several organizations that provide financial assistance.

The Social Security Administration (SSA) in the United States provides disability benefits for people who qualify. NGLY1 deficiency is not listed in the publication called the Disability Evaluation Under Social Security, also called the "Blue Book." However, people with NGLY1 deficiency may still qualify for assistance if they have certain symptoms that qualify.

The SSA also has a program called Supplemental Security Income, which is designed to help disabled people with little or no income. It is mainly set up to help with basic necessities.

The National Organization for Rare Disorders has links to organizations that can also provide financial assistance.

The National Human Genome Research Institute has extensive information on finding financial aid for medical treatment and services.

Taking care of someone with a long-term or chronic condition can be tiring and challenging and NGLY1 deficiency is no exception. If you are a caregiver in need of support, try to take time for yourself, set aside time for personal counseling, or look for other resources at the Caregiver Action Network. This organization works to improve the quality of life for people who care for loved ones with chronic conditions, disabilities, disease, or the frailties of old age. Support groups can also help provide support and advice for caregivers.

Support groups for NGLY1 deficiency include NGLY1.org.

General tips for caregivers from a psychologist with experience in the field can be found in a ThinkGenetic article here: https://news.thinkgenetic.com/2017/09/27/resilience-the-art-of-caregiving-preparing-for-curves-bumps-and-wrong-turns-by-adding-a-dose-of-resilience/.

The age of onset, which is when symptoms first become apparent, can vary in each person with NGLY1 deficiency. NGLY1 is a genetic disorder and people are born with it. Symptoms associated with the disorder may be there at birth or in infancy, but doctors may not recognize them or may not realize that they are caused by NGLY1 deficiency. Many doctors are unfamiliar with NGLY1 deficiency and may not consider the disorder when trying to figure out why a child is sick. Diagnoses of NGLY1 deficiency have ranged from three years to 20 years of age.

Eye drops are extremely important for infants and children with NGLY1 deficiency. Because they cannot produce tears, they are at risk for inflammation and irritation of the eyes as well as sores forming on the conjunctiva, the clear membrane that lines the eyes. Eye drops help to lubricate the eyes and keep them healthy.

Some infants may have problems feeding and swallowing. Doctors may decide that these infants require a feeding tube that can be used to ensure they receive enough food and nutrients.

There are no medications approved for NGLY1 deficiency. Medications that prevent seizures, called anticonvulsants or anti-epileptics, may be prescribed, but sometimes are not effective.

The support group NGLY1.org may be a source of more information on treatment options for NGLY1 deficiency.

Several different tests may be used to help diagnose NGLY1 deficiency, but the disorder is confirmed through molecular genetic testing. Molecular genetic testing can be used to study the NGLY1 gene to identify variations or changes in the gene that lead to the disorder. This can include sequence analysis, where a part or sequence of DNA within a gene is examined; or deletion/duplication analysis, where missing or extra regions of DNA are looked for within a specific gene.

Blood tests can be performed to see whether certain liver enzymes such as aspartate transaminase (AST) and alanine transaminase (ALT) are higher than normal. This can help doctors suspect a diagnosis of NGLY1 deficiency in younger children. The levels of these enzymes becomes normal as children grow older, so testing for them in older children is not done.

Physicians may also order a urine test. People with NGLY1 deficiency have abnormalities in oligosaccharides (long sugar chains). The laboratory can look at your urine to see if your oligosaccharides are abnormal.

Rare diseases that affect multiple organ systems, such as NGLY1 deficiency, can benefit from a multidisciplinary approach. This approach involves healthcare professionals with specialized skills and expertise. They work together to make treatment recommendations and to provide quality care to individuals and families.

The specific doctors that will be a person’s medical team will depend upon the specific symptoms that develop. A multidisciplinary team can include a doctor who specializes in disorders of the brain and central nervous system in children (pediatric neurologists), doctors who specialize in the eyes (ophthalmologists), doctors who specialize in the liver (hepatologists), doctors who specialize in the muscles and skeleton (orthopedists), and doctors who specialize in the gastrointestinal system (gastroenterologists).

Other types of doctors and medical personnel that may see a child with NGLY1 deficiency include a medical geneticist, genetic counselor, speech pathologist, physical therapist, and psychologist.

Your family physician or pediatrician can help you locate specialists in your area.

NGLY1 deficiency can cause several types of seizures. The onset of seizures have ranged from a couple months of age to about 10 years of age. Specific types include atonic seizures, in which there is a sudden loss of muscle strength; tonic seizures, in which muscle tone increases causing the arms, legs, and body to stiffen; absence seizures, in which there is a brief loss or lapse in awareness sometimes with staring; and gelastic seizures, in which there is a sudden burst of energy, often with laughing or crying. Some infants may have infantile spasms, in which there a sudden, jerky movements or muscle contractions.

The nonprofit organization NGLY1.org has information and advice about NGLY1 deficiency. The Epilepsy Foundation can provide information, support and advice about seizures.

Children with NGLY1 deficiency may need lots of medical equipment. To name just a few, parents may need to get: a pediatric wheelchair, adaptive strollers, adaptive chairs, walkers and gait trainer, toilet chairs, and bath chairs. They may need splints, braces, glasses or hearing aids as well. Some children may also require cooling vests. These devices can be expensive and may or may not be covered by insurance. As children get older, special communication devices may be necessary and some parents will want to modify their homes or their cars in order to better accommodate their children. Certain support groups and nonprofits provide information on medical equipment. A doctor or other medical specialist can work with families to get or advocate for medical equipment.

Because NGLY1 deficiency has only been identified in about 60 children, it is hard to make predictions about prognosis. Most children seem to be healthy overall despite the complications associated with the disorder. A few children have passed away because of complications due to seizures or frequent respiratory infections. Doctors are studying the disorder to learn more about the underlying processes that cause the symptoms in hopes of developing better treatments.

The nonprofit organization NGLY1.org may have up-to-date information on research and treatments for NGLY1 deficiency.

NGLY1 deficiency is an extremely rare disorder characterized by a variety of different symptoms that can affect multiple organ systems of the body. Three characteristic findings of this disorder are varying degrees of intellectual disability, movement disorders, and a condition called alacrima. Movement disorders are any disorder in which there are problems with the speed, quality, or ease of making voluntary movements. Alacrima is a condition in which infants or children cannot produce tears when they cry, or they can produce tears but only infrequently. This can cause other issues with the eyes. Every person with this disorder does not necessarily have the same symptoms or features. There can be people who are mildly affected and others who have more severe health problems. NGLY1 deficiency is an autosomal recessive disorder meaning that for a person to have the disorder, they have to inherit two changed copies, or two variants, of a specific gene called NGLY1. There are only about 60 people known to have this disorder, so researchers and physicians are still learning about NGLY1 deficiency.

Doctors are still learning about NGLY1 deficiency and, as more children are diagnosed, they will develop a more complete picture of this disorder. Generally, there are three main or characteristic findings. These include varying degrees of intellectual disability, certain movement disorders, and a condition called alacrima. Alacrima is a condition in which infants or children cannot produce tears when they cry, or they can produce tears but only very infrequently. This can cause other issues with the eyes.

NGLY1 deficiency can potentially affect multiple organ systems of the body. Symptoms can include delays in reaching developmental milestones like sitting up or walking, seizures, abnormally small hands or feet, and hearing loss.

How NGLY1 deficiency affects one child can be very different from how it affects another child. Every child is unique and the signs and symptoms associated with the disorder in each specific child will be different.

For more information on the various health problems that can be associated with NGLY1 deficiency, please see the "Symptoms" section. The nonprofit organization NGLY1.org has information about this disorder.

NGLY1 deficiency is caused by gene changes in the NGLY1 gene. The NGLY1 gene produces an enzyme that helps to remove damaged (misfolded) proteins from the body. People have about 20,000-25,000 genes in their bodies. Our genes contain our body’s genetic information, called DNA; genes are segments of DNA found on chromosomes. Genes are inherited from our parents and passed on to our children. Genes are like our body’s instruction manual – they control the growth, development, and normal function of the body. Genes produce specific proteins that the body needs to grow and work properly. When there is an unexpected change in a gene, the protein that the gene produces may be absent or not work properly, or be overproduced.

To find a medical professional nearby who can discuss information about gene changes in NGLY1 deficiency, the National Society of Genetic Counselors website offers a Find a Genetic Counselor tool on its website. This can help people find a genetic counselor within the United States. The Genetics Home Reference website has information on the NGLY1 gene.

A "variant" is another word for a change in a gene. Sometimes these changes are not associated with causing a genetic disease or condition, and other times they are. Variants can be benign (not disease causing), pathogenic (disease causing), or of unknown significance (possibly disease causing). Looking at a person’s genetic testing report can be helpful to know what type of variant or genetic change someone has inherited for NGLY1 deficiency. If a person has this disorder, they have two different disease causing variants in their NGLY1 genes.

Visit the National Society of Genetic Counselors, which has a Find A Genetic Counselor tool on its website. This can help people find a genetic counselor within the United States.

Individuals with NGLY1 deficiency cannot produce tears (alacrima) or do not produce enough tears (hypocrima). It is very important to keep the eyes moist and lubricated. People with this disorder will need to receive lubricating eye drops and bland ointments frequently throughout the day and night. All children should receive a complete examination from an eye doctor to assess the condition of their eyes. Without treatment, lots of problems can develop including scarring of the cornea (thin, transparent membrane that lines the front of the eye).

Talk to your child’s physician or eye specialist (ophthalmologist) to set up a treatment plan on how to best handle and treat alacrima and hypocrima.

NGLY1 deficiency demands a lot of time and focus from parents. As with similar disorders, it is easy for healthy siblings to feel as if they have been pushed aside. Although studies have shown that siblings of children with chronic illness tend to develop strong levels of compassion and empathy, these studies have also shown that siblings can develop feelings of jealousy, anger, and high levels of anxiety. Parents can work with siblings by having clearly defined roles and responsibilities within the family structure. Parents are encouraged to make time for activities especially for healthy siblings and to talk with and encourage healthy siblings to address their concerns and feelings. Some children may benefit from support outside of the immediate family including therapists or doctors. The Sibling Support Project is a nonprofit organization that serves the concerns and needs of siblings of people with special health, developmental, and mental health needs.

Infants with NGLY1 deficiency may weigh much less than most babies do when they are born (low birth weight). Some infants lack muscle tone, this is called hypotonia. Infants with hypotonia are described as being ‘excessively floppy.’

Infants usually have good appetites, but may fail to gain weight and grow as well as they should. Some infants develop microcephaly – this is a condition in which the baby’s head is smaller than it should be. Infants may experience delays in reaching developmental milestones like sitting up or crawling. They may not development speech. Seizures are common in NGLY1 deficiency and can start as early as two months of age. Some infants may have abnormal muscle contractions and their muscles may tremble. Infants with NGLY1 deficiency may not be able to produce tears when they cry, this is called alacrima.

It is difficult for doctors to predict which symptoms an infant will develop or how severe those symptoms will be.

If you would like to learn more about NGLY1 deficiency, speak to your doctor about a referral to a genetic counselor. In the United States, you can find a genetic counselor near you by using the Find a Genetic Counselor Tool on the National Society of Genetic Counselors website. A nonprofit organization called NGLY1.org also has information on NGLY1 deficiency.

How NGLY1 deficiency affects one child can differ very much from how it affects another. Children with NGLY1 deficiency often have intellectual disability. Some have a below average IQ, while other children have severe intellectual disability. They often do not speak or only speak a few words. There are delays in learning to walk and some children may not be able to walk or require help to walk.

Children with NGLY1 deficiency do not produce tears when they cry, or they only sometimes produce tears. This can cause problems and inflammation within the eyes and, if not treated, can sometimes affect vision.

Children also have movement disorders. They may have muscle spasms, tremors, twitching and/or jerking movements, and abnormal muscle contractions.

Some children may have hands or feet that are very small and their joints may be loose and have a greater range of motion than normal. Their spines may curve sideways, a condition called scoliosis, and the hips may be more likely to pop out of their joints or dislocate.

Children can have hearing loss, sleep disturbances, and they may be unable to sweat properly. Children who can’t sweat properly are more likely to become overheated.

If you would like to learn more about NGLY1 deficiency, speak to your doctor about a referral to a genetic counselor. In the United States, you can find a genetic counselor near you by using the Find a Genetic Counselor Tool on the National Society of Genetic Counselors website. A nonprofit organization called NGLY1.org also has information on NGLY1 deficiency.

After a diagnosis of NGLY1 is confirmed, families should seek a medical consultation with a physician such as a metabolic genetic specialist with experience in the disorder. NGLY1.org is a support group that may be able to help find physicians or medical centers with experience in treating this disorder.

People diagnosed with NGLY1 deficiency will go through a series of tests to see how far along the disease is. These tests will tell a physician what parts of the body are affected and to what extent. Some tests or examinations a doctor will run will include tests that evaluate a child’s eyes, the health of bones and the skeleton, their ability to sweat, and an overall assessment of neurological function and capabilities. Sometimes, doctors may run a sleep study.

Other initial steps will depend on how the disorder is affecting a person. Families should see a genetic counselor to help understand the genetic aspects of this disorder. Visit the National Society of Genetic Counselors, which has a Find A Genetic Counselor tool on its website. This can help people find a genetic counselor within the United States.

In a family with NGLY1 deficiency, additional testing can be done to see whether at-risk family members are carriers for the disorder. However, the specific gene changes in the NGLY1 gene in that family must be known. If known, all siblings of an affected child can be tested to see whether they have the disorder or whether they are carriers. Knowing their carrier status will allow family members to better understand their risk to have their own child with NGLY1 deficiency. A newborn child in such a family must be tested either through a test that looks for a gene change (if known for that family). A genetic counselor or physician with experience in this disorder can provide advice about how a diagnosis can impact other family members. To find a genetic counselor near you, visit the National Society of Genetic Counselors Find a Genetic Counselor website.

Some physicians may recommend that children with NGLY1 deficiency receive an evaluation by a developmental (behavioral) pediatrician. These are pediatricians who specialize in and have training dealing with issues beyond those seen in most children. These pediatricians can help address any issues in a child’s development – whether it is an aspect of social, behavioral, mental, or emotional development. You can talk to your doctor and medical team about receiving an evaluation by a developmental pediatrician.

As of 2018, newborn screening for NGLY1 deficiency is not offered in any U.S. states. However, prenatal testing is possible if the baby’s parent is known to have a change (or mutation) in the NGLY1 gene. The genetic test checks to see if the baby has the same mutation as the parent before the baby is born. After a child is born, he or she can get tested with a blood or saliva sample if they have symptoms, just as an adult would.

If you would like to learn more about prenatal genetic testing for NGLY1 deficiency, speak to your doctor about a referral to a genetic counselor. In the U.S., you can find a genetic counselor near you by using the Find a Genetic Counselor Tool on the National Society of Genetic Counselors website.

As of April 2018, there are no ongoing clinical trials for NGLY1 deficiency. The best way to find information about clinical trials is to visit the website, www.clinicaltrials.gov. This is a government website that provides regularly updated information about federally and privately supported research and clinical trials. This is not an exhaustive list of current research.

The nonprofit patient organization, NGLY1.org, collaborates with the National Institutes of Health (NIH) and is a great source of information. As of April 2018, there are several affected individuals who are participating in two important protocols where researchers are "gaining valuable insights in the characteristic symptoms and natural progression of the disease and laying the groundwork for future therapeutic approaches."

As of 2018, there are no FDA-approved treatments for NGLY1 deficiency. Because of this, doctors will try and treat the symptoms of the disorder individually.

In infants, this symptomatic treatment may include using a feeding tube to ensure an infant receives enough food and nutrition. Eye drops are important to lubricate the eyes for infants and children who can’t produce tears. Some children may have problems sweating. These children need to have access to water and a cool environment. Drugs that stop seizures called anti-epileptics may be used, but sometimes seizures persist. Orthostatic devices may be recommended for children who have problems walking.

Supportive services for children with NGLY1 deficiency include physical therapy to help strengthen muscles and manage movement disorders and special education classes.

There are several potential symptoms associated with NGLY1 including scoliosis, sleep apnea, constipation, and hearing loss that are treated with standard guidelines. This means that children with NGLY1 deficiency are treated in the same way children without the disorder are. Your doctor or medical team can share information and advice on how these conditions are treated.

Research is ongoing to find more effective treatment options and potentially a cure for NGLY1 deficiency. A nonprofit organization called NGLY1.org may have more information about this disorder and researchers who are studying this disorder.

Visit the National Society of Genetic Counselors, which has a Find A Genetic Counselor tool on its website. This can help people find a genetic counselor within the United States.

Carriers of an NGLY1 gene with an alteration that causes NGLY1 deficiency do not develop symptoms of the disorder. They are at risk of passing the altered gene on to their children who would also be carriers. If the other parent also carried an altered NGLY1 gene, then there would be a 25% chance for each pregnancy that the child will have the disorder, a 50% chance the child would be a carrier, and a 25% chance that the child would not be a carrier nor have the disorder.

To find a nearby medical professional who can discuss information about gene changes in NGLY1 deficiency, the National Society of Genetic Counselors website offers a Find a Genetic Counselor tool on its website. This can help people find a genetic counselor within the United States. The Genetics Home Reference website has information on the NGLY1 gene.

NGLY1 deficiency is inherited in an autosomal recessive manner. This is one way in which a disorder or trait can be passed down through a family. Everyone has two copies of the NGLY1 gene; one received from their father and one from their mother. Autosomal recessive inheritance means that a person receives a non-working copy of the NGLY1 gene from both parents. The parents have one working copy of the gene and one non-working copy; they are carriers for NGLY1 deficiency. Carriers do not develop symptoms of the disorder. If two people who are carriers have NGLY1 deficiency have a child, there is a 25% chance with each pregnancy that the child will have the disorder, and a 50% chance the child will also be a carrier. If you have a family member with NGLY1 deficiency and you would like to know if you are a carrier, talk to your doctor or meet with a genetic counselor to discuss testing options. Visit the National Society of Genetic Counselors, which has a Find A Genetic Counselor tool on its website. This can help people find a genetic counselor within the United States.

NGLY1 deficiency is classified as a disorder of deglycosylation, which is part of a larger group of disorders called the congenital disorders of glycosylation. Congenital means that it is present at birth, and not acquired during life. Glycosylation is a normal process in the body. It is a complex chemical process. It involves glycans, which are called sugar trees. Glycosylation involves the creating, altering, and chemically attaching these sugar trees to certain proteins or fats. This process is very important for the proper health and development of various systems of the body, particularly the central nervous system. Deglycosylation in the process in which these sugar trees are removed from proteins. This is a vital step in helping the body to remove damaged proteins from the body.

There are about 80 different types of congenital disorders of glycosylation. Researchers are studying and learning more about these disorders. For more information, you can contact the nonprofit organizations, [link url="NGLY1.org” target=”_blank”>NGLY1.org for NGLY1 specifically, or CDG Care for an overview on congenital disorders of glycosylation.

Infants and children with NGLY1 deficiency may be unable to produce tears when they cry (called alacrima), or produce only a few tears when they cry (called hypocrima). This symptom is not unique to NGLY1 deficiency, but it is a rare symptom that only occurs in certain syndromes. Tears are important for the health and function of the eyes. There are glands in the eyes called lacrimal glands that produce tears. Tears keep the eyes moist and help to wash out dust and other foreign materials from the eyes.

Because individuals with NGLY1 deficiency do not produce tears, their eyes will become red and irritated. If not treated, lots of problems can develop. These problems can include blepharitis (inflammation of the eyelids), infection, and irritation of the eyes. Sometimes open sores called corneal ulcerations can form on the cornea. Scarring of the cornea can also develop. The cornea is transparent membrane that covers the eye.

Individuals with NGLY1 deficiency who cannot produce tears need to receive eye drops to protect and lubricate the eyes. In addition to a general physician or pediatrician, individuals with NGLY1 deficiency should be seen by an eye specialist, called an ophthalmologist. Your doctor can provide a recommendation to an eye specialist in your area.

The nonprofit organization NGLY1.org has a newsletter that keeps families up to date on research, news, and events related to NGLY1 deficiency. You can contact them at their website.

NGLY1 deficiency is a rare genetic disorder with less than 100 documented diagnoses. Because of its rarity, most people, and even most physicians, are not familiar with NGLY1 deficiency. Support groups offer information and support for NGLY1 deficiency. A support group may also have advice and resources to help families and people raise awareness of a disorder. NGLY1.org is a support group for this disorder. Rare disease organizations like the National Organization for Rare Disorders and Global Genes may also be able to help spread information and awareness of NGLY1 deficiency.

Support groups often have information about how to support research endeavors and most accept donations toward research. Some groups focus specifically on supporting research. Support groups for NGLY1 deficiency include NGLY1.org. Umbrella organizations like the National Organization for Rare Disorders and Global Genes also support research. Charity navigator is an independent organization that evaluates charitable organizations. Visit www.charitynavigator.org to learn about a specific charity.

Genetic testing for NGLY1 deficiency is available. If you have symptoms and/or a family history of the disorder, a genetic counselor or a geneticist can usually order a genetic test for you. You can give blood or saliva, although there are other samples that can be used to test your DNA (less commonly). The sample is sent to a laboratory that will study your DNA in detail. The test will usually check to see if there are any changes (or mutations) in the NGLY1 gene that could cause it to not work properly. The genetic counselor will receive the results and explain to you what they mean in detail. It is possible that the testing will not detect a gene mutation.

In young children, certain liver enzymes may be elevated. Blood tests can be performed to see whether these enzymes, aspartate transaminase (AST) and alanine transaminase (ALT) are higher than normal in the blood. This can help doctors reach a diagnosis of NGLY1 deficiency. The levels of these enzymes becomes normal as children grow older, so testing for them in older children is not done.

Physicians may also order a urine test. People with NGLY1 deficiency have abnormalities in oligosaccharides (long sugar chains). The laboratory can look at your urine to see if your oligosaccharides are abnormal.

If you would like to learn more about testing for NGLY1 deficiency, speak to your doctor about a referral to a genetic counselor. In the United States, you can find a genetic counselor near you by using the Find a Genetic Counselor Tool on the National Society of Genetic Counselors website. A nonprofit organization called NGLY1.org also has information on genetic testing for NGLY1 deficiency.

To learn about ongoing clinical research on NGLY1 deficiency, ask a physician who specializes in the disorder. Genetic counselors and medical geneticists are also excellent sources of information about ongoing clinical trials and can offer advice about the pros and cons about participating in such a trial. The National Society of Genetic Counselors website offers a Find a Genetic Counselor tool on its website. This can help people find a genetic counselor within the United States.

Ongoing studies for NGLY1 deficiency can also be found on clinicaltrials.gov, a service of the U.S. National Institutes of Health. The website allows people to enter a disease name into a search box to see current or completed studies into a particular disorder. In Europe, the EU Clinical Trial Register performs a similar service.

Support groups also have information about ongoing clinical trials as well as information and advice about participating in clinical trials. NGLY1.org is a nonprofit support group for this disorder. To stay up-to-date, you can sign up for this group’s newsletter, or follow their social media.

While the symptoms of NGLY1 deficiency can vary, most children do not learn to walk or talk. Children may need special accommodations in school. They are eligible for an individual education plan (IEP) or a 504 plan. An IEP is a document that helps to guide the education of a child with a disability or special needs. The plan is individualized for each student. A 504 plan ensures that students with disabilities can fully participate in school and have access to the same educational opportunities as other children. Parents are encouraged to provide their child’s school with a packet of information on NGLY1 deficiency and to work with school officials including teachers, nurses, psychologists, the principal, and other professionals.

Global Genes, a rare disease advocacy organization, has a RARE Toolkit that advises parents on advocating for their children at their school.

The U.S. Department of Education has information on individual education plans and on 504 plans.

The nonprofit organization, NGLY1.org, can provide information and support regarding these issues for children with NGLY1 deficiency as they enter school.

According to NGLY1.org, as of January 2018, there are about 65 people who have been identified with NGLY1 deficiency. The incidence and prevalence of this disorder is unknown.

Incidence refers to the number of new people diagnosed with a disease over a given period of time (usually one year). Prevalence refers to the number of people who have a disorder in a given population at a specific time. Many people who have this disorder may be misdiagnosed, or may be labeled as undiagnosed. As more is learned about NGLY1 deficiency, more people with this disorder will likely be identified.

Yes, everyone with NGLY1 deficiency has two gene mutations in the NGLY1 gene. Everyone has two copies of the gene associated with NGLY1 deficiency; they receive one from their father and one from their mother. This disorder is caused by changes (or mutations) in the NGLY1 gene. NGLY1 deficiency is passed down in what is called an autosomal recessive manner. This means that someone needs two gene mutations to develop NGLY1 deficiency, and they receive one copy of each mutation from their parents. Each parent is a carrier. Carriers do not develop symptoms of the disorder.

If two carriers for NGLY1 deficiency have children together, they have a 1 in 4 (or 2 5%) chance to have an affected child, with each pregnancy together. They have a 1 in 2 (or 50%) chance to have a child that is a carrier, just like them. They also have a 1 in 4 (or 25%) chance to have a child that is not a carrier and does not have NGLY1 deficiency. These odds are the same in every pregnancy the carriers have together. No parent has control over which genes they pass, or do not pass, to their children.

People with NGLY1 deficiency may be the first in a family to be diagnosed with the condition or may only have siblings with it. Their parents each have one altered NGLY1 gene and it is possible that is one altered gene has run in the family. So when a child inherits the altered gene from both parents the disorder seems to pop up out of the blue. People who have an autosomal recessive disorder are very unlikely to have a child with the condition.

You did not do anything to cause NGLY1 deficiency in your child. You also could not have done anything to prevent this from happening in your child. When an egg and a sperm first meet to form a baby, there is genetic information from the mother and from the father that combine together. Parents of a child with NGLY1 deficiency are carriers for the disorder and have a 25% risk with each pregnancy to have a child with NGLY1 deficiency.

Talk to a genetic counselor to learn more about the genetics and inheritance of NGLY1 deficiency. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website. This can help parents find a genetic counselor in the United States.

No, if children have this disorder, it means they have a harmful change in both copies of their NGLY1 genes.

Some children with NGLY1 deficiency may have problems sweating, called hypohidrosis. These children should avoid situations where they may become too hot, or be unable to cool down when they need to. These children need access to water to remain hydrated, and should have access to a cool environment as well. Sometimes, a device called a cooling vest can help. Your doctors can provide advice and information about hypohidrosis and the best ways to manage this condition.

Whether or not to make modifications to the home of a child with NGLY1 deficiency is an individual decision. As children age, they may become less mobile, have difficulty speaking, and have other complications that can be better dealt with by adapting the home. Modifications can include altering the home so everything the child needs is on one floor. The nonprofit organization NGLY1.org may have advice about considering home modifications for families dealing with NGLY1 deficiency.

NGLY1 deficiency may be known by a few other names, including:

As of May 2018, there is an international NGLY1 deficiency support group based in the United States called NGLY1.org. This organization eliminates the challenges of N-glycanase deficiency through research, awareness, and support.

Larger umbrella groups may be able to provide networking, referrals, information and support for NGLY1 deficiency. These organizations include the National Organization for Rare Disorders https://rarediseases.org/; Global Genes https://globalgenes.org/; and the Genetic Alliance http://www.geneticalliance.org/.

Infants with NGLY1 deficiency often show symptoms within the early stages of life. The first few years of a child’s life are critically important to a child’s development. States have federally-funded early intervention programs that support families that have concerns or issues with their children’s development up to the age of three. Some states continue to offer early intervention programs beyond the age of three. Other states will transition a child into school-based programs that can be provided at home. In some states, a child may be eligible for early intervention services at no charge. Other states may charge a fee, depending on the agencies involved.

The U.S. Centers for Disease Control and Prevention have information about early intervention programs and a listing of what each state offers.

While there are no centers of excellence for NGLY1 deficiency as of April 2018, Gregory Enns, MD, FACMG of Stanford University is the corresponding author of the journal article describing the discovery and confirmation of NGLY1 deficiency as a distinct disorder. This paper involved work with a large team of scientists from several different medical institutions around the world. Cristina Lam, MD, FACMG, is an attending physician at Seattle Children’s Hospital (SCH) and Assistant Professor in the Department of Pediatrics at the University of Washington School of Medicine (UW) and contributed to information about this disorder.

One of the best ways to find a treatment center or physician with experience in treating a rare disorder is to contact a national support group. NGLY1.org is an international support group based in the United States for NGLY1 deficiency.

Researchers are learning more and more about NGLY1 as more children are identified with the disorder. As they learn more about the underlying causes of this disorder, they may be able to study new therapies. As of May 2018, one potential treatment under investigation is a certain proton pump inhibitor. Proton pump inhibitors are drugs that block the production of acid in the stomach. They are used to treat indigestion and heartburn. Researchers are looking at certain types of these drugs as potential therapies for NGLY1 deficiency. More research including clinical trials are necessary to determine that any medication is safe and effective in the long-term. The nonprofit organization called NGLY1.org may have information on research into treatments for NGLY1 deficiency.

Because so few children with NGLY1 deficiency have been identified, it is hard to make broad generalizations about this disorder. However, most children have been very sociable, have good senses of humor, and seek to connect with people.