Tmem165-cdg is a very rare inherited condition that affects how the body processes sugars needed to build and maintain tissues. It usually becomes noticeable in infancy or early childhood, and early signs of Tmem165-cdg can include slow growth, low muscle tone, developmental delay, and bone or joint changes. Not everyone will have the same experience. Tmem165-cdg is lifelong, and some children have more severe medical problems, so the outlook can vary depending on which body systems are affected. Treatment does not cure Tmem165-cdg, but supportive care such as physical, occupational, and speech therapy, nutrition support, and regular follow-up with specialists can help manage its features.
How many people live with Tmem165-cdg?
TMEM165-CDG is so rare that no reliable estimate of how many people live with it worldwide or in the United States is consistently reported by a single authoritative source. Orphanet lists the condition’s prevalence as unknown, and a separate U.S. estimate does not appear to be widely reported (Orphanet, 2025).
Overview
Tmem165-cdgSymptoms
TMEM165-CDG usually causes signs in infancy, including poor growth, low muscle tone, developmental delay, and feeding problems. Many children also have bone changes, liver problems, or unusual blood test results, but features can vary from person to person.
Outlook and prognosis
Outlook in Tmem165-cdg varies, but many living with Tmem165-cdg need ongoing support for growth, development, and daily functioning. Early treatment can improve comfort and nutrition. Prognosis depends mainly on symptom severity and which organs are affected.
Causes and risk factors
Tmem165-cdg is caused by changes in both copies of the TMEM165 gene. It is usually inherited from two carrier parents, so family history can raise the chance. Lifestyle does not cause Tmem165-cdg, though other health stresses can affect severity.
Genetic influences
Genetics are central to Tmem165-cdg. It is caused by changes in both copies of the TMEM165 gene, usually inherited from two carrier parents, so genetic testing is key for diagnosis and family planning.
Diagnosis
Diagnosis of TMEM165-CDG usually starts with clinical features and lab findings that suggest a glycosylation disorder. Doctors then confirm the genetic diagnosis of TMEM165-CDG with genetic tests, and sometimes use imaging or other organ-specific tests.
Treatment and drugs
Treatment for Tmem165-cdg focuses on day-to-day needs and careful follow-up with a metabolic specialist. Many living with Tmem165-cdg benefit from physical, occupational, and speech therapy, nutrition support, and treatment for seizures or growth problems. In some cases, galactose supplements may help.
Symptoms
Many living with Tmem165-cdg are smaller than expected for age and may have bone and joint differences that affect movement, comfort, and stamina. Low muscle tone and delays in sitting, walking, speech, or learning are also common. Features vary from person to person and can change over time. When families ask about the early features of Tmem165-cdg, slow growth, low muscle tone, and delayed motor milestones are often among the first signs noticed.
Children with Tmem165-cdg often grow more slowly than expected and may be much shorter than their peers. Some also have trouble gaining weight well, especially in infancy and early childhood.
Tmem165-cdg often affects how bones develop, which can lead to a curved spine, hip problems, knock knees, or a chest shape that looks different. Day to day, this can make standing, walking, or keeping up with play more tiring.
Some people have joints that are stiff or do not move through a full range, especially in the hips, knees, or fingers. Tasks like dressing, climbing stairs, or grasping small objects may take more effort.
Babies and children may feel floppy or seem less steady because their muscles have lower tone. This can affect posture, balance, and endurance, and it often delays rolling, sitting, or walking.
How people usually first notice Tmem165-cdg?
TMEM165-CDG is usually first noticed in infancy or early childhood, often because a baby is not growing as expected, has low muscle tone, feeding problems, or delays in learning to sit, crawl, walk, or speak. Some families and doctors first notice TMEM165-CDG because of liver problems, unusually low blood sugar, or changes in the bones or skeleton that show up on early checkups or imaging. The first signs of TMEM165-CDG can vary from child to child, but the pattern is often a mix of developmental delay and body-wide medical issues that lead doctors to order specialized genetic and metabolic testing.
Types of Tmem165-cdg
No distinct types of Tmem165-cdg are widely recognized.
Can I slow down the onset of symptoms?
No, at this time there is no good evidence that lifestyle changes or routine medical treatment can meaningfully delay the start of symptoms in TMEM165-CDG. This is a rare inherited condition that is usually present from birth or begins very early in life, so things like diet, exercise, sleep, or supplements have not been shown to prevent it or push symptoms back, although early specialist follow-up can help spot and manage problems sooner. Research into more targeted treatments is ongoing, and while that does not change the current outlook, staying connected with an experienced care team can still make a real difference in day-to-day health.
What genetics can tell you about symptoms
In TMEM165-CDG, changes in both copies of the TMEM165 gene are the known cause of the condition, and genetics can confirm that a person’s symptoms are part of this disorder. People with TMEM165-CDG can have a fairly wide range of symptoms, and the exact gene changes may help explain some differences in which problems show up, how severe they are, and how early they begin, but this link is still not clear in every case because the condition is very rare. In general, genetics gives important clues about the cause and possible pattern of symptoms, but it usually cannot predict the full day-to-day course for any one person.
Causes and risk factors
Tmem165-cdg is caused by harmful changes in both copies of the TMEM165 gene, usually one inherited from each parent. Family history matters, and if both parents carry a changed copy, each pregnancy has a 1 in 4 chance of Tmem165-cdg. Parents often do not know they are carriers because carriers usually have no symptoms. Diet, exercise, or something during pregnancy are not known to cause it, but other illnesses and nutrition can affect how severe symptoms of Tmem165-cdg become. Researchers are still learning how these pieces fit together.
What are the most common causes or risk factors?
TMEM165-CDG is a rare inherited condition caused by changes in the TMEM165 gene, and it usually happens when a child inherits one nonworking copy from each parent. The main risk factors are having a family history of the condition or having parents who both carry a changed copy of this gene, even if the parents are healthy themselves. In some families, the chance is also higher when the parents are blood relatives, and there are no known lifestyle or environmental causes.
Environmental and biological risk factors
For TMEM165-CDG, there are no well-established environmental or non-genetic biological risk factors known to increase the chance of the condition occurring. Awareness of both biological and environmental influences helps you feel prepared, but for TMEM165-CDG, outside exposures and routine maternal health factors have not been shown to play a proven role. Because this condition is rare and present from birth, patient information usually focuses on confirmed causes rather than modifiable risk factors.
Genetic risk factors
Tmem165-cdg happens when a child inherits disease-causing changes in both copies of the TMEM165 gene, which helps cells process certain proteins correctly. The main inherited risk is having two parents who each carry one changed copy; carrying a genetic change does not guarantee the condition will appear. Because carriers are usually healthy, Tmem165-cdg can show up in a family with no obvious warning signs until one child is diagnosed. In some families, genetic testing can help clarify the genetic causes of Tmem165-cdg and the chance of it happening again.
TMEM165 changes: Tmem165-cdg is caused by harmful changes in the TMEM165 gene. In most cases, both copies of this gene need to be affected for the condition to develop.
Recessive inheritance: Tmem165-cdg is inherited in an autosomal recessive pattern. This means a child receives one changed TMEM165 copy from each parent.
Carrier parents: People who carry one changed TMEM165 copy usually do not have symptoms. If both parents are carriers, each pregnancy has a 25% chance of Tmem165-cdg, a 50% chance of producing a carrier child, and a 25% chance of producing a child with no changed copies.
Family history: Having a child, brother, sister, or other close relative with Tmem165-cdg raises the chance that relatives may also be carriers. This can matter when families are planning future pregnancies or considering testing.
Shared ancestry: Parents who are related by blood, or who come from a small population with shared ancestry, may be more likely to carry the same rare TMEM165 change. That can increase the chance of Tmem165-cdg in a child.
Lifestyle risk factors
TMEM165-CDG is an inherited glycosylation disorder, so lifestyle habits do not cause it. Still, how lifestyle affects TMEM165-CDG can be important because nutrition, activity, sleep, illness prevention, and day-to-day care may influence growth, strength, comfort, and complication risk. The main lifestyle risk factors for TMEM165-CDG are usually factors that worsen symptoms or make supportive care harder rather than factors that trigger the disease itself.
Poor calorie or protein intake can worsen growth failure, low muscle mass, and fatigue in people with TMEM165-CDG. Feeding difficulties, restrictive eating, or dehydration may also make weakness, constipation, and recovery from illness harder.
Too little movement can lead to further loss of muscle strength, reduced endurance, and more joint stiffness when hypotonia or motor delay are present. Gentle, regular activity matched to ability may help preserve mobility, balance, and daily function.
Irregular or poor sleep can worsen daytime fatigue, attention, irritability, and coping with chronic symptoms. Good sleep routines may support energy, rehabilitation participation, and overall function in TMEM165-CDG.
Skipping routine hygiene, dental care, or practical infection-prevention habits can increase illness burden and set back nutrition, strength, and developmental progress. Viral or gastrointestinal illnesses may be especially disruptive when baseline feeding or growth is already fragile.
Risk prevention
For people living with Tmem165-cdg, true prevention of the condition itself is not currently possible because it is a genetic condition present from birth. Prevention is mainly about lowering the risk of complications, spotting problems early, and supporting growth, nutrition, bones, and development over time. Different people need different prevention strategies—there’s no single formula.
If Tmem165-cdg runs in a family, genetic counseling can help clarify the chance of it happening in a future pregnancy. Carrier testing and pregnancy planning may help some families understand their options.
Ongoing care with a metabolic or genetics team can help catch problems before they become more serious. This may include checks for growth, feeding, liver health, bone changes, hearing, vision, and development.
Many living with Tmem165-cdg benefit from early feeding support to help prevent poor growth and vitamin or mineral shortfalls. If eating is tiring or slow, a dietitian and medical team can help make meals safer and more effective.
Vaccines, handwashing, and early treatment of infections can help reduce stress on the body in people with Tmem165-cdg. Prevention works best when combined with regular check-ups.
Can you prevent Tmem165-cdg?
TMEM165-CDG is caused by an inherited gene change and is present from birth, so it cannot be prevented with diet, lifestyle changes, or routine medical care. If this condition runs in your family, meeting with a genetics specialist or genetic counselor before pregnancy may help you understand the chance of having a child with it and what testing options are available.
Transmission
TMEM165-CDG is not infectious, so it cannot spread from one person to another through touch, coughing, blood, food, or sex. Instead, how TMEM165-CDG is inherited is the key point: it usually happens when a child receives two altered copies of the TMEM165 gene, one from each parent.
Many parents of a child with TMEM165-CDG are healthy carriers, which means they have one altered copy and one working copy of the gene and do not have the condition themselves. If both parents are carriers, each pregnancy has a 1 in 4, or 25%, chance that the baby will have TMEM165-CDG.
When to test your genes
Genetic testing for TMEM165-CDG is most useful when a baby or child has a pattern of unexplained developmental delay, poor growth, low muscle tone, liver problems, or bone and joint changes. Early testing can confirm the diagnosis, guide supportive care, and help with family planning and genetic counseling.
Diagnosis
Tmem165-cdg is usually suspected when a baby or child has a pattern of growth, bone, liver, or developmental problems that do not fit a more common condition. Getting a diagnosis is often a turning point toward answers and support. Because this is a rare inherited disorder, the diagnosis of Tmem165-cdg often combines physical findings, lab results, and genetic testing.
Doctors look at the overall pattern of symptoms, such as poor growth, developmental delay, low muscle tone, feeding problems, and signs of liver or bone involvement. A careful exam can show whether the combination of findings suggests a congenital disorder of glycosylation rather than a more common childhood illness.
Specialized blood tests can check whether certain proteins are built with the usual sugar chains. These tests are often an important early clue in the genetic diagnosis of Tmem165-cdg, although results still need to be confirmed with other testing.
A DNA test can look for changes in the TMEM165 gene that cause the condition. This is the main way to confirm Tmem165-cdg after the clinical picture and lab findings raise concern.
X-rays or other scans may be used if there are concerns about bones, growth, or internal organs. These imaging findings do not diagnose Tmem165-cdg on their own, but they can support the diagnosis and help define how the condition is affecting the body.
How is Tmem165-cdg diagnosed?
Doctors usually suspect TMEM165-CDG from a pattern of health problems such as slow growth, developmental delay, and signs that the liver, bones, or blood may be affected. A key test is a blood test that checks whether the body is attaching sugar parts to proteins in the usual way, and other exams may be done to look at organs and overall development. The diagnosis is usually confirmed with genetic testing that looks for a harmful change in the TMEM165 gene.
Stages of Tmem165-cdg
Tmem165-cdg does not have defined progression stages. This is because it is a rare inherited condition that usually shows a pattern of ongoing features from early life, rather than moving through clear step-by-step phases over time. Doctors usually start with a conversation about symptoms, growth, development, and any problems affecting bones, muscles, or the liver, and the early symptoms of Tmem165-cdg can vary from one child to another. Diagnosis is usually confirmed with blood and urine tests, imaging or specialist exams when needed, and genetic testing, while follow-up focuses on tracking growth, movement, bones, and organ health over time.
Outlook and prognosis
Outlook in TMEM165-CDG is variable and depends largely on how severe the skeletal, growth, liver, and developmental problems are in each person. Many affected children survive into childhood and beyond, but they usually need long-term multidisciplinary care, and developmental progress may remain delayed. Reported complications can include significant bone disease, feeding difficulties, and liver involvement, which can worsen overall prognosis in more severely affected individuals. Because TMEM165-CDG is extremely rare, there is not yet enough published information to define a precise life expectancy, and mortality data are limited. Early recognition, supportive treatment, and careful monitoring for organ complications may improve quality of life and help reduce medical risks.
Long-term effects
Many living with TMEM165-CDG have long-term effects that touch growth, movement, learning, and bone health from early childhood onward. The pattern can vary, but this condition often affects several body systems at the same time, so day-to-day needs may change over the years. Long-term effects vary widely, and some people have milder challenges while others have more complex medical and developmental needs. Thinking about the long-term effects of TMEM165-CDG helps set realistic expectations for childhood, adolescence, and adult life.
Slow growth can continue over time, and many people with TMEM165-CDG remain shorter than expected for their age. Weight gain may also be difficult in some children, especially when feeding has been hard from early life.
Delays in speech, learning, and overall development often remain long term, although the degree can vary from person to person. Some may need ongoing support with communication, school skills, or daily tasks into adolescence and adulthood.
Low muscle tone and motor delay can affect posture, balance, and stamina over many years. For many, this can mean later walking, tiring easily with physical activity, or needing extra help with fine motor tasks such as writing or dressing.
Skeletal differences can become a major long-term feature of TMEM165-CDG, especially in people who develop bone shape or growth problems. These changes may affect height, joint alignment, walking comfort, and physical function as a child grows.
How is it to live with Tmem165-cdg?
Living with TMEM165-CDG can look very different from one person to another, but for many it means managing a mix of developmental delays, low muscle tone, growth and bone problems, and sometimes hearing or movement difficulties that can make everyday tasks, school, and physical activity more tiring or slower to master. Many people with TMEM165-CDG need ongoing therapy, regular medical follow-up, and extra support with communication, mobility, feeding, or daily routines, although strengths and independence can still grow over time. For families and other close caregivers, daily life often involves coordinating appointments, adapting the home and schedule, and providing hands-on help, which can be demanding, but clear routines, rehabilitation services, educational support, and community resources can make life more manageable and connected.
Treatment and drugs
TMEM165-CDG is usually treated with supportive care, which means focusing on the problems it causes rather than having a cure that fixes the underlying gene change. Treatment often looks different for each person, but it may include physical, occupational, or speech therapy, help with feeding and nutrition, and medicines or other care for issues such as seizures, growth problems, or low muscle tone. For many families, this can mean regular follow-up with several specialists, especially if early symptoms of TMEM165-CDG affect movement, learning, digestion, or bone health. Doctors also watch closely for complications over time so care can be adjusted as needs change. Because TMEM165-CDG is rare, treatment is usually individualized at a center familiar with congenital disorders of glycosylation.
Can you cure Tmem165-cdg?
No, there is no cure for TMEM165-CDG right now. Treatment focuses on managing the problems it causes and supporting growth, feeding, development, and other parts of health, which can improve daily life and help prevent some problems. In some people, a special sugar supplement called galactose may help, but it is not a cure and should only be used with guidance from a specialist.
Non-drug treatment
Daily care for people with Tmem165-cdg usually focuses on building strength, supporting development, and making eating and everyday activities easier. Because this condition can affect movement, growth, learning, and sometimes hearing or bones, treatment is usually tailored to the symptoms each person has. For many, treatment begins not at the pharmacy, but with regular therapy visits, nutrition support, and practical help at home and school. Not every approach works the same way, so care often changes over time as needs change.
Physical therapy can help with low muscle tone, balance problems, joint stiffness, and delayed motor skills. For many living with Tmem165-cdg, this may mean working on sitting, walking, stairs, or safer movement during daily routines.
Occupational therapy helps with hand use, dressing, feeding, play, and other daily tasks. Some may find it also helps with posture, adaptive equipment, and ways to make school or home activities easier.
Speech and language therapy can support communication, understanding, and social interaction. If early symptoms of Tmem165-cdg include feeding or swallowing trouble, the same team may also help with mouth control and safer eating.
Dietitians and feeding specialists can help if growth is slow or meals are difficult and tiring. Supportive therapies can include texture changes, high-calorie meal planning, and practical strategies to reduce choking or poor intake.
Your genes may have an impact on how drugs work for you
For people living with TMEM165-CDG, there are no well-established, routine gene-based rules that predict how common medicines will work, so genetic testing is not usually used to choose day-to-day treatment for this condition. Even so, many with TMEM165-CDG can react differently to medicines because the condition may affect the liver, growth, nutrition, or other body systems that help process drugs, so a dose that fits one person may be too much or too little for someone else. In real life, this means doctors often start carefully, watch closely for side effects or benefit, and adjust treatment over time rather than relying on a single genetic result.
Pharmacological treatments
For many living with TMEM165-CDG, medicines are used to manage day-to-day problems rather than treat the underlying genetic cause. At this time, there is no approved disease-specific drug that corrects TMEM165-CDG itself. Drug treatments are not about fixing everything at once, but about easing symptoms such as seizures, constipation, reflux, pain, or low bone strength when these occur. The best treatment for TMEM165-CDG depends on the person's symptoms, age, and overall health.
There is currently no approved medicine that reverses or cures TMEM165-CDG. Care usually focuses on symptom control and close follow-up with specialists.
If seizures are part of TMEM165-CDG, doctors may use anti-seizure drugs such as levetiracetam, valproate, or clobazam. The choice depends on seizure type, age, other health issues, and how well the medicine is tolerated.
For troublesome acid reflux, medicines such as omeprazole or lansoprazole may be used to reduce stomach acid. Some children may also be given famotidine, especially when feeding is uncomfortable or sleep is disrupted by reflux.
Constipation is often treated with medicines like polyethylene glycol or lactulose to soften stools and make bowel movements easier. If needed, doctors may add senna or glycerin suppositories for short-term help.
Genetic influences
For families living with Tmem165-cdg, a common question is why it happened and whether it could happen again. Tmem165-cdg is caused by harmful changes in both copies of the TMEM165 gene, so the genetic cause of this condition is established. It follows an autosomal recessive inheritance pattern, which means each parent usually carries one changed copy without being affected; a carrier means you hold the gene change but may not show symptoms. TMEM165 helps cells process proteins properly, and when the gene is not working well, that process is disrupted throughout the body. The way Tmem165-cdg shows up can differ from one child to another, even within the same family. Genetic testing for Tmem165-cdg can confirm the diagnosis and help families understand the chances of it happening again in a future pregnancy.
Is Tmem165-cdg genetic?
Genetics are central to Tmem165-cdg. It is caused by changes in both copies of the TMEM165 gene, usually inherited from two carrier parents, so genetic testing is key for diagnosis and family planning.
Having a genetic risk is not necessarily a diagnosis
Genetic variants are a normal part of being human and are common in the general population. Most of these variants do not directly affect health and are simply part of natural human diversity. For many genes, having a variant linked to a condition suggests a possible association rather than a certain diagnosis, especially when several genes and environmental factors play a role. In some situations, though, one well-characterized variant in a specific gene can be enough to confirm a diagnosis.
Pharmacogenetics—how genetics influence drug effects
When early symptoms of TMEM165-CDG lead to genetic testing, the result can do more than confirm the diagnosis; it can also help doctors plan care around the body systems most likely to need support, such as growth, liver health, bones, and development. Genetics is only one factor, but in TMEM165-CDG the TMEM165 change is especially important because it affects how cells handle manganese, a trace mineral needed for normal protein processing. Because of that, some specialists may consider a carefully monitored trial of manganese supplementation in selected people with TMEM165-CDG, although the evidence is still limited and this is not a standard treatment for everyone. There are no widely accepted gene-based dosing rules for most routine medicines used in TMEM165-CDG, so treatment usually centers on symptom relief, nutrition, therapies, and regular follow-up rather than a single gene-targeted drug. The genetic result may also give some clues about likely severity, but many living with TMEM165-CDG can still have different symptoms and different treatment needs. Since too much manganese can be harmful, any supplement or medication plan should be supervised closely by a metabolic or genetics specialist.
Interactions with other conditions
For many living with Tmem165-cdg, the bigger day-to-day challenge is often not a direct link to another separate disease, but how this rare genetic condition can overlap with problems involving growth, bones, the liver, digestion, and hormone balance. Doctors call it a “comorbidity” when two conditions occur together, and in Tmem165-cdg this can matter because low bone strength, poor growth, or liver problems may need care from different specialists at the same time. Someone might notice that feeding difficulties or low energy become harder to manage during a stomach bug or another short-term illness, even though this is not unique to Tmem165-cdg. Early symptoms of Tmem165-cdg can also resemble other inherited metabolic or glycosylation disorders, so doctors may need careful testing to sort out what is causing which symptom. Interactions can look very different from person to person, but coordinated follow-up is important so treatments for bone, liver, nutrition, or hormone issues work well together.
How genes can cause diseases
Humans have more than 20,000 genes, each carrying out one or a few specific functions in the body. One gene instructs the body to digest lactose from milk, another tells the body how to build strong bones and another prevents the body's cells from beginning to multiply uncontrollably and developing into cancer. As all of these genes combined are the building instructions for our body, a defect in one of these genes can have severe health consequences.
Through decades of genetic research, we know the genetic code of any healthy/functional human gene. We have also identified that in certain positions on a gene, some individuals may have a different genetic letter from the one you have. We call these hotspots "Genetic Variations" or "Variants" in short. In many cases, studies have been able to show that having the genetic letter "G" in the position makes you healthy, but having the letter "A" in the same position disrupts the gene function and causes a disease. Genopedia allows you to view these variants in genes and summarizes all that we know from scientific research, which genetic letters (Genotype) have good or bad consequences on your health or on your traits.
What other conditions can cause similar symptoms to Tmem165-cdg?
Because TMEM165-CDG can affect growth, learning and development, the liver, and the bones, it can be mistaken for other congenital disorders of glycosylation, a group of rare conditions where the body has trouble attaching sugar parts to proteins. Doctors may also consider inherited bone disorders that cause short stature or unusual bone changes, as well as some metabolic conditions that can lead to poor growth, low muscle tone, or developmental delay. Since the signs can overlap, careful blood tests, scans, and genetic testing are often needed to tell these conditions apart.
History
For families living with Tmem165-cdg, the story has often started with many separate health concerns rather than one obvious diagnosis. A baby might have slow growth, feeding trouble, low muscle tone, or delays in sitting and walking, while blood tests or scans point to problems in more than one body system. It can take time for doctors to see that these pieces belong together.
Tmem165-cdg came to light as doctors learned more about congenital disorders of glycosylation, a group of conditions that affect the way the body modifies and handles many proteins. In recent decades, awareness has grown as improved laboratory testing made it easier to recognize unusual glycosylation patterns in children with complex symptoms. This helped specialists separate Tmem165-cdg from other conditions that can look similar at first, especially in children with developmental concerns, growth problems, and bone or liver findings.
As medical science evolved, researchers linked this condition to a change in a gene involved in the cell’s internal processing system, which gave families and clinicians a clearer explanation for what they were seeing. That shift mattered in everyday care: instead of treating each issue as unrelated, care teams could better understand why a child might need support from several specialists at once. Over time, reports from more affected families showed that Tmem165-cdg can vary from one person to another, with some having more severe symptoms and others a milder course.
Today, Tmem165-cdg is still considered very rare, and much of what is known has come from carefully described case reports and international research collaboration. Even so, the history of this condition reflects a broader change in medicine: children once labeled only by their symptoms can now be recognized as having a specific disorder. Knowing this background can help explain why early symptoms of Tmem165-cdg may seem hard to connect at first, and why diagnosis sometimes depends on both specialist testing and time.