Alpha-mannosidosis, infantile form is a rare genetic condition that affects how the body breaks down certain sugars. Babies with this condition often have frequent infections, weak muscle tone, feeding difficulties, and delays in development. Features can include enlarged liver and spleen, hearing loss, distinctive facial traits, and skeletal changes that doctors may notice in infancy. The condition is lifelong and can be severe, and early symptoms of Alpha-mannosidosis often progress without treatment. Care focuses on infection prevention, supportive therapies, and in some cases bone marrow or stem cell transplant, which may improve outcomes but does not cure the condition.
Overview
Alpha-mannosidosis, infantile formSymptoms
In the infantile form of Alpha-mannosidosis, signs usually appear in early infancy. Babies often have frequent infections, weak muscle tone, developmental delay, and hearing loss, with coarse facial features, enlarged liver or spleen, and skeletal changes.
Outlook and prognosis
Outlook for infantile Alpha-mannosidosis varies. Early symptoms of Alpha-mannosidosis often include frequent infections, delayed development, and hearing loss; starting multidisciplinary care early can slow complications and support learning and mobility. Many need ongoing therapies, and some benefit from stem cell transplant.
Causes and risk factors
Alpha-mannosidosis, infantile form is caused by mutations in the MAN2B1 gene, inherited in an autosomal recessive pattern. Risk is higher when both parents are carriers, with consanguinity or an affected child. Infections can influence severity but do not cause it.
Genetic influences
Genetics fully determine Alpha‑mannosidosis, infantile form; it results from inherited changes in the MAN2B1 gene. It follows an autosomal recessive pattern, so both parents typically carry one variant. Different variants can influence severity and early symptoms.
Diagnosis
Doctors suspect infantile Alpha-mannosidosis from early features and exam. Confirmation uses low alpha‑mannosidase activity on blood tests and MAN2B1 genetic testing; imaging and urine oligosaccharide analysis may support the genetic diagnosis of Alpha‑mannosidosis.
Treatment and drugs
Treatment for alpha‑mannosidosis, infantile form focuses on enzyme replacement therapy and, in selected cases, stem cell transplantation to slow disease progression. Supportive care—hearing aids, seizure control, physical and speech therapy—helps daily function. Regular specialist follow‑up guides nutrition, infections, and orthopedic needs.
Symptoms
In the infantile form, early signs often appear in the first year, affecting growth, development, and infection resistance. Parents may notice early features of Alpha-mannosidosis, infantile form like frequent infections, delays in sitting or talking, and changes in facial features. Features vary from person to person and can change over time. These signs reflect how the condition affects many body systems, including the immune system, hearing, and bones.
Children often reach milestones later, like sitting, crawling, or walking. Thinking and learning skills tend to progress more slowly over time.
Frequent ear, chest, or sinus infections are common due to a weaker immune response in Alpha-mannosidosis, infantile form. Illnesses may last longer and require more doctor visits or antibiotics.
Hearing can be reduced from inner ear involvement and repeated ear infections in Alpha-mannosidosis. This can make responding to sounds or learning words harder.
Babbling, first words, and sentences often arrive later than expected. Speech may sound nasal or unclear, and expressive language can lag behind understanding.
How people usually first notice Alpha-mannosidosis, infantile form?
Many families first notice something is different in the first months of life: frequent respiratory or ear infections, feeding difficulties, and a baby who seems unusually floppy (low muscle tone) or slow to meet early motor milestones. As the first year unfolds, doctors may pick up the first signs of Alpha‑mannosidosis on exam—coarse facial features, enlarged liver or spleen, fluid in the middle ear with hearing loss, and developmental delays—which often prompt referral for metabolic testing. In many cases, the condition is confirmed in early infancy through enzyme testing and genetic analysis after these early red flags raise concern about how Alpha‑mannosidosis is first noticed.
Types of Alpha-mannosidosis, infantile form
Alpha‑mannosidosis is a genetic condition with several clinical variants that differ mainly by age of onset and how quickly symptoms progress. The infantile form tends to appear early and move faster, often affecting development, the immune system, and hearing. People may notice different sets of symptoms depending on their situation. When talking about types of Alpha‑mannosidosis, most clinicians use recognized clinical subtypes based on timing and severity rather than different genes, so “types of Alpha‑mannosidosis” usually means infantile, juvenile, or adult/attenuated forms.
Infantile severe
Symptoms start in the first year or two with frequent infections, large tongue, hernias, and early developmental delays. Hearing loss and skeletal changes often show up early, and growth may be slower than peers. Without treatment, symptoms can progress quickly.
Juvenile moderate
Signs appear later in early childhood with learning challenges, speech delay, and recurrent ear or sinus infections. Hearing loss and joint stiffness may become more noticeable over time. The course is slower than the infantile form but can still be progressive.
Adult attenuated
Symptoms tend to be milder and show up in later childhood or adulthood, often with balance issues, joint problems, and hearing loss. Learning difficulties may be present but less severe, and infections usually decrease with age. Progression is typically slow, with wide variation in day‑to‑day impact.
What genetics can tell you about symptoms
In infantile alpha‑mannosidosis, harmful changes in the MAN2B1 gene severely reduce the alpha‑mannosidase enzyme, leading to early symptoms like frequent infections, enlarged liver and spleen, hearing loss, and developmental delay. More disruptive variants often bring earlier onset and faster progression.
Causes and risk factors
The infantile form is caused by changes in the MAN2B1 gene that sharply lower the alpha-mannosidase enzyme and drive very early, severe disease. It is inherited in an autosomal recessive pattern, so a child is affected when both parents carry the same gene change. Risk is higher with a family history or when parents are related by blood, and genetic testing may be offered when early symptoms of Alpha-mannosidosis, infantile form raise concern. Some risks are modifiable (things you can change), others are non-modifiable (things you can’t). Infections, poor nutrition, and missed vaccinations do not cause Alpha-mannosidosis, infantile form but can worsen health and increase complications.
Environmental and biological risk factors
Families often wonder what, if anything, in pregnancy or the environment could change the chances of Alpha-mannosidosis, infantile form. Researchers are still exploring how outside influences interact with our inner biology. So far, studies have not shown clear environmental or pregnancy-related factors that raise the likelihood before any early symptoms appear. In short, outside exposures have not been found to drive whether this condition occurs.
Current research has not identified specific prenatal or early-life exposures that increase the chance of Alpha-mannosidosis, infantile form. Typical exposures like air pollution, common infections, or household chemicals have not been shown to cause it. Evidence to date points away from outside triggers.
For Alpha-mannosidosis, infantile form, advanced maternal or paternal age does not appear to raise the likelihood. This contrasts with some chromosomal conditions where age can be a factor. Available studies have not found a consistent age-related pattern.
Common pregnancy conditions such as diabetes, high blood pressure, or short-term fevers have not been linked to higher risk. These conditions matter for overall pregnancy wellness but do not create this condition. Current data do not show a causal connection.
Radiation, heavy metals such as lead or mercury, and hormone-disrupting chemicals can affect fetal development, but they are not established causes of this condition. Where studied, no clear association has been found. Evidence remains limited but does not support a link.
Genetic risk factors
Alpha-mannosidosis, infantile form is caused by harmful changes in the MAN2B1 gene that severely reduce the alpha-mannosidase enzyme. It follows an autosomal recessive pattern, so symptoms appear when both copies of the gene are affected. Carrying a genetic change doesn’t guarantee the condition will appear; carriers usually have no symptoms but can pass the gene to their children. In the infantile form, very low or near-absent enzyme activity is what drives the early symptoms of alpha-mannosidosis.
MAN2B1 variants: Changes in the MAN2B1 gene cause Alpha-mannosidosis, infantile form by reducing or eliminating the alpha-mannosidase enzyme. Truncating or severely damaging missense variants often lead to little or no enzyme.
Autosomal recessive: The condition appears when both gene copies have disease-causing changes—one inherited from each parent. Each pregnancy between two carriers has a 25% (1 in 4) chance of an affected child.
Enzyme activity level: Very low residual enzyme activity is linked to Alpha-mannosidosis, infantile form with earlier, more severe features. Certain variant combinations lead to near-absent activity, which drives early symptoms and faster progression.
Founder variants: In some regions or families, a single ancestral (founder) variant is more common, raising the local carrier rate. People with roots from these areas may be more likely to have two carriers in the same family.
Related parents: Parents who are biologically related are more likely to carry the same rare MAN2B1 variant. This increases the chance of a child with Alpha-mannosidosis, infantile form.
Two different variants: Many affected children inherit two different MAN2B1 changes, one from each parent. The specific pair can shape severity and timing, including whether the course is infantile and rapidly progressive.
Lifestyle risk factors
Alpha-mannosidosis, infantile form, is a genetic condition present from birth; lifestyle habits do not cause it but can influence symptoms, complications, and quality of life. Thoughtful daily routines can support breathing, mobility, nutrition, sleep, and infection prevention. Below are practical ways showing how lifestyle affects Alpha-mannosidosis, infantile form and the lifestyle risk factors for Alpha-mannosidosis, infantile form.
Consistent, energy-dense nutrition supports growth and immune function, which are often challenged in alpha‑mannosidosis. Working with feeding and swallowing strategies can lower aspiration risk and respiratory infections.
Upright positioning, slow pacing, and texture-modified foods can reduce choking and aspiration in children with hypotonia. Fewer aspiration events may mean fewer pneumonias and hospitalizations.
Regular chest physiotherapy and assisted coughing can help mobilize secretions. This may reduce mucus buildup and lower the frequency of respiratory infections common in this condition.
Staying current with routine and specialist-recommended vaccines reduces the risk and severity of infections. Fewer infections can lessen setbacks in breathing, feeding, and overall development.
Risk prevention
Alpha-mannosidosis, infantile form, can’t be fully prevented because it’s a genetic condition present from birth. Care focuses on avoiding complications, catching problems early, and supporting healthy growth as much as possible. Prevention is about lowering risk, not eliminating it completely. Early, coordinated care can make day-to-day life safer and more comfortable.
Ask about early evaluation for stem cell transplant in specialized centers. When done very early, it may slow nerve and body changes linked to infantile alpha-mannosidosis.
In some regions, enzyme replacement may help non-brain symptoms in alpha-mannosidosis. Your care team can explain if and when it fits your child’s needs.
Keep routine vaccines up to date to lower the risk of pneumonia, ear infections, and other illnesses. Annual flu shots and other recommended vaccines can reduce infection-related setbacks in alpha-mannosidosis.
Treat fevers, ear infections, and chest colds promptly to prevent hospital stays. Good handwashing, avoiding sick contacts, and quick medical review for breathing changes help protect children with alpha-mannosidosis.
Transmission
Alpha-mannosidosis, infantile form is not contagious; it cannot be spread by coughing, touch, breastfeeding, or everyday contact. This condition is inherited in an autosomal recessive way: a child is affected only when they receive two nonworking copies of the gene, one from each parent who is a healthy carrier. When both parents are carriers, each pregnancy has a 25% (1 in 4) chance of Alpha-mannosidosis, infantile form, a 50% (1 in 2) chance the child will be a carrier, and a 25% chance of neither. New changes in the gene can occur but are uncommon; most cases reflect how Alpha-mannosidosis, infantile form is inherited within a family.
When to test your genes
Alpha-mannosidosis, infantile form is genetic, so consider testing if there’s developmental delay, recurrent infections, hearing loss, or coarse facial features in infancy, especially with a family history. Early diagnosis guides enzyme therapy, supportive care, and transplant decisions. Test parents and siblings to clarify carrier status and plan future pregnancies.
Diagnosis
Early signs often show up in everyday life—frequent ear or chest infections, slow progress with speech, or trouble gaining skills that other infants pick up sooner. Doctors look for a pattern of features and confirm it with a few focused tests. Getting a diagnosis is often a turning point toward answers and support. Because this condition is present from birth, testing aims to pinpoint it early so care can start promptly.
Providers look for a combination of early developmental delays, frequent infections, enlarged liver or spleen, and distinctive facial features. Together, these clues can suggest Alpha-mannosidosis, infantile form. They guide which tests to order next.
A detailed family and health history can help identify relatives with similar early symptoms or early loss. This context raises the index of suspicion for Alpha-mannosidosis, infantile form. It can also guide which family members might benefit from testing.
A simple urine test checks for certain sugar-rich molecules that build up when alpha-mannosidase is low. High levels support the suspicion of Alpha-mannosidosis, infantile form. Results help prioritize enzyme and genetic tests.
A blood draw or skin sample can measure alpha-mannosidase activity in cells. Very low activity strongly supports the diagnosis of Alpha-mannosidosis, infantile form. This test helps distinguish it from other lysosomal conditions.
Stages of Alpha-mannosidosis, infantile form
Alpha-mannosidosis, infantile form does not have defined progression stages. This form usually starts very early and can worsen quickly, but changes don’t follow set step-by-step stages; instead, severity varies and complications can appear at different times. Different tests may be suggested to help confirm the diagnosis, including enzyme activity checks, genetic testing, hearing exams, and imaging to look at bones or organs. Doctors look at early symptoms of Alpha-mannosidosis, infantile form—such as frequent infections, feeding difficulties, or delayed milestones—together with lab results to monitor how things are changing over time.
Outlook and prognosis
Families often want to know how life will change as Alpha-mannosidosis, infantile form unfolds. Early symptoms of Alpha-mannosidosis in babies often include frequent infections, hearing problems, developmental delay, and coarse facial features, which can progress without treatment. Doctors call this the prognosis—a medical word for likely outcomes. In the infantile form, the condition tends to move quickly, with worsening muscle weakness, problems with balance, and increasing learning and communication challenges over the first years of life.
Everyone’s journey looks a little different. Some children have severe immune problems and recurrent lung infections; others have more pronounced neurological issues such as seizures. Without disease-modifying treatment, serious complications can lead to shortened life expectancy, often in childhood or adolescence, depending on severity and access to supportive care. In medical terms, the long-term outlook is often shaped by both genetics and lifestyle.
Early care can make a real difference. Supportive treatments—prompt antibiotics for infections, hearing support, physical therapy, and careful nutrition—can improve comfort and daily function, even if they don’t stop the disease by themselves. The main therapy that can change the course is hematopoietic stem cell transplantation (HSCT), ideally performed early; studies suggest HSCT may slow neurological decline, reduce infections, and improve survival compared with no transplant, though risks and outcomes vary by center and child. Talk with your doctor about what your personal outlook might look like, including whether HSCT is a reasonable option and how best to manage complications over time.
Long-term effects
Alpha-mannosidosis, infantile form, tends to unfold early and affect many areas of health over time. Families often notice early symptoms of alpha-mannosidosis in the first year, and features usually progress without treatment. Long-term effects vary widely, and the pace can differ from child to child. Overall health and lifespan are shaped by the combined impact of infections, bone and nerve changes, and organ involvement.
Ongoing global developmental delay and intellectual disability are common. Speech often stays very limited, and learning plateaus over time. Daily support needs typically increase as features progress.
Progressive hearing loss is frequent in infantile alpha-mannosidosis. It can move from mild to severe over the years. Communication becomes harder as hearing declines.
Frequent ear, sinus, and chest infections occur due to immune system weakness. Illnesses can be severe and may lead to hospital stays. For some, infection frequency lessens with age but remains a concern.
Stiff joints, spinal curvature, and changes in the ribs and hips can develop. These skeletal features limit mobility and contribute to pain. Walking and fine motor skills often become harder.
How is it to live with Alpha-mannosidosis, infantile form?
Daily life with infantile alpha‑mannosidosis often centers on frequent medical visits, therapies, and support for developmental milestones that come more slowly, like sitting, walking, and talking. Recurrent ear and sinus infections, hearing loss, and fatigue can make school or daycare harder, so days may be planned around medications, hearing aids, speech and physical therapy, and extra rest. Families and caregivers commonly become skilled coordinators—working with genetics, neurology, ENT, and therapy teams—while also adapting the home for safety and communication. For many, community resources, early‑intervention services, and respite care help share the load and protect time for play, connection, and siblings’ needs.
Treatment and drugs
Treatment for alpha-mannosidosis, infantile form focuses on slowing the disease, managing symptoms, and supporting development. The only therapy that can change the course of the condition is a stem cell transplant (hematopoietic stem cell transplantation), ideally early in life, which may improve survival and help preserve hearing, mobility, and learning, though it carries serious risks and requires specialized centers. Supportive care can make a real difference in how you feel day to day, including physical and occupational therapy to maintain movement, speech and feeding support, hearing aids or cochlear implants for hearing loss, and treatment of frequent infections with vaccines, prompt antibiotics, and sometimes immune support. Seizures, if present, are treated with anti-seizure medicines, and orthopedic care may address joint stiffness or spine issues; a doctor may adjust your dose to balance benefits and side effects. Enzyme replacement therapy has been studied for other forms of alpha-mannosidosis but is not established for the infantile form, so your doctor may suggest clinical trial evaluation where available.
Non-drug treatment
Families often focus on day-to-day function—movement, feeding, hearing, and learning—when planning care for the infantile form of alpha-mannosidosis. Alongside medicines, non-drug therapies can support development, comfort, and participation at home and in school. Starting supports early—even before early symptoms of alpha-mannosidosis are obvious—can help protect function and reduce complications over time.
Coordinated services bring therapy into daily routines during the most important developmental window. Teams help set goals, coach caregivers, and track progress.
Gentle exercises help build strength, balance, and joint flexibility. Regular stretching can lower the chance of contractures and reduce pain during growth.
Practice with hand skills and self-care makes dressing, feeding, and play easier. Adaptive tools and seating can improve independence and comfort.
Therapy supports early communication, feeding, and swallowing skills. Augmentative and alternative communication can give a reliable voice when speech is limited.
Your genes may have an impact on how drugs work for you
Even with the same diagnosis, people can process medicines differently because gene variants change how fast the body absorbs, breaks down, or clears a drug. For infantile alpha‑mannosidosis, genetics may influence responses to enzyme replacement, transplant outcomes, dosing, and side‑effect risk.
Pharmacological treatments
Medications for alpha-mannosidosis, infantile form focus on enzyme replacement and easing complications like infections, seizures, reflux, and pain. Velmanase alfa (enzyme replacement therapy) can help some body symptoms, though it does not reliably treat brain involvement. Not everyone responds to the same medication in the same way. Treatment is individualized and often combined with therapies like surgery, nutrition support, or transplant planning when appropriate.
Velmanase alfa (Lamzede) aims to replace the missing enzyme and may improve non‑neurologic issues such as lung and infection burden. Starting it near the time early symptoms of alpha-mannosidosis infantile form appear may offer more benefit outside the brain. It does not cross well into the brain, so effects on learning or development are limited.
Amoxicillin–clavulanate or cefuroxime are commonly used for ear, sinus, or chest infections; azithromycin may be used if penicillin allergy is present. Repeated cultures help tailor choices and reduce resistance. Doctors may use longer courses during severe or recurrent infections.
Intravenous immunoglobulin can be considered when frequent, serious infections occur despite standard care. It supplements antibodies to lower infection frequency and severity. Dosing schedules are individualized and reassessed over time.
Levetiracetam is often a first choice for seizures, with alternatives like valproate or clobazam when needed. Dosing may be increased or lowered gradually to balance seizure control with side effects. Drug levels and liver function are monitored if certain medicines are used.
Genetic influences
Alpha-mannosidosis, infantile form, happens when a child inherits two nonworking copies of the alpha-mannosidase gene (called MAN2B1), which cells use to break down certain sugars. Some conditions are passed down through families (inherited disorders). Parents are usually healthy carriers of one gene change; when both carry it, each pregnancy has a 25% chance of a child with alpha-mannosidosis, a 50% chance of a carrier child, and a 25% chance of a child without the change. The infantile form usually means the enzyme made from this gene is almost absent, so signs begin in the first months and tend to progress quickly. Even so, the exact gene changes can leave different amounts of working enzyme, so severity can vary. Genetic testing of MAN2B1, often paired with an enzyme test, can confirm the diagnosis and help families understand recurrence risk and options.
Is Alpha-mannosidosis, infantile form genetic?
Genetics fully determine Alpha‑mannosidosis, infantile form; it results from inherited changes in the MAN2B1 gene. It follows an autosomal recessive pattern, so both parents typically carry one variant. Different variants can influence severity and early symptoms.
Pharmacogenetics—how genetics influence drug effects
Treatment for Alpha-mannosidosis, infantile form often involves enzyme infusions, close infection care, and in some centers, a stem cell transplant. Changes in the MAN2B1 gene that cause the condition usually don’t change how the enzyme drug is dosed, but they can line up with how severe the condition is and what to expect from treatment. Genes outside MAN2B1 can influence how a child’s body handles medicines used along the way—such as seizure medicines, antibiotics, pain relievers, and especially drugs given before and after transplant; a “slow metabolizer” may process medicine more slowly and be more prone to side effects, while others clear the same dose quickly and may get less benefit. Because of this, teams often monitor drug levels in the blood and adjust dosing to fit the child, particularly for the conditioning chemotherapy before transplant and immune‑suppressing drugs afterward. In some centers, a small genetic test is done ahead of time to guide a safer starting dose for certain medicines and to make side effects less likely. Even with testing, response depends on many factors—age, liver and kidney function, infections, and interactions with other medicines—so genetics is one piece of a larger care plan.
Interactions with other conditions
In the infantile form, frequent infections can pile on top of existing challenges—repeated ear or chest infections may worsen hearing, breathing, and overall energy. Because Alpha-mannosidosis, infantile form involves a weaker immune response, common illnesses like ear and sinus infections or pneumonia can be more frequent and sometimes more severe, and they may trigger setbacks in feeding, sleep, or development. Doctors call it a “comorbidity” when two conditions occur together. When viral illnesses such as influenza, RSV, or COVID-19 are also in the mix, hospital visits may be more likely and recovery can take longer; if allergies or asthma are present, they can add to airway swelling and make breathing symptoms feel heavier. Early symptoms of Alpha-mannosidosis, infantile form can be harder to recognize when another disorder is present—for example, developmental delays may be attributed to prematurity, or hearing problems may be masked by recurrent ear infections. Working with a coordinated team (pediatrics, immunology, ENT, and neurology) helps sort out which condition is driving which symptom and plan care that covers both.
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.
History
Throughout history, people have described babies who struggled to feed, caught infections easily, and later showed delays in sitting, standing, and speaking. Family stories sometimes mentioned a broad forehead, larger tongue, or ears that stuck out a bit—details that, in hindsight, fit what we now recognize as Alpha‑mannosidosis, infantile form. Doctors in the early 20th century recorded infants with frequent ear and chest infections and swollen organs, but without today’s tests, these patterns were often grouped with other childhood conditions.
First described in the medical literature as a storage disorder in the late 1960s and early 1970s, the condition was linked to a missing or poorly working enzyme that normally helps clear certain sugars from cells. Initially understood only through symptoms, later it became clear that different ages of onset existed, and the infantile form marked the most rapidly progressing course. As medical science evolved, pathologists connected the dots: the same build‑up seen under the microscope in several organs matched the clinical picture of repeated infections, developmental delay, and hearing problems in young children.
Advances in genetics in the 1980s and 1990s identified changes in the MAN2B1 gene as the root cause, confirming why the condition appeared in siblings and sometimes across generations. Newborn screening never became routine for Alpha‑mannosidosis, so most infantile cases were recognized only after symptoms led families from one specialist to another. Over time, descriptions became more precise, separating the infantile form from juvenile and adult‑onset presentations, which progress more slowly.
With each decade, care shifted from purely supportive approaches—treating infections and helping with hearing and mobility—to considering disease‑targeted options. Bone marrow and stem cell transplantation were explored to supply the missing enzyme, especially when done early in life. Enzyme replacement therapy entered clinical studies more recently, informed by long‑term natural history data that tracked how quickly infant symptoms can advance without treatment.
Despite evolving definitions, the core story has stayed consistent: in the infantile form of Alpha‑mannosidosis, the earliest symptoms often include recurrent infections, trouble gaining skills on time, and hearing loss. Knowing the condition’s history helps explain why timely recognition matters now more than ever—what was once a puzzling cluster of infant problems is today a clearly defined, testable, and increasingly treatable rare disease.