Overview of Rare Diseases
Rare disease is a collective term for a group of diseases that have a very low incidence and are clinically rare. They may manifest as muscle weakness, developmental delays, congenital malformations, enlarged lymph nodes, skin thickening, and fibrosis, etc. The cause of the disease is unclear, and it is generally believed to be related to genetics, the environment, and other factors.
Definition
Rare diseases refer to a group of diseases with extremely low incidence and clinical rarity. The World Health Organization (WHO) defines rare diseases as those diseases with a prevalence of 0.65‰ to 1‰ of the total population, i.e., about 6.5 to 10 per 10,000 people. Rare diseases are usually complex, can involve multiple systems and organs, the course of the disease is often chronic and progressive, and the vast majority of them are hereditary diseases [1-2].
Due to the wide variety of rare diseases, this article only introduces some of them, including spinal muscular atrophy, phenylketonuria, Fanconi anemia, amyotrophic lateral sclerosis, Castleman disease, and systemic sclerosis. See the related entries for more details.
Morbidity
Current research has identified about 6,000 to 8,000 rare diseases, and patients with rare diseases account for about 6% to 8% of the total population worldwide [3].
The World Health Organization estimates that the total number of rare diseases in China is about 20 million [1,3].
About 50% of patients with rare diseases develop the disease at birth or during childhood, and about 30% of affected children do not live beyond the age of 5 years [4].
Etiology
It is currently believed that rare diseases are mainly associated with genetic factors, but may also be related to environmental factors, among others.
Causes of disease
Genetic factors
The occurrence of rare diseases is often related to genetic factors, such as gene mutations, gene deletions, chromosomal abnormalities and so on.
For example, the occurrence of spinal muscular atrophy is associated with mutations in some of the housekeeping genes (i.e., genes that are expressed in all cells under normal or pathological conditions) located on autosomal chromosome 5, and ultimately affects the function of motor neurons [5].
For example, the development of Fanconi anemia may be associated with chromosomal abnormalities, as well as factors such as DNA damage and repair disorders due to gene mutations or gene deletions [6].
Environmental factors
Studies have concluded that people who are chronically exposed to chemicals (e.g., polyvinyl chloride, organic solvents, etc.), or who have been in heavy metal environments such as coal and gold mines for a long period of time, have an increased risk of developing rare diseases such as systemic sclerosis, amyotrophic lateral sclerosis, and other rare diseases [7-8].
Predisposing factors
Infectious factors may be predisposing factors for rare diseases.
Common viral infections such as human cytomegalovirus, EBV, or human immunodeficiency virus, human endogenous retrovirus, and human herpesvirus type 8 infections may predispose to rare diseases such as systemic sclerosis, amyotrophic lateral sclerosis, and Castleman’s disease, for example, through cross-reactivity of viral antigens with self-antigens [9-10].
Predisposing factors
All of the following factors are strongly associated with an increased risk of developing rare diseases and are predisposing factors for rare diseases.
Family members with rare diseases such as spinal muscular atrophy, amyotrophic lateral sclerosis, and Castleman’s disease.
People with relevant occupational exposures (e.g., polyvinyl chloride, organic solvents, heavy metal environments such as coal or gold mines).
Symptoms
Rare diseases are characterized by a variety of disease types, often involving multiple systems and organs. Different disease types and pathogenic mechanisms result in clinical manifestations that often vary greatly among patients with different rare diseases.
Here, we will only briefly introduce spinal muscular atrophy, phenylketonuria, Fanconi anemia, amyotrophic lateral sclerosis, Castleman’s disease and systemic sclerosis.
Main Symptoms
Spinal Muscular Atrophy
Muscle symptoms are the main clinical manifestations of spinal muscular atrophy, which may be characterized by muscle weakness, which tends to be symmetrical and progressive, with proximal over distal and lower over upper limbs [11].
Phenylketonuria
Patients often have growth retardation, intellectual development behind the performance, such as growth and development level, IQ is lower than normal people of the same age, and personality abnormalities such as hyperactivity, autism, etc. Some patients may have recurrent seizures, epilepsy [12].
Fanconi anemia
Congenital malformations: patients often present with microcephaly or microphthalmia, skin pigmentation (e.g., coffee-colored flaky patches), skeletal deformities of the upper limbs (e.g., missing or deformed thumbs, hypoplastic first metacarpal, ulnar deformities), scoliosis, and genital malformations, among other clinical manifestations [6].
Progressive bone marrow failure: patients may show anemia manifestations such as pallor, fatigue, dizziness, and symptoms such as fundus hemorrhage, skin purpura, blood in the urine and black stools.
Tumor susceptibility: patients are often complicated with tumors, such as myelodysplastic syndrome, squamous cell carcinoma of the head and neck, esophageal cancer, etc., and develop corresponding clinical symptoms, such as persistent fever, shortness of breath, persistent and unresolved oral ulcers, dysphagia, swelling of the neck, and hoarseness of voice, etc. [6].
Amyotrophic lateral sclerosis
Patients with amyotrophic lateral sclerosis may often present with awkward, weak finger movements on one or both sides, and fibrillation of the muscle bundles in the affected area. When the muscle atrophy of the hands is severe, the hands may be in the shape of eagle claws; some patients may have muscle atrophy of the limbs and abnormal muscle tone [7,13].
Patients may also have the corresponding symptoms of medullary paralysis, such as tongue muscle atrophy, tremor, weakness of tongue extension, dysarthria, and choking on drinking water.
Castleman disease
Some patients with Castleman’s disease may only present with painless lymph node enlargement; some patients may present with fever, night sweats, weight loss, hepatosplenomegaly, and generalized edema in addition to lymph node enlargement [14-15].
Systemic sclerosis
Patients with systemic sclerosis often present with cutaneous and visceral symptoms.
Cutaneous symptoms
In early stages, patients may present with Raynaud’s phenomenon, which is a color change of pale, blue, or flushed skin on the extremities in response to stimuli such as cold or emotion. In the late stage, the skin shows non-indented skin edema, which gradually becomes hard and thick, accompanied by symptoms such as smaller nose tip, atrophy of the nose, and reduced mouth opening [8-9].
Visceral symptoms
Gastrointestinal involvement: symptoms of esophageal involvement are the most common, and patients may present with symptoms such as acid reflux, abdominal pain, dysphagia, and diarrhea.
Lung involvement: chest tightness, shortness of breath after activity, dyspnea and other manifestations may occur.
Heart involvement: chest pain, palpitations, precordial discomfort and other symptoms may occur.
Kidney involvement: symptoms such as proteinuria, hematuria, and hypertension may occur.
Other symptoms
Spinal Muscular Atrophy
Patients with spinal muscular atrophy may also present with symptoms such as cough weakness, dysphagia, reflux, constipation, and hand tremor due to muscle weakness [11].
Phenylketonuria
Patients with phenylketonuria may also present with dry skin, light-colored hair that is yellow or brown in color, and sweat and urine with a specific ratty odor [12].
Fanconi anemia
Male patients with Fanconi anemia may also have reduced sperm counts [6].
Amyotrophic lateral sclerosis
Patients with amyotrophic lateral sclerosis may also present with conscious numbness, limb paralysis, dyspnea, and cardiac arrhythmias [7,13].
Castleman disease
Patients with Castleman’s disease may also present with renal involvement such as proteinuria, hypertension, or symptoms such as dry mouth and dry eyes.
Systemic sclerosis
Patients with systemic sclerosis may also present with neurologic involvement such as facial pain, convulsions, numbness of the limbs, and sensory disturbances [9].
Medical treatment
Department of Medicine
Neurology
The presence of symptoms such as muscle weakness, epilepsy, muscular dystrophy, weakness of tongue extension, dysarthria, tremor of the hands, and numbness of the limbs suggests prompt consultation with the Department of Neurology.
Pediatrics
If a child has symptoms such as growth retardation, backward intellectual development, or personality abnormalities, it is recommended to consult the Department of Pediatrics in a timely manner.
Hematology
For symptoms such as microcephaly or microphthalmos, skeletal deformities of the upper limbs (e.g. missing or deformed thumbs), hemorrhages in the fundus of the eye, purpura of the skin, blood in the urine, black stools, etc., it is recommended to consult the Department of Hematology in a timely manner.
Preparation for medical consultation
Preparation for Consultation: Registration, Preparation of Documents, Frequently Asked Questions
Tips for Consultation
It is recommended to wear loose-fitting clothes to the clinic so as to facilitate physical examination.
For those with skin symptoms, avoid using cosmetics before the consultation to avoid masking the disease.
Record the development and characteristics of the disease for more reference to the doctor.
Children or patients with obvious symptoms such as muscle weakness or limb paralysis are recommended to visit the doctor accompanied by their family members.
Preparation Checklist for Medical Consultation
Symptom list
Particular attention should be paid to the time of symptom onset, special manifestations, etc.
Are there any manifestations of muscle weakness, cough weakness, difficulty in swallowing, hand tremor, etc.? When did the symptoms start?
Are there any signs of growth retardation, mental retardation, personality abnormalities, light-colored hair, ratty-smelling sweat or urine, etc.? Since when?
Are there any microcephaly or microphthalmos, skeletal deformities of the upper limbs (e.g., missing or deformed thumbs), hemorrhages under the eyes, skin purpura, persistent fever, etc.?
Are there any symptoms such as awkward finger movement, muscle atrophy, weakness of tongue extension, slurred speech, or paralysis of limbs?
Are there any symptoms such as enlarged lymph nodes, fever, generalized edema, hypertension, dry mouth, dry eyes, etc.?
Are there any symptoms such as Raynaud’s phenomenon, reduced nasal tip, nasal atrophy, dysphagia, proteinuria, sensory disturbances?
List of medical history
Is there any long-term employment with exposure to substances such as polyvinyl chloride, organic solvents, coal or gold mining?
Is there a family history of rare diseases such as spinal muscular atrophy, amyotrophic lateral sclerosis, Castleman’s disease, etc.?
Any previous infection with human cytomegalovirus, EBV, human immunodeficiency virus, human endogenous retrovirus, human herpesvirus type 8, etc.?
Checklist
Test results in the last six months, which can be brought to the doctor’s office
Laboratory tests: routine blood test, routine urine test, routine stool test, blood biochemistry, blood phenylalanine test, autoantibody test, etc.
Imaging examination: ultrasonography, CT examination, etc.
Other tests: genetic test, electromyography, muscle biopsy, lymph node biopsy, bone marrow examination, esophageal barium meal, etc.
Medication list
Medication used in the last 3 months, if available in a box or package, bring it to the doctor’s office
Antisense oligonucleotide drugs: sodium nociceptin, etc.
Small molecule correction drugs: risperidone, etc.
Neutral amino acids: glutamic acid, cysteine, etc.
Tetrahydrobiopterin: sapropterin, etc.
Anti-tumor drugs: vincristine, doxorubicin, fludarabine, etc.
Glucocorticoid: prednisone, methylprednisolone, etc.
Immunosuppressants: leflunomide, azathioprine, etc.
Diagnosis
Diagnostic basis
Rare diseases have their own special clinical manifestations and diagnostic manifestations, but as a class of diseases, rare diseases also have certain common features, and currently the diagnosis is mainly based on the history, clinical manifestations, laboratory tests, imaging tests and so on.
Medical history
The following is not necessary for the diagnosis of the disease, but if the following conditions exist, it can provide some reference significance for the diagnosis of the disease.
Has worked for a long period of time with exposure to substances such as polyvinyl chloride, organic solvents, coal or gold mines.
There is a family history of rare diseases such as spinal muscular atrophy, amyotrophic lateral sclerosis, and Castleman’s disease.
History of human cytomegalovirus, EBV, human immunodeficiency virus, human endogenous retrovirus, and human herpesvirus type 8 infections.
Clinical manifestations
Patients may present with muscle weakness, muscle atrophy, dysphagia, weakness of tongue extension, and limb paralysis.
Growth retardation, backward intellectual development, skeletal deformities of the upper limbs (e.g., missing or deformed thumbs), ratty odor of sweat or urine, and skin purpura are present.
It may present with enlarged lymph nodes, persistent fever, generalized edema, hypertension, and Raynaud’s phenomenon, reduced nasal tip, nasal atrophy, dry mouth, dry eyes, and sensory disturbances.
Laboratory Tests
Blood tests
It can clarify whether there are abnormal changes in white blood cell count, red blood cell count and platelet count in the patient’s body.
When there is a decrease in white blood cell, red blood cell and/or platelet counts, it often suggests the presence of anemia, which has a certain significance in guiding the diagnosis and judgment of the condition of Fanconi anemia, Castleman’s disease or systemic sclerosis [16].
Urine routine
Urine routine is mainly used to clarify whether the patient has proteinuria, hematuria and other conditions.
If abnormalities such as proteinuria and hematuria appear in urine routine, it suggests that there may be impaired renal function, which can assist in the diagnosis.
Stool test
Stool routine is mainly to detect the presence of red blood cells and other components.
If the red blood cell count in the feces is increased and the occult blood is positive, it suggests that there may be bleeding in the digestive system, which can help the doctor clarify the condition and guide the treatment [7].
Blood biochemistry
It can be used to assess liver and kidney function, creatine kinase and other indicators.
If serum aminotransferase is elevated and blood creatinine is elevated, it suggests that there may be liver or kidney damage; if creatine kinase is elevated, it suggests that there may be muscle damage, which is helpful in diagnosing and evaluating organ involvement in patients with rare diseases, as well as guiding treatment.
Blood Phenylalanine Test
It is mainly used to identify the presence of abnormal phenylalanine levels.
If newborns have elevated levels of phenylalanine or are accompanied by an increase in the phenylalanine/tyrosine ratio, it suggests that phenylketonuria may be present, which is important for the diagnosis of the disease [12].
Autoantibody test
Autoantibody testing is performed to assess whether the patient has abnormal levels of autoantibodies.
If the results of autoantibodies (e.g., anti-Scl-70 antibody, anti-filament point antibody, anti-RNA polymerase III, etc.) are positive or the titer is abnormally elevated, it can assist in the diagnosis of systemic sclerosis and guide the treatment [17].
Imaging
Ultrasonography
Ultrasonography is mainly used to clarify the presence of manifestations of cardiac involvement.
If cardiac ultrasound shows the presence of a large amount of pericardial effusion, peak tricuspid flow velocity >3.4m/s, etc., it suggests the presence of pericardial effusion, etc., which is of great auxiliary significance to the diagnosis and treatment of the disease.
CT examination
CT examination is often used to clarify whether the patient is combined with lung infection and whether there is tumor occupation and other manifestations.
If there is thickening, increase of lung texture, shadow, etc. in CT examination, it suggests the existence of lung infection; if there is abnormal occupation in esophagus and lungs, it suggests the possibility of combining with tumor, which is helpful for the diagnosis of rare diseases and the evaluation of their conditions.
Other Tests
Genetic test
This test is mainly used for the presence of gene mutation, gene deletion and other abnormalities.
If the results of phenylalanine hydroxylase gene and tetrahydrobiopterin synthetase gene are abnormal, it suggests the possibility of phenylketonuria; if the results of Fanconi anemia complementary group (FANC) related genes, such as FANCC and FANCG, are abnormal, it suggests the possibility of Fanconi anemia, which is of guiding significance in the diagnosis of rare diseases [18].
Electromyography
Electromyography can be used to assess whether the physiologic functions of muscles and neuromuscular junctions are normal.
If EMG shows neurogenic changes, spinal amyotrophy may be present; if it shows loss of innervation and chronic nerve regeneration innervation in different parts of the medulla oblongata, cervical and thoracic regions, amyotrophic lateral sclerosis may be present, which is important for the diagnosis of rare diseases [5].
Muscle biopsy
Muscle biopsy can be used to clarify the nature of the muscle lesion.
If the muscle biopsy shows hypertrophy of muscle fibers or the presence of clusters of muscle fiber atrophy, it suggests the possible presence of spinal muscular atrophy; if the results show neurogenic muscle atrophy, amyotrophic lateral sclerosis may be present, which is important for the diagnosis and treatment of the disease [12].
Lymph node biopsy
Lymph node biopsy is mainly used to clarify the nature of enlarged lymph nodes.
If a lymph node biopsy reveals the presence of enlarged lymphoid follicle-like structures within the lymph node with several small blood vessels penetrating the follicles or Russell’s bodies, it suggests the possibility of Castleman’s disease, which may assist in the diagnosis [15].
Bone marrow examination
Bone marrow examination is commonly used to clarify the hematopoietic cells within the bone marrow.
If the bone marrow examination shows hypoproliferative hypoplasia and megakaryocytopenia, it suggests the possible presence of Fanconi anemia, which is significant in the diagnosis of the disease [6].
Barium esophageal meal
Barium esophageal meal can be used to clarify whether the patient has impaired esophageal function or occupancy.
If the barium esophageal meal shows that the esophageal peristalsis is weakened, disappeared, and the whole esophagus is dilated or stiff, it suggests the existence of impaired esophageal function; if it shows that the esophageal lumen is narrowed, filling defects and other manifestations, it suggests that there may be an abnormal space occupation, which can assist in the diagnosis and guide the treatment [16].
Differential diagnosis
Since rare diseases are a diverse group of diseases with various clinical manifestations, only the differential diagnosis of common rare diseases such as spinal muscular atrophy, Fanconi anemia, and systemic sclerosis will be introduced here.
Congenital muscular dystrophy
Similarities: Both congenital muscular dystrophy and spinal muscular atrophy may present with symptoms such as muscle weakness and hypotonia.
Differences: patients with congenital muscular dystrophy are often accompanied by hip dislocation, proximal joint contracture, strabismus, etc. Some patients may be accompanied by mental retardation; laboratory tests may show a significant increase in creatine kinase, and muscle biopsy may show mild myopathic changes or myotonic dystrophy-like changes [12].
Aplastic anemia
Similarities: Patients with aplastic anemia and Fanconi anemia may present with fever and bleeding.
Differences: patients with aplastic anemia are not associated with congenital malformations, mental retardation, or obvious tumor susceptibility; laboratory tests usually do not show genetic abnormalities such as FANCC and FANCG.
Eosinophilic fasciitis
Similarities: Patients with eosinophilic fasciitis and systemic sclerosis may have symptoms such as swelling, tightness and hardening of the skin of the extremities.
Differences: Eosinophilic fasciitis usually develops after strenuous activities, the skin can be pinched up, there is no Raynaud’s phenomenon, and there is no damage to internal organs. Laboratory tests do not show positive changes of autoantigens such as anti-Scl-70 antibody and anti-binding point antibody, while blood routine often shows an increase in eosinophil count [9].
Treatment
Aim of treatment: early detection and early treatment, relief of symptoms, control of disease progression, etc.
Treatment principle: Because rare diseases are a large group of diseases, the etiology and condition of specific diseases are different, therefore, in the clinic, while actively adopting drugs for treatment, it is also necessary to cooperate with other treatment modes.
Drug therapy
Since rare diseases are a large group of diseases, drug treatment is mainly used to alleviate clinical symptoms and control the development of the disease.
Here, we will only introduce drug therapy for rare diseases such as spinal muscular atrophy, phenylketonuria, Fanconi anemia, Castleman’s disease, and systemic sclerosis.
Antisense oligonucleotide drugs
Commonly used drugs such as nociceptin sodium.
This class of drugs can act against disease-causing target genes or disease-causing target mRNAs to regulate the expression of disease-causing genes from the root cause, and is commonly used in the treatment of rare diseases such as spinal muscular atrophy [19].
Adverse effects such as thrombocytopenia, coagulation abnormalities, and nephrotoxicity may be observed with the use of this class of drugs.
Small molecule modifying drugs
Commonly used drugs such as risperidone.
This class of drugs can be used to treat spinal muscular atrophy by increasing the level of functional motor neuron proteins in patients [20].
The main adverse effects of this class of drugs have been found to include fever, headache, and diarrhea.
Neutral amino acids
Commonly used drugs such as glutamic acid and cysteine.
This class of neutral amino acids can compete with phenylalanine for amino acid transporters at the blood-brain barrier, improving the damage caused by phenylalanine when it enters the brain, and is commonly used in the treatment of patients with phenylketonuria [12].
Large amounts of this class of drugs may lead to adverse effects such as alkalosis and hypokalemia, and are generally contraindicated in patients with renal insufficiency [21].
Tetrahydrobiopterin
Commonly used drugs such as sapropterin.
It can be used to replenish tetrahydrobiopterin in patients with phenylketonuria.
Adverse effects such as headache, runny nose, nasal congestion, diarrhea, and hypophenylalaninemia may occur with this class of drugs [21].
Anti-tumor drugs
Commonly used drugs such as vincristine, doxorubicin, and fludarabine.
These drugs can kill or inhibit the proliferation of tumor cells, affect nucleic acid synthesis, and damage the structure of DNA molecules, etc., and can be used in the treatment of patients with rare diseases such as Fanconi anemia and Castleman disease [21].
Adverse effects of antitumor drugs include nausea, alopecia, fever, myelosuppression, numbness of the limbs and other neurological toxicities.
Glucocorticoids.
Commonly used drugs such as prednisone and methylprednisolone.
They have powerful anti-inflammatory and immunosuppressive effects, and are suitable for relieving the treatment of patients with systemic sclerosis who present with pericarditis, myocardial damage, and inflammatory phase of interstitial lung changes.
Patients who apply glucocorticoids for a long period of time may develop side effects such as infection, osteoporosis, drug-induced diabetes mellitus, and in severe cases, aseptic necrosis of the femoral head [21].
Immunosuppressants.
Commonly used drugs such as leflunomide and azathioprine.
By inhibiting intracellular dihydrofolate reductase, they play a role in improving and delaying the progression of the disease, which can reduce the dosage of glucocorticoid drugs, and are suitable for the treatment of patients with systemic sclerosis who have combined gastrointestinal, pulmonary, cardiac and other internal organ involvement.
Common adverse effects of this class of drugs include diarrhea, nausea, ulcerative stomatitis, dermatitis, alopecia, hepatic damage and interstitial inflammation of the lungs, etc., and should be used with caution in patients with hepatic and renal insufficiency [21].
Other treatments
There are a wide variety of rare diseases, and along with medication, other treatment modalities such as assisted respiration, enteral nutrition, blood transfusion therapy, and rehabilitation training can help to alleviate symptoms and improve the condition.
Here, only other treatment modalities for patients with rare diseases such as spinal muscular atrophy, amyotrophic lateral sclerosis, Fanconi anemia, and systemic sclerosis are described.
Assisted Breathing
Patients with spinal amyotrophy and amyotrophic lateral sclerosis require ventilator-assisted respiration if necessary, and prompt suctioning to prevent aspiration.
Enteral nutrition
Patients with rare diseases such as spinal muscular atrophy and amyotrophic lateral sclerosis are unable to eat on their own, so enteral nutrition, such as nasogastric tubes, can be used for a short period of time to help replenish nutrients.
Blood Transfusion Therapy
Patients with rare diseases such as Fanconi anemia may be treated with blood transfusion as prescribed by the doctor if they have severe symptoms of anemia and bleeding.
Rehabilitation
Patients with rare diseases such as amyotrophic lateral sclerosis who have obvious joint ankylosis or contracture can undergo appropriate rehabilitation training such as joint mobility training and reverse muscle exercise to help improve their quality of life.
Dialysis treatment
Systemic sclerosis patients with acute malignant hypertension, acute renal failure and other renal crises can be treated with hemodialysis or peritoneal dialysis when the condition is serious.
Prognosis
Cure
Rare diseases are a large group of diseases with diverse etiologies and different clinical manifestations, and therefore the prognosis varies greatly from one disease to another. Here, we will only describe the prognosis of spinal muscular atrophy, phenylketonuria, Fanconi anemia, amyotrophic lateral sclerosis, Castleman’s disease, and systemic sclerosis.
Spinal Muscular Atrophy
Patients with spinal muscular atrophy who have an early onset of the disease (generally defined as earlier than 18 months after birth) have a poor prognosis and a high mortality rate.
Patients with later onset of the disease can be managed with effective treatment, reducing the impact on life expectancy and quality of life.
Phenylketonuria
Children with phenylketonuria usually have a better prognosis if early intervention and treatment are effective in controlling the disease without significant growth and intellectual impairment.
Fanconi anemia
Patients with Fanconi anemia who develop bone marrow failure, tumors, etc. are usually difficult to cure and have a poor prognosis.
Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis is usually poorly treated, has a poor prognosis, and patients tend to die due to respiratory muscle paralysis, lung infections, and other factors [12].
Castleman’s disease
Patients with Castleman disease who have focal lesions usually have a good prognosis with effective treatment.
In the presence of renal involvement and hypergammaglobulinemia, patients are prone to malignancy and tend to have a poorer prognosis.
Systemic sclerosis
Patients with systemic sclerosis can be controlled and have a better prognosis if they are treated early and effectively.
Some patients with systemic sclerosis combined with internal organ function damage have rapid progression of disease and poorer prognosis.
Prognostic factors
Rare diseases are a large group of diseases whose prognosis is affected by many factors. The following are examples of rare diseases such as spinal muscular atrophy, Fanconi anemia, amyotrophic lateral sclerosis, and Castleman’s disease that may lead to a poor prognosis.
Patients with spinal muscular atrophy whose age of onset is earlier than 18 months after birth.
Patients with Fanconi anemia in combination with bone marrow failure, tumors, and other conditions.
Patients with amyotrophic lateral sclerosis who have respiratory muscle paralysis, lung infection, etc.
Patients with Castleman’s disease who have renal involvement, hypergammaglobulinemia, etc.
Patients with systemic sclerosis who have a combination of renal, pulmonary hypertension, and cardiac involvement.
Daily
Daily Management
Dietary management
Take care of balanced nutrition, consume more high quality protein such as meat, milk, etc., and vitamin-rich food such as vegetables and animal liver.
Avoid raw and cold food to avoid gastrointestinal infections.
For patients with rare diseases who have difficulty in eating, they should consume soft and liquid food and eat small and frequent meals.
Children with phenylketonuria under 1 year of age should consume special medical formula without phenylalanine; children over 1 year of age and adult patients should minimize the intake of phenylalanine-rich foods, such as meats, cheeses and nuts.
Life management
Pay attention to personal hygiene, clean and disinfect the living environment regularly, open windows more often for ventilation, and actively prevent infection.
Appropriate exercise can be carried out as prescribed by the doctor, pay attention to moving joints, but should avoid strenuous exercise and bumps.
Psychological support
The course of rare diseases is generally long and recurrent, and patients may suffer from anxiety, depression and other adverse emotions.
If the patient is emotionally unstable or psychologically depressed, relatives and friends can increase their company and provide psychological intervention if necessary.
Disease monitoring
Monitor body temperature and record it daily.
Observe whether there is any infection, such as cough, sputum, diarrhea.
Observe whether there is any change in the degree of illness, such as worsening of muscle weakness, hemorrhage under the eyes, skin purpura or black stools, dysphagia, shortness of breath after activity, etc. Seek medical advice promptly if persistent fever and respiratory distress occur.
In case of intolerable adverse effects (e.g. bone marrow suppression, severe infection), timely follow-up is required.
Follow-up
As rare diseases have a long course and are recurrent, regular follow-up can help relieve symptoms and prevent or delay the onset of internal organ damage.
Different patients with rare diseases have different clinical manifestations and need to be followed up regularly according to the doctor’s instructions, usually within one to two months.
Patients need to have regular blood tests, blood biochemistry, CT scan, electromyography, etc. according to their condition.
Prevention
The causes of rare diseases are complex and varied, and it is generally difficult to prevent them effectively. However, the following healthy lifestyles or behaviors, etc. can help reduce the risk of developing the disease.
Pay strict attention to personal hygiene and maintain a regular routine.
Avoiding long-term work that involves exposure to substances such as polyvinyl chloride, organic solvents, coal or gold mining.
People with a family history of rare diseases such as spinal muscular atrophy, amyotrophic lateral sclerosis, Fanconi anemia, and phenylketonuria should undergo genetic counseling before marriage and pregnancy, and prenatal diagnosis during pregnancy; and newborns should be screened promptly.