Amyloid Neuropathies
Amyloid Neuropathies, Familial
Prealbumin
Amyloidosis
Amyloid
Diabetic Neuropathies
Amyloid beta-Peptides
Serum Amyloid A Protein
Peripheral Nervous System Diseases
Amyloid beta-Protein Precursor
Hereditary Sensory and Motor Neuropathy
Islet Amyloid Polypeptide
Cerebral Amyloid Angiopathy
Hereditary Sensory and Autonomic Neuropathies
Optic Neuropathy, Ischemic
Serum Amyloid P-Component
Polyneuropathies
Sural Nerve
Amyloid Precursor Protein Secretases
Alzheimer Disease
Capture of a dimeric intermediate during transthyretin amyloid formation. (1/93)
Point mutations in the human plasma protein transthyretin are associated with the neurological disorder familial amyloidosis with polyneuropathy type 1. The disease is characterized by amyloid fibril deposits causing damage at the site of deposition. Substitution of two amino acids in the hydrophobic core of transthyretin lead to a mutant that was very prone to form amyloid. In addition, this mutant has also been shown to induce a toxic response on a neuroblastoma cell line. Renaturation of the transthyretin mutant at low temperature facilitated the isolation of an amyloid-forming intermediate state having the apparent size of a dimer. Increasing the temperature effectively enhanced the rate of interconversion from a partly denatured protein to mature amyloid. Using circular dichroism the beta-sheet content of the formed mature fibrils was significantly lower than that of the native fold of transthyretin. Morphology studies using electron microscopy also indicated a temperature-dependent transformation from amorphous aggregates toward mature amyloid fibrils. In addition, 1-anilino-8-naphtalenesulfonate fluorescence studies suggested the loss of the thyroxin-binding channel within both the isolated intermediate and the mature fibrils. (+info)Deposition of transthyretin in early stages of familial amyloidotic polyneuropathy: evidence for toxicity of nonfibrillar aggregates. (2/93)
Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of transthyretin (TTR) amyloid fibrils, particularly in the peripheral nervous system. No systematic immunohistochemical data exists relating TTR deposition with FAP progression. We assessed nerves from FAP patients in different stages of disease progression (FAP 0 to FAP 3) for TTR deposition by immunohistochemistry, and for the presence of amyloid fibrils by Congo Red staining. The nature of the deposited material was further studied by electron microscopy. We observed that early in FAP (FAP 0), TTR is already deposited in an aggregated nonfibrillar form, negative by Congo Red staining. This suggested that in vivo, preamyloidogenic forms of TTR exist in the nerve, in a stage before fibril formation. Cytotoxicity of nonfibrillar TTR was assessed in nerves of different FAP stages by immunohistochemistry for macrophage colony-stimulating factor. FAP 0 patients already presented increased axonal expression of macrophage colony-stimulating factor that was maintained in all other stages, in sites related to TTR deposition. Toxicity of synthetic TTR fibrils formed in vitro at physiological pH was studied on a Schwannoma cell line by caspase-3 activation assays and showed that early aggregates but not mature fibrils are toxic to cells. Taken together, these results show that nonfibrillar cytotoxic deposits occur in early stages of FAP. (+info)Myocardial muscarinic receptor upregulation and normal response to isoproterenol in denervated hearts by familial amyloid polyneuropathy. (3/93)
BACKGROUND: Patients with familial amyloid polyneuropathy, a rare hereditary form of amyloidosis, have progressive autonomic neuropathy. The disease usually does not induce heart failure but is associated with sudden death, conduction disturbances, and an increased risk of complications during anesthesia. Although cardiac sympathetic denervation has been clearly demonstrated, the postsynaptic status of the cardiac autonomic nervous system remains unelucidated. METHODS AND RESULTS: Twenty-one patients were studied (age, 39+/-11 years; normal coronary arteries; left ventricular ejection fraction 68+/-9%). To evaluate the density and affinity constants of myocardial muscarinic receptors, PET with (11)C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, was used. Cardiac beta-receptor functional efficiency was studied by the heart rate (HR) response to intravenous infusion of isoproterenol (5 minutes after 2 mg of atropine, 5, 10, and 15 ng/kg per minute during 5 minutes per step). The mean muscarinic receptor density was higher in patients than in control subjects (B'(max), 35.5+/-8.9 versus 26.1+/-6.7 pmol/mL, P=0.003), without change in receptor affinity. The increase in HR after injection of atropine as well as of MQNB was lower in patients compared with control subjects despite a similar basal HR (DeltaHR after atropine, 11+/-21% versus 62+/-17%; P<0.001), consistent with parasympathetic denervation. Incremental infusion of isoproterenol induced a similar increase in HR in patients and control subjects. CONCLUSIONS: Cardiac autonomic denervation in familial amyloid polyneuropathy results in an upregulation of myocardial muscarinic receptors but without change in cardiac beta-receptor responsiveness to catecholamines. (+info)Results of liver transplantation for familial amyloid polyneuropathy type I in Brazil. (4/93)
Familial amyloid polyneuropathy type I (FAP-I) is an inherited amyloidosis secondary to systemic deposition of amyloid fibrils containing mutant transthyretin (TTR) variants. The disease has a progressive clinical course and is usually fatal 10 years after its onset. TTR is mainly produced in hepatocytes, and liver transplantation (LT) has been proposed as an effective treatment for FAP-I. The aim of this study is to evaluate the results of LT for FAP-I in Brazil and analyze prognostic factors associated with survival after surgery. Twenty-four patients (median age, 36 years; range, 25 to 52 years) who underwent LT with the diagnosis of FAP-I were evaluated. Surgery was uneventful in all but six patients who died of complications of primary liver nonfunction (n = 1), cardiogenic shock (n = 1), sepsis (n = 3), and hepatic artery thrombosis (n = 3). Overall 1- and 5-year survival rates were 70% and 58%, respectively. Most patients had stabilization or improvement of symptoms after a median follow-up of 36 months (range, 14 to 82 months). Survivors had a shorter disease duration before LT (median, 6 years; range, 2 to 17 years v 9 years; range, 7 to 12 years; P =.02), greater albumin levels (median, 4 g/dL; range, 3 to 4.7 g/dL v 3.6 g/dL; range, 2.6 to 4.1 g/dL; P =.03), and greater modified body mass index scores (median, 735; range, 502 to 1,432 v 659; range, 411 to 803; P =.04) compared with nonsurvivors. However, only disease duration and albumin levels were independently associated with survival in multivariate analysis. In conclusion, LT is an effective therapy for FAP-I. Mortality after surgery is associated with poor nutritional status and long-standing disease before LT. Thus, LT should be performed as early as possible after the onset of FAP-I symptoms to avoid major disability and improve survival. (+info)Long-term follow-up of survival of liver transplant recipients with familial amyloid polyneuropathy (Portuguese type). (5/93)
Portuguese type familial amyloid polyneuropathy is a dominantly inherited neuropathic amyloidosis caused by a mutant transthyretin (TTR). Because TTR is produced mainly by the liver, liver transplantation (LT) abolishes production of the amyloidogenic variant TTR. To date, the procedure appears to halt the progress of the disease. However, long-term outcome is unknown. The aim of the present study is to evaluate the survival of our initial group of unselected liver transplant recipients with FAP. Seventy patients, 51 transplant recipients and a control group of 19 nontransplantation patients, with disease onset before the age of 55 years were included on the study. Transplant recipients were divided into two categories: (1) early series, with patients followed up for 5 years or longer, and (2) new series, with patients followed up for 1 to 5 years. Nonparametric statistical methods were used. Binary regression analyses were performed by stepwise logistic regression and Cox proportional hazard regression. Survival analysis was performed using Kaplan-Meier analysis, the Cox-Mantel test. Survival analyses and Cox proportional hazard regression analysis were performed from disease onset, not from LT. Significantly decreased survival was noted for transplant recipients with a modified body mass index (mBMI) less than 600 compared with the control group (P < .05). A significant difference in survival also was observed between transplant recipients with an mBMI greater than 600 at the time of LT compared with those with an mBMI less than 600 (P < .02). mBMI and age at LT had a significant impact on survival; whereas late deaths were related to age at LT, early deaths were related to mBMI. The cumulative 10-year survival rate after disease onset was 94% in the new series, with one early death (< 6 months) after LT, compared with a 78% survival rate and eight early deaths in the early series (P = .1). (+info)Effect of the intestinal flora on amyloid deposition in a transgenic mouse model of familial amyloidotic polyneuropathy. (6/93)
Familial amyloidotic polyneuropathy (FAP) is a hereditary disease characterized by the systemic accumulation of amyloid fibrils. A mutant transthyretin (TTR) gene is mainly responsible for the disease. However, the variable age of onset and low penetrance might be due to environmental factors, one of which is the intestinal flora. Three types of intestinal flora were introduced into a transgenic (Tg) mouse FAP model, 6.0-hMet30. The CV1 and CV2 group transgenic mice were transferred with the intestinal flora from two different mouse facilities housed under conventional conditions, and the SPF group transgenic mice were kept under specific pathogen free conditions in our facility. All the mice were maintained under controlled temperature, humidity and bacterial conditions. Over a period of 28 months, amyloid was not deposited in the SPF and CV1 groups. In contrast, amyloid was deposited in the esophagus and small intestine of two of the three CV2 mice at 18 months. Many neutrophils infiltrated the lesions. The numbers of tissue neutrophils were higher in the CV2 group than in the SPF and CV1 groups at 18 months. The CV2 flora included fewer gram-positive anaerobic cocci as well as higher proportions of yeasts, staphylococci and enterobacteriaceae compared with the SPF and CV1 flora. These findings suggest that the intestinal flora plays an important role in amyloid deposition. (+info)Evidence for early cytotoxic aggregates in transgenic mice for human transthyretin Leu55Pro. (7/93)
Familial amyloidotic polyneuropathy (FAP) is a lethal autosomal dominant disorder characterized by systemic extracellular deposition of transthyretin (TTR) amyloid fibrils. Several groups have generated transgenic mice carrying human TTR Val30Met, the most common mutation in FAP. To study amyloidogenicity and cytotoxicity of different TTRs, we produced transgenic mice expressing human TTR Leu55Pro, one of the most aggressive FAP-related mutations. TTR deposition and presence of amyloid fibrils was investigated and compared to animals carrying the human TTR Val30Met gene kept under the same conditions. Deposition in a C57BL/6J background (TTR-Leu55Pro mice) and in a TTR-null background [TTR-Leu55Pro X TTR-knockout (KO) mice] was compared. Animals in a C57BL/6J background presented early (1 to 3 months) nonfibrillar TTR deposition but amyloid was absent. In a TTR-null background, presence of amyloid fibrils was detected starting at 4 to 8 months with a particular involvement of the gastrointestinal tract and skin. This data suggested that TTR homotetramers are more prone to fibril formation than TTR murine wild-type/human mutant heterotetramers. The nature of the deposited material was further investigated by immunocytochemistry. Both amorphous aggregates and small TTR fibrils were present in TTR-Leu55Pro X TTR-KO transgenics. We observed that these TTR deposits mimic the toxic effect of TTR deposits in FAP: animals with TTR deposition, present approximately twofold increased levels of nitrotyrosine in sites related to deposition. The TTR-Leu55Pro X TTR-KO mice here described are an important tool for the dual purpose of investigating factors involved in amyloidogenesis and in cytotoxicity of deposited TTR. (+info)Familial ATTR amyloidosis: microalbuminuria as a predictor of symptomatic disease and clinical nephropathy. (8/93)
BACKGROUND: Portuguese type familial amyloid polyneuropathy (FAP) is a neuropathic amyloidosis caused by a mutant transthyretin (TTR). Varying degrees of renal involvement have been reported. Our aim was to assess the value of microalbuminuria (MA) for predicting clinical neurological disease and overt nephropathy in TTR-related amyloidosis. METHODS: All subjects had the TTR Val30Met mutation, and were recruited between 1993 and 1999. We have prospectively evaluated 22 asymptomatic gene carriers (7 male, 15 female; mean age 41.6+/-9.6 years) and 32 patients with neuropathy (14 male, 18 female; 36.8+/-8.8 years, on average, 33.0+/-9.3 years at the onset of neuropathy). We measured urinary albumin excretion every year, if asymptomatic, or every 6 months if already affected. Kidney biopsies were performed in patients with normal urinary albumin excretion, MA, and overt nephropathy, respectively. RESULTS: In asymptomatic carriers, persistent MA was detected in eight (36%) subjects. The presence of MA in asymptomatic gene carriers, compared with those having normal urinary albumin excretion, conferred a 4.8-fold risk of developing neuropathy, usually within the subsequent 3 years. Once neurological signs appeared, nephropathy, manifested as MA, progressed to overt nephropathy in one-half of subjects. In patients with neuropathy, 24 (75%) had MA during follow-up: evolution towards clinical renal disease occurred in 14 (58%) and renal failure occurred in five (21%), always after a course of MA. Proteinuria or renal failure without prior persistent MA were never observed in the present patient cohort. Histopathological evaluation did not reveal glomerular lesions other than amyloid deposits to explain abnormal urinary albumin excretion. The amount of mesangial and vascular-pole amyloid deposits was correlated with the degree of albuminuria. CONCLUSIONS: Microalbuminuria represents the first stage of clinical TTR amyloid nephropathy and is premonitory of neuropathy. Its presence identifies a subgroup of patients who are more prone to develop overt nephropathy. Screening of MA may be important to assess disease onset and to recommend liver transplantation in individuals at risk. (+info)Amyloidosis can affect many different parts of the body, including the nervous system, the heart, the kidneys, the liver, and other organs. In the nervous system, amyloid accumulation can lead to various neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, prion diseases, and others.
Amyloid deposits in the nervous system can cause a range of symptoms including cognitive decline, memory loss, confusion, language impairment, and difficulty with coordination and movement. In addition, amyloid accumulation can lead to inflammation, oxidative stress, and excitotoxicity, which can further exacerbate neurodegeneration.
There are several types of amyloidosis that can affect the nervous system, including:
1. Alzheimer's disease: This is a progressive neurodegenerative disorder that is characterized by the accumulation of beta-amyloid peptides in the brain, leading to cognitive decline and memory loss.
2. Parkinson's disease: This is a neurodegenerative disorder that affects movement, balance, and coordination. It is characterized by the accumulation of alpha-synuclein protein in the brain.
3. Prion diseases: These are a group of rare, progressive neurodegenerative disorders that are caused by misfolded prion proteins. They can affect both the central and peripheral nervous systems.
4. Other forms of amyloidosis: There are several other forms of amyloidosis that can affect the nervous system, including primary lateral sclerosis, progressive supranuclear palsy, and corticobasal degeneration.
Amyloidosis can be diagnosed through a combination of clinical evaluation, imaging studies, and biopsy. Treatment options for amyloidosis vary depending on the underlying cause and severity of the disease. Some common treatments include:
1. Medications: There are several medications that can be used to treat amyloidosis, including cholinesterase inhibitors, dopamine agonists, and memantine.
2. Physical therapy: Physical therapy can help improve mobility, balance, and coordination in people with amyloidosis.
3. Speech therapy: Speech therapy can help improve communication and swallowing difficulties in people with amyloidosis.
4. Occupational therapy: Occupational therapy can help people with amyloidosis adapt to changes in their daily living activities and maintain their independence.
5. Surgery: In some cases, surgery may be necessary to relieve pressure on the brain or spinal cord caused by amyloid accumulation.
Currently, there is no cure for amyloidosis, but early diagnosis and treatment can help manage symptoms and improve quality of life. Research into new treatments and therapies is ongoing, including clinical trials exploring the use of stem cells, gene therapy, and immunotherapy to treat amyloidosis.
Amyloidosis is a condition characterized by extracellular amyloid fibrils that are composed of insoluble, abnormal proteins. These fibrils accumulate in different parts of the body, leading to various symptoms and clinical manifestations depending on the type of protein involved.
There are several types of amyloidosis, including:
* Familial amyloid polyneuropathy (FAP): A rare inherited disorder caused by mutations in the transthyretin (TTR) gene, leading to progressive degeneration of the peripheral nerves.
* Familial amyloid cardiomyopathy: A rare inherited heart condition caused by mutations in the TTR gene, leading to progressive cardiac dysfunction and heart failure.
* Primary lateral sclerosis (PLS): A rare progressive neurodegenerative disorder characterized by weakness of the muscles of the limbs, face, and other parts of the body.
* Callidurin amyloidosis: A rare inherited disorder caused by mutations in the callidurin (CAL) gene, leading to progressive degeneration of the peripheral nerves.
The symptoms of these disorders vary depending on the type and severity of the condition, but may include muscle weakness, atrophy, and wasting; numbness or loss of sensation in the limbs; pain; cramping; and difficulty with walking, balance, and coordination. Diagnosis is typically made through a combination of clinical evaluation, imaging studies (such as MRI), and genetic testing. Treatment options are limited for these disorders and focus on managing symptoms and slowing disease progression.
There are several types of amyloidosis, each with different causes and symptoms. The most common types include:
1. Primary amyloidosis: This type is caused by the production of abnormal proteins in the bone marrow. It mainly affects older adults and can lead to symptoms such as fatigue, weight loss, and numbness or tingling in the hands and feet.
2. Secondary amyloidosis: This type is caused by other conditions, such as rheumatoid arthritis, tuberculosis, or inflammatory bowel disease. It can also be caused by long-term use of certain medications, such as antibiotics or chemotherapy.
3. Familial amyloid polyneuropathy: This type is inherited and affects the nerves in the body, leading to symptoms such as muscle weakness, numbness, and pain.
4. Localized amyloidosis: This type affects a specific area of the body, such as the tongue or the skin.
The symptoms of amyloidosis can vary depending on the organs affected and the severity of the condition. Some common symptoms include:
1. Fatigue
2. Weakness
3. Pain
4. Numbness or tingling in the hands and feet
5. Swelling in the legs, ankles, and feet
6. Difficulty with speech or swallowing
7. Seizures
8. Heart problems
9. Kidney failure
10. Liver failure
The diagnosis of amyloidosis is based on a combination of physical examination, medical history, laboratory tests, and imaging studies. Laboratory tests may include blood tests to measure the levels of certain proteins in the body, as well as biopsies to examine tissue samples under a microscope. Imaging studies, such as X-rays, CT scans, and MRI scans, may be used to evaluate the organs affected by the condition.
There is no cure for amyloidosis, but treatment can help manage the symptoms and slow the progression of the disease. Treatment options may include:
1. Medications to control symptoms such as pain, swelling, and heart problems
2. Chemotherapy to reduce the production of abnormal proteins
3. Autologous stem cell transplantation to replace damaged cells with healthy ones
4. Dialysis to remove excess fluids and waste products from the body
5. Nutritional support to ensure adequate nutrition and hydration
6. Physical therapy to maintain muscle strength and mobility
7. Supportive care to manage pain, improve quality of life, and reduce stress on the family.
In conclusion, amyloidosis is a complex and rare group of diseases that can affect multiple organs and systems in the body. Early diagnosis and treatment are essential to managing the symptoms and slowing the progression of the disease. It is important for patients with suspected amyloidosis to seek medical attention from a specialist, such as a hematologist or nephrologist, for proper evaluation and treatment.
There are several types of diabetic neuropathies, including:
1. Peripheral neuropathy: This is the most common type of diabetic neuropathy and affects the nerves in the hands and feet. It can cause numbness, tingling, and pain in these areas.
2. Autonomic neuropathy: This type of neuropathy affects the nerves that control involuntary functions, such as digestion, bladder function, and blood pressure. It can cause a range of symptoms, including constipation, diarrhea, urinary incontinence, and sexual dysfunction.
3. Proximal neuropathy: This type of neuropathy affects the nerves in the legs and hips. It can cause weakness, pain, and stiffness in these areas.
4. Focal neuropathy: This type of neuropathy affects a single nerve, often causing sudden and severe pain.
The exact cause of diabetic neuropathies is not fully understood, but it is thought to be related to high blood sugar levels over time. Other risk factors include poor blood sugar control, obesity, smoking, and alcohol consumption. There is no cure for diabetic neuropathy, but there are several treatments available to manage the symptoms and prevent further nerve damage. These treatments may include medications, physical therapy, and lifestyle changes such as regular exercise and a healthy diet.
Peripheral Nervous System Diseases can result from a variety of causes, including:
1. Trauma or injury
2. Infections such as Lyme disease or HIV
3. Autoimmune disorders such as Guillain-Barré syndrome
4. Genetic mutations
5. Tumors or cysts
6. Toxins or poisoning
7. Vitamin deficiencies
8. Chronic diseases such as diabetes or alcoholism
Some common Peripheral Nervous System Diseases include:
1. Neuropathy - damage to the nerves that can cause pain, numbness, and weakness in the affected areas.
2. Multiple Sclerosis (MS) - an autoimmune disease that affects the CNS and PNS, causing a range of symptoms including numbness, weakness, and vision problems.
3. Peripheral Neuropathy - damage to the nerves that can cause pain, numbness, and weakness in the affected areas.
4. Guillain-Barré syndrome - an autoimmune disorder that causes muscle weakness and paralysis.
5. Charcot-Marie-Tooth disease - a group of inherited disorders that affect the nerves in the feet and legs, leading to muscle weakness and wasting.
6. Friedreich's ataxia - an inherited disorder that affects the nerves in the spine and limbs, leading to coordination problems and muscle weakness.
7. Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) - an autoimmune disorder that causes inflammation of the nerves, leading to pain, numbness, and weakness in the affected areas.
8. Amyotrophic Lateral Sclerosis (ALS) - a progressive neurological disease that affects the nerve cells responsible for controlling voluntary muscle movement, leading to muscle weakness, atrophy, and paralysis.
9. Spinal Muscular Atrophy - an inherited disorder that affects the nerve cells responsible for controlling voluntary muscle movement, leading to muscle weakness and wasting.
10. Muscular Dystrophy - a group of inherited disorders that affect the nerve cells responsible for controlling voluntary muscle movement, leading to muscle weakness and wasting.
It's important to note that this is not an exhaustive list and there may be other causes of muscle weakness. If you are experiencing persistent or severe muscle weakness, it is important to see a healthcare professional for proper evaluation and diagnosis.
The term "amyloid" refers specifically to the type of protein aggregate that forms these plaques, and is derived from the Greek word for "flour-like." Amyloidosis is the general term used to describe the condition of having amyloid deposits in the body, while Alzheimer's disease is a specific type of amyloidosis that is characterized by the accumulation of beta-amyloid peptides in the brain.
Plaques, amyloid play a central role in the pathogenesis of many neurodegenerative diseases, and understanding their formation and clearance is an area of ongoing research. In addition to their role in Alzheimer's disease, amyloid plaques have been implicated in other conditions such as cerebral amyloid angiopathy, primary lateral sclerosis, and progressive supranuclear palsy.
Plaques, amyloid are composed of a variety of proteins, including beta-amyloid peptides, tau protein, and apolipoprotein E (apoE). The composition and structure of these plaques can vary depending on the underlying disease, and their presence is often associated with inflammation and oxidative stress.
In addition to their role in neurodegeneration, amyloid plaques have been implicated in other diseases such as type 2 diabetes and cardiovascular disease. The accumulation of amyloid fibrils in these tissues can contribute to the development of insulin resistance and atherosclerosis, respectively.
Overall, plaques, amyloid are a complex and multifaceted area of research, with many open questions remaining about their formation, function, and clinical implications. Ongoing studies in this field may provide valuable insights into the pathogenesis of various diseases and ultimately lead to the development of novel therapeutic strategies for these conditions.
In conclusion, plaques, amyloid are a hallmark of several neurodegenerative diseases, including Alzheimer's disease, and have been associated with inflammation, oxidative stress, and neurodegeneration. The composition and structure of these plaques can vary depending on the underlying disease, and their presence is often linked to the progression of the condition. Furthermore, amyloid plaques have been implicated in other diseases such as type 2 diabetes and cardiovascular disease, highlighting their potential clinical significance beyond neurodegeneration. Ongoing research into the mechanisms of amyloid plaque formation and clearance may lead to the development of novel therapeutic strategies for these conditions.
There are several subtypes of HSMN, each with distinct clinical features and inheritance patterns. Some of the most common forms of HSMN include:
1. Charcot-Marie-Tooth disease (CMT): This is the most common form of HSMN, accounting for about 70% of all cases. CMT is caused by mutations in genes that code for proteins involved in the structure and function of peripheral nerves.
2. Hereditary motor and sensory neuropathy (HMSN): This is a group of disorders that affect both the sensory and motor nerves, leading to a range of symptoms including weakness, wasting of muscles, and loss of sensation.
3. Spastic paraparesis (SP): This is a rare form of HSMN that is characterized by weakness and stiffness in the legs, as well as spasticity (increased muscle tone).
4. Hereditary neuropathy with liability to pressure palsies (HNPP): This is a rare form of HSMN that is caused by mutations in the PMP22 gene, which codes for a protein involved in the structure and function of peripheral nerves.
The symptoms of HSMN can vary widely depending on the specific subtype and the severity of the condition. Common symptoms include:
* Weakness and muscle wasting
* Numbness and tingling sensations
* Loss of sensation in the hands and feet
* Muscle cramps and spasms
* Difficulty walking or maintaining balance
There is no cure for HSMN, but treatment options are available to manage symptoms and slow the progression of the disease. These may include:
* Physical therapy to improve muscle strength and mobility
* Occupational therapy to improve daily functioning and independence
* Pain management medications
* Orthotics and assistive devices to aid mobility and balance
* Injections or infusions of immunoglobulins to reduce inflammation and demyelination
It is important for individuals with HSMN to receive regular monitoring and care from a healthcare team, including a neurologist, physical therapist, and other specialists as needed. With appropriate management, many individuals with HSMN are able to lead active and fulfilling lives.
The term "cerebral" refers to the brain, "amyloid" refers to the abnormal protein deposits, and "angiopathy" refers to the damage caused to the blood vessels. CAA is often associated with other conditions such as Alzheimer's disease, Down syndrome, and other forms of dementia.
CAA is a type of small vessel ischemic disease (SVID), which affects the smaller blood vessels in the brain. The exact cause of CAA is not yet fully understood, but it is thought to be related to a combination of genetic and environmental factors. There is currently no cure for CAA, but researchers are working to develop new treatments to slow its progression and manage its symptoms.
Some common symptoms of CAA include:
* Cognitive decline
* Seizures
* Stroke-like episodes
* Memory loss
* Confusion
* Difficulty with coordination and balance
If you suspect you or a loved one may be experiencing symptoms of CAA, it is important to speak with a healthcare professional for proper diagnosis and treatment. A thorough medical history and physical examination, along with imaging tests such as MRI or CT scans, can help confirm the presence of CAA.
While there is no cure for CAA, there are several treatment options available to manage its symptoms and slow its progression. These may include medications to control seizures, improve cognitive function, and reduce inflammation. In some cases, surgery or endovascular procedures may be necessary to repair or remove damaged blood vessels.
It is important to note that CAA is a complex condition, and its management requires a multidisciplinary approach involving neurologists, geriatricians, radiologists, and other healthcare professionals. With proper diagnosis and treatment, however, many individuals with CAA are able to lead active and fulfilling lives.
There are several types of HSANs, each with distinct clinical features and modes of inheritance. Some of the most common forms of HSANs include:
1. Hereditary sensory and autonomic neuropathy type I (HSANI): This is the most common form of HSAN, also known as Familial Dysautonomia (Riley-Day syndrome). It is caused by a mutation in the IVS gene and affects primarily the sensory and autonomic nerves.
2. Hereditary sensory and autonomic neuropathy type II (HSANII): This form of HSAN is caused by mutations in the PMP22 gene and is characterized by progressive weakness and loss of sensation in the limbs, as well as abnormalities in the functioning of the autonomic nervous system.
3. Hereditary sensory and autonomic neuropathy type III (HSANIII): This form of HSAN is caused by mutations in the GRM1 gene and is characterized by progressive loss of sensation and muscle weakness, as well as abnormalities in the functioning of the autonomic nervous system.
4. Hereditary sensory and autonomic neuropathy type IV (HSANIV): This form of HSAN is caused by mutations in the MAG gene and is characterized by progressive loss of sensation and muscle weakness, as well as abnormalities in the functioning of the autonomic nervous system.
The symptoms of HSANs vary depending on the specific type of disorder and can include:
* Progressive loss of sensation in the hands and feet
* Muscle weakness and wasting
* Abnormalities in the functioning of the autonomic nervous system, such as dysfunction of the cardiovascular and gastrointestinal systems
* Abnormalities in the functioning of the sensory nerves, leading to numbness, tingling, or pain
* Abnormalities in the functioning of the motor nerves, leading to weakness and muscle wasting
* Eye problems, such as optic atrophy or difficulty moving the eyes
* Hearing loss or other ear abnormalities
* Cognitive impairment or developmental delays
There is currently no cure for HSANs, but various treatments can help manage the symptoms. These may include:
* Physical therapy to maintain muscle strength and mobility
* Occupational therapy to improve daily functioning and independence
* Pain management medications and other treatments for neuropathic pain
* Assistive devices, such as canes or wheelchairs, to aid with mobility
* Speech therapy to improve communication skills
* Cognitive and behavioral therapies to help manage cognitive impairment and developmental delays
The progression of HSANs can vary depending on the specific type of disorder and the individual affected. Some forms of HSANs may progress slowly over many years, while others may progress more quickly and have a more severe impact on daily functioning. In some cases, HSANs can be associated with other conditions or diseases that can affect the progression of the disorder. For example, some individuals with HSANs may also have other neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) or Alzheimer's disease.
HSANs are rare disorders, and there is currently no cure. However, research into the genetic causes of these disorders is ongoing, and new treatments and therapies are being developed to help manage the symptoms and slow the progression of the disorders. With proper management and support, individuals with HSANs can lead fulfilling lives and achieve their goals.
It is important to note that this condition can be caused by various factors such as diabetes, high blood pressure, and certain medications. It can also be a symptom of other underlying conditions such as carotid artery disease or aneurysm.
Causes:
* Reduced blood flow to the optic nerve due to various factors such as diabetes, high blood pressure, and certain medications
* Other underlying conditions such as carotid artery disease or aneurysm
Symptoms:
* Vision loss or blindness in one or both eyes
* Blurred vision or double vision
* Loss of peripheral vision
* Sensitivity to light
Diagnosis:
* Dilated eye exam
* Imaging tests such as MRI or CT scans
* Blood tests to check for underlying conditions such as diabetes or high blood pressure
Treatment:
* Treatment of underlying conditions such as diabetes or high blood pressure
* Medications to improve blood flow to the optic nerve
* Surgery to repair any blockages in the carotid artery or other underlying conditions.
There are many different causes of polyneuropathy, including:
1. Diabetes: High blood sugar levels over time can damage nerves, leading to numbness, tingling, and pain in the hands and feet.
2. Vitamin deficiencies: Deficiencies in vitamins such as B12 and B6 can cause nerve damage and polyneuropathy.
3. Toxins: Exposure to certain toxins, such as heavy metals or pesticides, can damage nerves and cause polyneuropathy.
4. Infections: Certain infections, such as Lyme disease and HIV, can cause polyneuropathy.
5. Autoimmune disorders: Conditions such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy (CIDP) are autoimmune disorders that can cause polyneuropathy.
6. Trauma: Physical trauma, such as a severe injury or crush injury, can cause polyneuropathy.
7. Cancer: Certain types of cancer, such as lymphoma and leukemia, can cause polyneuropathy.
8. Genetic disorders: Some inherited conditions, such as Charcot-Marie-Tooth disease, can cause polyneuropathy.
The symptoms of polyneuropathy depend on the specific nerves affected and can include:
1. Numbness or tingling in the hands and feet
2. Pain in the hands and feet
3. Weakness in the muscles of the hands and feet
4. Difficulty walking or maintaining balance
5. Loss of reflexes
6. Sensitivity to touch or temperature changes
7. Muscle wasting
8. Decreased dexterity
9. Tremors
10. Autonomic dysfunction (e.g., bowel or bladder problems)
The diagnosis of polyneuropathy is based on a combination of clinical findings, nerve conduction studies, and laboratory tests. Treatment depends on the underlying cause of the condition and may include:
1. Pain management with medications such as pain relievers or anti-seizure drugs
2. Physical therapy to maintain muscle strength and mobility
3. Occupational therapy to improve daily functioning
4. Assistive devices, such as canes or walkers, to aid with mobility
5. Autonomic dysfunction management with medications such as beta blockers or fludrocortisone
6. Plasmapheresis, a procedure that removes harmful antibodies from the blood
7. Immunoglobulin therapy, which can help to reduce inflammation
8. Intravenous immunoglobulin (IVIG) therapy, which can help to reduce inflammation and repair nerve damage
9. Dietary changes, such as increasing protein intake, to support nerve health
10. Avoiding harmful substances, such as alcohol or tobacco, which can worsen the condition.
The symptoms of Alzheimer's disease can vary from person to person and may progress slowly over time. Early symptoms may include memory loss, confusion, and difficulty with problem-solving. As the disease progresses, individuals may experience language difficulties, visual hallucinations, and changes in mood and behavior.
There is currently no cure for Alzheimer's disease, but there are several medications and therapies that can help manage its symptoms and slow its progression. These include cholinesterase inhibitors, memantine, and non-pharmacological interventions such as cognitive training and behavioral therapy.
Alzheimer's disease is a significant public health concern, affecting an estimated 5.8 million Americans in 2020. It is the sixth leading cause of death in the United States, and its prevalence is expected to continue to increase as the population ages.
There is ongoing research into the causes and potential treatments for Alzheimer's disease, including studies into the role of inflammation, oxidative stress, and the immune system. Other areas of research include the development of biomarkers for early detection and the use of advanced imaging techniques to monitor progression of the disease.
Overall, Alzheimer's disease is a complex and multifactorial disorder that poses significant challenges for individuals, families, and healthcare systems. However, with ongoing research and advances in medical technology, there is hope for improving diagnosis and treatment options in the future.
Familial amyloid neuropathy
Familial amyloid polyneuropathy
Electrochemical skin conductance
Neuropathy (disambiguation)
List of MeSH codes (C10)
List of MeSH codes (C18)
List of MeSH codes (C16)
Familial Amyloidosis, Finnish Type
Transthyretin
Lattice corneal dystrophy
Mary Reilly (academic)
List of OMIM disorder codes
Cardiac amyloidosis
Carpal tunnel syndrome
List of diseases (C)
Ardalan-Shoja-Kiuru syndrome
Amyloidosis
MFN2
Sarcoidosis
List of MeSH codes (C14)
SOD1
List of skin conditions
Epigenetics of neurodegenerative diseases
Transthyretin amyloidosis: MedlinePlus Genetics
Autonomic Nervous System Anatomy: Overview, Gross Anatomy, Cardiac and Vascular Regulation
DeCS
Amyloid neuropathies. Medical search
Inotersena para o tratamento da polineuropatia amiloidótica familiar relacionada à transtirretina em pacientes adultos em...
HuGE Navigator|Genopedia|PHGKB
DeCS 2016 - June 12, 2016 version
Detekce hereditárních amyloidóz | preLekára.sk
KAKEN - Researchers | TAKEICHI Takayuki (00380999)
BIGG
Stock Market | thepilotnews.com | Flex BLOX CMS
Depression as the middle-and long-term impact for pre-symptomatic testing of late-onset neurodegenerative disorders
Amyloidosis | GOTO 95
DREAMing about arthritic pain | Annals of the Rheumatic Diseases
Baby’s Pregnancy Calendar
Search All Tech Briefings - NIHR
2020 Guidelines of the Polish Society of Laboratory Diagnostics (PSLD) and the Polish Lipid Association (PoLA) on laboratory...
The endoplasmic reticulum (ER) is an integral organelle regulating intracellular Ca2+ - Gene editing with CRISPR
CLASSIFICATION OF DISEASES AND INJURIES
Hello world! | ファントムグループ
Biopsy | Scholars@Duke
About Us
Endocrinology and Metabolism
RegenerativeMedicine.net - Article Archives
Cav2 Mouse Gene Details | caveolin 2 | International Mouse Phenotyping Consortium
Comprehensive Medical Encyclopedia | Education for Healthcare Professionals
Polyneuropathy15
- In addition to the acquired causes, inherited disorders like hereditary sensory-autonomic neuropathy (HSAN), familial amyloid polyneuropathy (FAP), Tangier disease, and Fabry disease also exist. (medscape.com)
- Familial amyloid polyneuropathy (FAP) or transthyretin (TTR) amyloid polyneuropathy , is a rare genetic condition that shares symptoms with other neuropathic disorders. (fcneurology.net)
- Familial amyloid polyneuropathy is a progressive disease caused by the abnormal deposits of proteins or amyloids around the peripheral nervous system. (fcneurology.net)
- Organ damage can occur over time as a result of Familial amyloid polyneuropathy. (fcneurology.net)
- Symptoms of familial amyloid polyneuropathy include numbness or a burning sensation in the hands and feet (peripheral neuropathy) and autonomic neuropathy nerves that control blood pressure, temperature control, and digestion, are damaged. (fcneurology.net)
- Transthyretin familial amyloid polyneuropathy (TTR-FAP) is caused by mutations in the transthyretin gene and affects an estimated 10,000 people worldwide. (fcneurology.net)
- If you are looking for a Familiar Amyloid Polyneuropathy specialist, call (305) 936-9393 to schedule a n appointment with Dr. Jeffrey Gelblum. (fcneurology.net)
- Familial amyloid polyneuropathy (also known as transthyretin amyloidosis, TTR, and FAP) is an inherited disease that causes progressive sensorimotor and autonomic nerve disorder. (fcneurology.net)
- Patients with familial amyloid polyneuropathy may also experience unexplained carpal tunnel syndrome and gastrointestinal disturbances. (fcneurology.net)
- Transthyretin is known to be associated with the amyloid diseases familial amyloid polyneuropathy and familial amyloid cardiomyopathy. (fcneurology.net)
- The symptoms of Familial Amyloid Polyneuropathy include peripheral neuropathy and autonomic neuropathy. (fcneurology.net)
- Familial Amyloid Polyneuropathy is caused by mutations in the TTR gene. (fcneurology.net)
- Neurologist, Dr. Jeffrey Gelblum , has been in practice for over 25 years and possesses a keen interest in the diagnosis and treatment of Familial Amyloid Polyneuropathy. (fcneurology.net)
- Vutrisiran was previously granted Orphan Drug Designation in the European Union (EU) and U.S. for the treatment of ATTR amyloidosis and in Japan for transthyretin type familial amyloidosis with polyneuropathy. (thepilotnews.com)
- This cross-sectional study investigated depression as the middle- (4 years) and long-term (7 and 10 years) psychological impact of pre-symptomatic testing (PST) for 3 autosomal dominant late-onset diseases: Huntington's disease (HD), Machado-Joseph disease (MJD) and familial amyloidotic polyneuropathy (FAP) TTR V30M. (bvsalud.org)
Amyloidosis11
- Transthyretin amyloidosis is a slowly progressive condition characterized by the buildup of abnormal deposits of a protein called amyloid (amyloidosis) in the body's organs and tissues. (medlineplus.gov)
- The neuropathic form of transthyretin amyloidosis primarily affects the peripheral and autonomic nervous systems, resulting in peripheral neuropathy and difficulty controlling bodily functions. (medlineplus.gov)
- Occasionally, people with the cardiac form of transthyretin amyloidosis have mild peripheral neuropathy. (medlineplus.gov)
- AA amyloidóza (amyloid A amyloidosis). (prelekara.sk)
- Amyloidosis is a group of diseases in which abnormal protein s, known as amyloid fibrils , build up in tissue. (goto95.com)
- In wild-type ATTR amyloidosis, non-cardiac symptoms include: bilateral carpal tunnel syndrome , lumbar spinal stenosis , biceps tendon rupture, small fiber neuropathy , and autonomic dysfunction . (goto95.com)
- The four most common types of systemic amyloidosis are light chain (AL) , inflammation ( AA ), dialysis-related (AB 2 M), and hereditary and old age ( ATTR and Wild-type transthyretin amyloid ). (goto95.com)
- The presentation of amyloidosis is broad and depends on the site of amyloid accumulation. (goto95.com)
- As cardiac amyloidosis progresses, the amyloid deposition can affect the heart's ability to pump and fill blood as well as its ability to maintain normal rhythm, which leads to worsening heart function and decline in people's quality of life. (goto95.com)
- People with amyloidosis do not get central nervous system involvement but can develop sensory and autonomic neuropathies. (goto95.com)
- For example, peripheral neuropathy can cause erectile dysfunction, incontinence and constipation, pupillary dysfunction, and sensory loss depending on the distribution of amyloidosis along different peripheral nerves. (goto95.com)
Hereditary1
- HMSN V refers to a condition marked by a hereditary motor and sensory neuropathy associated with spastic paraplegia (see SPASTIC PARAPLEGIA, HEREDITARY). (lookformedical.com)
FIBRILS4
- It is the circulating precusor of amyloid A protein, which is found deposited in AA type AMYLOID FIBRILS. (lookformedical.com)
- Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues. (lookformedical.com)
- Islet amyloid polypeptide can fold into AMYLOID FIBRILS that have been found as a major constituent of pancreatic AMYLOID DEPOSITS. (lookformedical.com)
- Transthyretin gathers forming amyloid fibrils that build up in nerve and heart tissues to cause symptoms of the disease. (fcneurology.net)
Mutations in the transthyretin1
- It is caused by congenital pathological mutation in genes coding for precursor of amyloid fibers, in most case mutations in the transthyretin (TTR) gene. (prelekara.sk)
Deposition4
- Inherited disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. (bvsalud.org)
- A group of sporadic, familial and/or inherited, degenerative, and infectious disease processes, linked by the common theme of abnormal protein folding and deposition of AMYLOID. (lookformedical.com)
- Amyloid deposition in the kidney often involve the glomerular capillaries and mesangial regions , affecting the organ's ability to filter and excrete waste and retain plasma protein . (goto95.com)
- Amyloid deposition in the heart can cause both diastolic and systolic heart failure . (goto95.com)
Sensory3
- Painful burning feet is caused by a sensory neuropathy with small fiber involvement in more than 90% of cases. (medscape.com)
- Elderly patients who lack sural sensory responses can still be diagnosed with small fiber neuropathy. (medscape.com)
- Sensory neuropathy develops in a symmetrical pattern and progresses in a distal to proximal manner. (goto95.com)
Disorders1
- Accumulation of amyloid proteins in the gastrointestinal system may be caused by a wide range of amyloid disorders and have different presentations depending on the degree of organ involvement. (goto95.com)
Diseases1
- Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. (lookformedical.com)
Proteins2
- The amyloid structure has also been found in a number of functional proteins that are unrelated to disease. (lookformedical.com)
- We previously reported that overexpression of Herp promotes neuronal success, whereas knockdown of Herp proteins by small disturbance RNA enhances vulnerability to ER tension- and amyloid -peptide-induced apoptosis (16). (crispr-reagents.com)
PRECURSOR1
- It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. (lookformedical.com)
Deposits2
- Protein deposits in these nerves result in a loss of sensation in the extremities (peripheral neuropathy). (medlineplus.gov)
- As the amyloid deposits enlarge they displace normal tissue structures, causing disruption of function. (lookformedical.com)
Fibers1
- Electromyography (EMG) plays a key role in the evaluation of most peripheral neuropathies and helps in assessing only large myelinated fibers. (medscape.com)
Hypertrophic1
- HMSN III refers to hypertrophic neuropathy of infancy. (lookformedical.com)
Alzheimer's1
- An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). (lookformedical.com)
Autosomal dominant1
- Some familial subtypes demonstrate an autosomal dominant pattern of inheritance. (lookformedical.com)
Nerve2
- Nerve damage that causes pain, tingling, numbness, or weakness in the extremities is known as peripheral neuropathy, and it can cause impairment in sensation or both sensation and strength. (yalemedicine.org)
- The neurologic evaluation of FAP includes obtaining a family history, a physical exam to identify carpal tunnel syndrome or other clinical signs of neuropathy, a nerve test, and confirmatory genetic testing to search for mutations in the TTR gene. (fcneurology.net)
Plaque1
- The window of shilly-shally between amyloid plaque casting and incident of NFTs is about 14 months, with the cognitive shortfall following the neuronal toxicity from the NFTs. (phantom-fc.com)
Genes1
- It's been proven that many genes that are mutated in familial PD encode for protein that have features associated with UPP and mitochondria (1C3). (crispr-reagents.com)
Impairment2
- In the HELIOS-A study, AMVUTTRA met the primary and all secondary endpoints of the study at both 9 months and 18 months , demonstrating reversal in neuropathy impairment and an encouraging safety and tolerability profile. (thepilotnews.com)
- AMVUTTRA demonstrated improvement in the mean change from baseline in modified Neuropathy Impairment Score + 7 (mNIS+7) at 18 months (the primary endpoint for the EU), as compared to external placebo data from the landmark APOLLO Phase 3 study of patisiran. (thepilotnews.com)
Peripheral nerves1
- When a person has peripheral neuropathy, one or more peripheral nerves are unable to communicate properly with the brain, skin, and muscles. (yalemedicine.org)
Develops1
- Peripheral neuropathy is a condition that develops when nerves in the peripheral nervous system, which is located outside of the brain and spinal cord, become damaged and don't function properly. (yalemedicine.org)
Diabetes4
- Peripheral neuropathy is very common among people with diabetes. (yalemedicine.org)
- The longer a person has diabetes, particularly if it isn't well-controlled, the more likely it is that he or she will develop peripheral neuropathy. (yalemedicine.org)
- There is no cure for peripheral neuropathy, but controlling underlying conditions (like diabetes) and managing symptoms may prevent the problem from worsening. (yalemedicine.org)
- Diabetes is the most common cause of peripheral neuropathy. (yalemedicine.org)
Nerves2
- Sometimes, peripheral neuropathy may occur if nerves are compressed. (yalemedicine.org)
- Autonomic neuropathy occurs when there is damage to the nerves that manage your blood pressure, heart rate, sweating, bladder emptying, and digestion. (fcneurology.net)
Sensation1
- Peripheral neuropathy may begin as an abnormal sensation in the legs and feet (numbness, tingling, or burning). (fcneurology.net)
Involvement1
- Few peripheral neuropathies are associated with pure or predominantly small fiber involvement. (medscape.com)
Light chain1
- Mezi získané amyloidózy řadíme AL (amyloid light chain) amyloidózu, která se vyskytuje samostatně nebo u nemocných s monoklonálními gamapatiemie, především trpících mnohočetným myelomem, lymfomy nebo Waldenströmovou makroglobulinémií. (prelekara.sk)
Small1
- Thus, pure small fiber neuropathies may be associated with normal findings on routine electrophysiologic studies. (medscape.com)
Affect2
- Most peripheral neuropathies affect all fiber sizes. (medscape.com)
- Peripheral neuropathy typically affects the feet and lower legs, but it may also affect the hands and arms. (yalemedicine.org)
Primary1
- Familial, primary (nonfamilial), and secondary forms have been described. (lookformedical.com)
Study1
- Results of the HELIOS-A study were published in Amyloid in July, 2022. (thepilotnews.com)
Present1
- Autonomic neuropathy can present as orthostatic hypotension but may manifest more gradually with nonspecific gastrointestinal symptoms like constipation, nausea, or early satiety. (goto95.com)