Alpha-mannosidosis is a lysosomal storage disorder, first described by Swedish physician Okerman in 1967. (wikipedia.org)
A defective alpha-mannosidase enzyme, which normally helps to break down complex sugars derived from glycoproteins in the lysosome, causes progressive lysosomal accumulation of mannose-rich oligosaccharides in all tissues, resulting in impaired cellular function and apoptosis (Figure 2). (wikipedia.org)
Alpha-mannosidosis is an autosomal recessive lysosomal storage disease characterized by mental retardation, coarse facial features, skeletal abnormalities, hearing impairment, neurologic motor problems, and immune deficiency. (beds.ac.uk)
Age of onset and clinical manifestations may vary widely among patients with a given lysosomal storage disease, and significant phenotypic heterogeneity between family members carrying identical mutations has been reported. (medscape.com)
In general, transplantation yields the best results when performed early in the course of the disease (ie, in an asymptomatic affected sibling of a child with a lysosomal storage disorder), in centers with experience in performing transplantations to treat inherited metabolic disorders, and in patients healthy enough to tolerate the conditioning and transplantation regimen. (medscape.com)
Angiokeratoma corporis diffusum is the cutaneous hallmark of Fabry disease, an X-linked inherited disorder caused by a deficiency in the lysosomal enzyme alpha-galactosidase A. Decreased or absent enzyme activity causes uncleaved glycosphingolipids to accumulate in various cell types, particularly in the vascular endothelium, smooth muscle cells, and pericytes, causing ischemia and infarction of tissues. (medscape.com)
Angiokeratoma corporis diffusum is not unique to Fabry disease and has also been documented in several other rare lysosomal storage disorders such as fucosidosis, sialidosis, GM1 gangliosidosis, galactosialidosis, beta-mannosidosis, Kanzaki disease, and aspartylglucosaminuria. (medscape.com)
Deficiency or absence of alpha-galactosidase A (α-GAL A) activity as a result of gene mutations in the GLA gene (Xq21.3-q22) leads to lysosomal accumulation of neutral glycosphingolipids, most notably globotriaosylceramide (G3b). (medscape.com)
Deficiency5
In humans it is known to be caused by an autosomal recessive genetic mutation in the gene MAN2B1, located on chromosome 19, affecting the production of the enzyme alpha-D-mannosidase, resulting in its deficiency. (wikipedia.org)
Bloom syndrome (BSyn) is characterized by severe pre- and postnatal growth deficiency, immune abnormalities, sensitivity to sunlight, insulin resistance, and a high risk for many cancers that occur at an early age. (beds.ac.uk)
Symptoms of alpha-1 antitrypsin deficiency include shortness of breath, recurring respiratory infections, or obstructive asthma that does not respond to treatment. (the-medical-dictionary.com)
Severe [[alpha].sub.1]-antitrypsin (AAT) deficiency is a co-dominant autosomal hereditary disorder that manifests clinically as the appearance of pulmonary emphysema at young ages, particularly in smokers. (the-medical-dictionary.com)
Other individuals with alpha-mannosidosis experience milder signs and symptoms that appear later and progress more slowly. (medlineplus.gov)
Type III alpha mannosidosis is the most severe form, and signs and symptoms appear in infancy with rapid progression, severe neurological deterioration, and early death. (ssa.gov)
This is the most common form Type 3: A severe form, leading to early death from progressive central nervous system involvement However, given the variety of mutations that have been documented, and the broad range and severity of symptoms, the disease is considered clinically as a continuum. (wikipedia.org)
Patients may present to doctors, nurses or health visitors at different stages of progression, and with different ad hoc symptoms, making the link to suspect a diagnosis of alpha-mannosidosis difficult. (wikipedia.org)
A high index of suspicion for Fabry disease should be noted, especially when angiokeratomas are seen with other earlier symptoms of the disease (acroparesthesia, hypohidrosis, or heat intolerance). (medscape.com)
While the onset of the disease is very variable, first symptoms might occur at about 12 weeks of age. (labogen.com)
It is currently recommended that patients begin augmentation therapy only after the onset of emphysema symptoms. (the-medical-dictionary.com)
The onset of the most severe form of the disease occurs within the first months of life and involves skeletal abnormalities and intellectual disability, with rapid progression leading to death from primary central nervous system involvement or myopathy. (wikipedia.org)
Age of onset and progression of secondary effects are highly variable but ear folding is a consistent feature. (laboklin.co.uk)
Inheritance1
Fabry disease generally affects men and boys more severely and at an earlier age than women and girls because its inheritance is X-linked (the male sex only carries one X chromosome whereas females have two). (dermnetnz.org)
Phenotypes2
Generally, phenotypes of alpha-mannosidosis patients are not clearly distinguishable, which makes a prediction of the clinical course for an individual patient challenging. (wikipedia.org)
Alpha-mannosidosis encompasses a continuum of clinical findings from mild to severe. (beds.ac.uk)
Infantile3
The earlier system delineated a more severe 'type I,' which shows infantile onset, rapid mental deterioration, hypotonia, splenomegaly, severe dysostosis multiplex, and severe recurrent infections, often resulting in death by age 8 years. (beds.ac.uk)
Infantile-onset represents a more aggressive course, presenting early and leading to a more rapid neurological decline. (radiopaedia.org)
The disease course may be from several years in the late-infantile-onset form to decades in the juvenile- and adult-onset forms. (nih.gov)
Diagnosis3
A confirmed diagnosis is documented by abnormally low or absent levels of alpha-D-mannosidase enzymatic activity in white blood cells. (ssa.gov)
Given the progressive nature of the disease, the earlier a correct diagnosis is achieved the better. (wikipedia.org)
A diagnosis of alpha-mannosidosis is suspected based upon identification of characteristic findings of a multi-symptomatic presentation, a thorough clinical evaluation, a detailed patient history, and results from the diagnostic tests described below: A. Oligosaccharides in urine A preliminary investigation may be performed to measure mannose-rich oligosaccharide concentrations in urine. (wikipedia.org)
Clinical1
Classification Systems Two classification systems have been used to describe the clinical presentation of alpha-mannosidosis. (beds.ac.uk)
Severe form2
A severe form manifested as prenatal loss or early death from progressive central nervous system involvement or infection (type 3). (beds.ac.uk)
Type A, the most severe form, begins in early infancy. (nih.gov)
Ataxia3
Ataxia and features of motor neuron disease are evident early. (arizona.edu)
Friedreich ataxia (FRDA) is characterized by slowly progressive ataxia with onset usually before age 25 years (mean age at onset: 10-15 yrs). (nih.gov)
Type B (juvenile onset) does not generally affect the brain but most children develop ataxia, damage to nerves exiting from the spinal cord (peripheral neuropathy), and pulmonary difficulties that progress with age. (nih.gov)
Complete absence of functionality in this enzyme leads to death during early childhood due to deterioration of the central nervous system. (wikipedia.org)
They present in early childhood with delayed psychomotor development, delayed speech, and hearing loss. (beds.ac.uk)
Individuals with the less severe 'type II' show normal early development with later childhood development of mental retardation, hearing loss, coarse facies, neurologic deterioration, and survival well into adulthood (summary by Desnick et al. (beds.ac.uk)
Early mortality in infancy or childhood is common although some survive into the 2nd and 3rd decades. (arizona.edu)
The majority of individuals with Krabbe disease present in early childhood although adult presentations as late as the 5thdecade are encountered 9 . (radiopaedia.org)
Occurs2
Onset occurs after age 16 years, sometimes not until the fourth or fifth decade. (nih.gov)
Enlargement of the liver and spleen characteristically occurs in the early adolescence. (nih.gov)
Disorder3
Alpha-mannosidosis is a rare inherited disorder that causes problems in many organs and tissues of the body. (medlineplus.gov)
Alpha-mannosidosis is a progressive disorder, and its presence should be suspected in patients with cognitive disabilities, skeletal changes (e.g., swollen joints, curved spine), hearing loss and recurrent infections. (wikipedia.org)
It most commonly presents as a progressive and severe neurodegenerative disorder with onset within the first months or years of life, and may result in early death. (beds.ac.uk)
Adult1
Type C may appear early in life or develop in the teen or even adult years. (nih.gov)
Transplantation1
New and promising therapies for alpha mannosidosis include bone marrow transplantation, enzyme replacement, and gene therapy. (ssa.gov)
Serious medical complications that are more common than in the general population and that also appear at unusually early ages include chronic obstructive pulmonary disease, diabetes mellitus as a result of insulin resistance, and cancer of a wide variety of types and anatomic sites. (beds.ac.uk)
Progressive1
Alpha-mannosidosis is a lifelong multi-systemic progressive disease, with neuromuscular and skeletal deterioration over decades. (wikipedia.org)
Fabry5
The Fabry disease gene is now known as the GLA gene, which stands for alpha-galactosidase. (medscape.com)
Persons with Fabry disease who have type AB or B blood also accumulate blood group B glycosphingolipids (those with alpha-galactosyl-terminated residues) and can have more severe Fabry disease (related to greater body substrate mass) than patients with blood group A. This is because these blood groups have two additional terminal alpha-galactosyl moieties. (medscape.com)
The age of onset of Fabry disease can range from the second to the fifth decade of life or later. (dermnetnz.org)
Fabry disease is caused by a mutation of the alpha-galactosidase A gene ( GLA ) mapped to the long arm of the X chromosome [5]. (dermnetnz.org)
Dermatological manifestations occur in more than 70% of patients with Fabry disease, with a mean age of onset at 17 years [3]. (dermnetnz.org)
Enzyme leads1
Lack of the alpha-galactosidase A enzyme leads to accumulation of Gb3 in various tissues, leading to cell death. (dermnetnz.org)
Residues1
In addition to increasing the inflammatory reaction in the airways, cigarette smoke directly inactivates alpha 1-antitrypsin by oxidizing essential methionine residues to sulfoxide forms, decreasing the enzyme activity by a rate of 2000. (the-medical-dictionary.com)
Years1
Onset is between age 30 months and 16 years. (nih.gov)
Individuals2
Approximately two thirds of individuals with FRDA have cardiomyopathy, up to 30% have diabetes mellitus, and approximately 25% have an "atypical" presentation with later onset or retained tendon reflexes. (nih.gov)
Individuals with alpha-1 may develop emphysema during their thirties or forties, without a history of significant smoking (although smoking greatly increases the risk for emphysema). (the-medical-dictionary.com)
Patients1
In the United States, Canada, and several European countries, lung-affected A1AD patients may receive intravenous infusions of alpha-1 antitrypsin, derived from donated human plasma. (the-medical-dictionary.com)
Carriers1
Females are carriers of the disease and have diminished levels of alpha-galactosidase. (medscape.com)
Defective1
Hepatomegaly and jaundice may also be an early diagnostic feature as bile acid metabolism is defective. (arizona.edu)
Terminal1
The enzyme alpha-galactosidase A catalyses the cleavage (separation) of the terminal galactose from Gb3. (dermnetnz.org)
They have distinctive facies, congenital malformations (neuronal migration defects associated with neonatal-onset seizures, renal cysts, and bony stippling [chondrodysplasia punctata] of the patella[e] and the long bones), and liver disease that can be severe. (nih.gov)
Alpha 1-antitrypsin (AAT) is produced in the liver, and one of its functions is to protect the lungs from the neutrophil elastase enzyme. (the-medical-dictionary.com)
Approximately1
Alpha-mannosidosis is estimated to occur in approximately 1 in 500,000 people worldwide. (medlineplus.gov)