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The main symptoms of ADA deficiency are pneumonia, chronic diarrhea, and widespread skin rashes. Affected children also grow much more slowly than healthy children and some have developmental delay. Most individuals with ADA deficiency are diagnosed with SCID in the first 6 months of life.
Adenosine deaminase deficiency (also called ADA deficiency or ADA-SCID) is an autosomal recessive metabolic disorder that causes immunodeficiency. It occurs in fewer than one in 100,000 live births worldwide.
It accounts for about 15% of all cases of severe combined immunodeficiency (SCID).
ADA deficiency may be present in infancy, childhood, adolescence, or adulthood. Age of onset and severity is related to some 29 known genotypes associated with the disorder.
Severe combined immunodeficiency, SCID, also known as alymphocytosis, Glanzmann–Riniker syndrome, severe mixed immunodeficiency syndrome, and thymic alymphoplasia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in heterogeneous clinical presentations. SCID involves defective antibody response due to either direct involvement with B lymphocytes or through improper B lymphocyte activation due to non-functional T-helper cells. Consequently, both "arms" (B cells and T cells) of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is the most severe form of primary immunodeficiencies, and there are now at least nine different known genes in which mutations lead to a form of SCID. It is also known as the bubble boy disease and bubble baby disease because its victims are extremely vulnerable to infectious diseases and some of them, such as David Vetter, have become famous for living in a sterile environment. SCID is the result of an immune system so highly compromised that it is considered almost absent.
SCID patients are usually affected by severe bacterial, viral, or fungal infections early in life and often present with interstitial lung disease, chronic diarrhoea, and failure to thrive. Ear infections, recurrent "Pneumocystis jirovecii" (previously carinii) pneumonia, and profuse oral candidiasis commonly occur. These babies, if untreated, usually die within one year due to severe, recurrent infections unless they have undergone successful hematopoietic stem cell transplantation.
About half of US states are performing screening for SCID in newborns using real-time quantitative PCR to measure the concentration of T-cell receptor excision circles. Wisconsin and Massachusetts (as of February 1, 2009) screen newborns for SCID. Michigan began screening for SCID in October 2011. Some SCID can be detected by sequencing fetal DNA if a known history of the disease exists. Otherwise, SCID is not diagnosed until about six months of age, usually indicated by recurrent infections. The delay in detection is because newborns carry their mother's antibodies for the first few weeks of life and SCID babies look normal.
The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infections or developmental delay as a result of infection. Particular organ problems (e.g. diseases involving the skin, heart, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer, such as lymphoma). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.
These are a few specialized autoimmune disorders resulting from environmental rather than genetic causes, which mimic the genotypic disorders.
Impaired fasting glucose is often without any signs or symptoms, other than higher than normal glucose levels being detected in an individual's fasting blood sample. There may be signs and symptoms associated with elevated blood glucose, though these are likely to be minor, with significant symptoms suggestive of complete progression to type 2 diabetes. Such symptoms include:
- Increased thirst
- Increased urination, especially waking up in the night to urinate
- Tiredness and fatigue
- Blurred vision
- Slow healing of wounds
- Altered sensation, such as numbness or tingling, particularly of the hands and feet
- Recurrent, and difficult to clear infections, particularly of the urinary tract
As impaired fasting glucose is considered a precursor condition for type 2 diabetes, it shares the same environmental and genetic risk factors.
Prediabetes typically has no distinct signs or symptoms except the sole sign of high blood sugar. Patients should monitor for signs and symptoms of type 2 diabetes mellitus. These include the following:
- Constant hunger
- Unexplained weight loss
- Weight gain
- Flu-like symptoms, including weakness and fatigue
- Blurred vision
- Slow healing of cuts or bruises
- Tingling or loss of feeling in hands or feet
- Recurring gum or skin infections
- Recurring vaginal or bladder infections
- A high BMI (Body Mass Index) result
Impaired glucose tolerance (IGT) is a pre-diabetic state of dysglycemia, that is associated with insulin resistance and increased risk of cardiovascular pathology. IGT may precede type 2 diabetes mellitus by many years. IGT is also a risk factor for mortality.
The classic symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss. Other symptoms that are commonly present at diagnosis include a history of blurred vision, itchiness, peripheral neuropathy, recurrent vaginal infections, and fatigue. Many people, however, have no symptoms during the first few years and are diagnosed on routine testing. A small number of people with type 2 diabetes mellitus can develop a hyperosmolar hyperglycemic state (a condition of very high blood sugar associated with a decreased level of consciousness and low blood pressure).
Type 2 diabetes is typically a chronic disease associated with a ten-year-shorter life expectancy. This is partly due to a number of complications with which it is associated, including: two to four times the risk of cardiovascular disease, including ischemic heart disease and stroke; a 20-fold increase in lower limb amputations, and increased rates of hospitalizations. In the developed world, and increasingly elsewhere, type 2 diabetes is the largest cause of nontraumatic blindness and kidney failure. It has also been associated with an increased risk of cognitive dysfunction and dementia through disease processes such as Alzheimer's disease and vascular dementia. Other complications include acanthosis nigricans, sexual dysfunction, and frequent infections.
Hearing loss is sensory, but may have accompanying symptoms:
- pain or pressure in the ears
- a blocked feeling
There may also be accompanying secondary symptoms:
- hyperacusis, heightened sensitivity to certain volumes and frequencies of sound, sometimes resulting from "recruitment"
- tinnitus, ringing, buzzing, hissing or other sounds in the ear when no external sound is present
- vertigo and disequilibrium
- tympanophonia, abnormal hearing of one's own voice and respiratory sounds, usually as a result of a patulous eustachian tube or dehiscent superior semicircular canals
- disturbances of facial movement (indicating possible tumour or stroke)
Human hearing extends in frequency from 20-20,000 Hz, and in amplitude from 0 dB to 130 dB or more. 0 dB does not represent absence of sound, but rather the softest sound an average unimpaired human ear can hear; some people can hear down to -5 or even -10 dB. 130 dB represents the threshold of pain. But the ear doesn't hear all frequencies equally well; hearing sensitivity peaks around 3000 Hz. There are many qualities of human hearing besides frequency range and amplitude that can't easily be measured quantitatively. But for many practical purposes, normative hearing is defined by a frequency versus amplitude graph, or audiogram, charting sensitivity thresholds of hearing at defined frequencies. Because of the cumulative impact of age and exposure to noise and other acoustic insults, 'typical' hearing may not be normative.
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have a negative effect on health. People are generally considered obese when their body mass index (BMI), a measurement obtained by dividing a person's weight by the square of the person's height, is over , with the range defined as overweight. Some East Asian countries use lower values. Obesity increases the likelihood of various diseases and conditions, particularly cardiovascular diseases, type 2 diabetes, obstructive sleep apnea, certain types of cancer, osteoarthritis and depression.
Obesity is most commonly caused by a combination of excessive food intake, lack of physical activity, and genetic susceptibility. A few cases are caused primarily by genes, endocrine disorders, medications, or mental disorder. The view that obese people eat little yet gain weight due to a slow metabolism is not generally supported. On average, obese people have a greater energy expenditure than their normal counterparts due to the energy required to maintain an increased body mass.
Obesity is mostly preventable through a combination of social changes and personal choices. Changes to diet and exercising are the main treatments. Diet quality can be improved by reducing the consumption of energy-dense foods, such as those high in fat and sugars, and by increasing the intake of dietary fiber. Medications may be used, along with a suitable diet, to reduce appetite or decrease fat absorption. If diet, exercise, and medication are not effective, a gastric balloon or surgery may be performed to reduce stomach volume or length of the intestines, leading to feeling full earlier or a reduced ability to absorb nutrients from food.
Obesity is a leading preventable cause of death worldwide, with increasing rates in adults and children. In 2015, 600 million adults (12%) and 100 million children were obese. Obesity is more common in women than men. Authorities view it as one of the most serious public health problems of the 21st century. Obesity is stigmatized in much of the modern world (particularly in the Western world), though it was seen as a symbol of wealth and fertility at other times in history and still is in some parts of the world. In 2013, the American Medical Association classified obesity as a disease.
Elective mutism was defined as a refusal to speak in almost all social situations (despite normal ability to do so), while selective mutism is considered to be a "failure" to speak in specific situations and is strongly associated with social anxiety disorder. In contrast to selective mutism, someone who is electively mute may not speak in any situation, as is usually shown in books and movies. Elective mutism is often attributed to defiance or the effect of trauma.
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health. It is defined by body mass index (BMI) and further evaluated in terms of fat distribution via the waist–hip ratio and total cardiovascular risk factors. BMI is closely related to both percentage body fat and total body fat.
In children, a healthy weight varies with age and sex. Obesity in children and adolescents is defined not as an absolute number but in relation to a historical normal group, such that obesity is a BMI greater than the 95th percentile. The reference data on which these percentiles were based date from 1963 to 1994, and thus have not been affected by the recent increases in weight. BMI is defined as the subject's weight divided by the square of their height and is calculated as follows.
BMI is usually expressed in kilograms per square metre, resulting when weight is measured in kilograms and height in metres. To convert from pounds per square inch multiply by .
The most commonly used definitions, established by the World Health Organization (WHO) in 1997 and published in 2000, provide the values listed in the table.
Some modifications to the WHO definitions have been made by particular organizations. The surgical literature breaks down class II and III obesity into further categories whose exact values are still disputed.
- Any BMI ≥ 35 or 40 kg/m is "severe obesity".
- A BMI of ≥ 35 kg/m and experiencing obesity-related health conditions or ≥40–44.9 kg/m is "morbid obesity".
- A BMI of ≥ 45 or 50 kg/m is "super obesity".
As Asian populations develop negative health consequences at a lower BMI than Caucasians, some nations have redefined obesity; Japan have defined obesity as any BMI greater than 25 kg/m while China uses a BMI of greater than 28 kg/m.
Abrasion is a pathological, non-carious tooth loss that most commonly affects the premolars and canines. Abrasion frequently presents at the cemento-enamel junction and can be caused by many contributing factors, all with the ability to affect the tooth surface in varying degrees.
Sources of abrasion may arise from oral hygiene habits such as toothbrushes, toothpicks, floss, and dental appliance or may arise from other habits such as nail biting, chewing tobacco or another object. Abrasion can also occur from the type of dentifrice being utilized as some have more abrasive qualities such as whitening toothpastes.
The appearance may vary depending on the aetiology of abrasion, however most commonly presents in a V-shaped caused by excessive lateral pressure whilst tooth-brushing. The surface is shiny rather than carious, and sometimes the ridge is deep enough to see the pulp chamber within the tooth itself.
In order for successful treatment of abrasion to occur, the aetiology first needs to be identified and ceased, e.g. overzealous brushing. Once this has occurred subsequent treatment may involve the changes in oral hygiene or toothpaste, application of fluoride to reduce sensitivity or the placement of a restoration to aid in reducing the progression of further tooth loss.
The aetiology of dental abrasion can be due to a single stimuli or, as in most cases, multi-factorial. The most common cause of dental abrasion, is the combination of mechanical and chemical wear.
Tooth brushing is the most common cause of dental abrasion, which is found to develop along the gingival margin, due to vigorous brushing in this area. The type of toothbrush, the technique used and the force applied when brushing can influence the occurrence and severity of resulting abrasion. Further, brushing for extended periods of time (exceeding 2-3 min) in some cases, when combined with medium/hard bristled toothbrushes can cause abrasive lesions.
Different toothbrush types are more inclined to cause abrasion, such as those with medium or hard bristles. The bristles combined with forceful brushing techniques applied can roughen the tooth surface and cause abrasion as well as aggravating the gums. Repetitive irritation to the gingival margin can eventually cause recession of the gums. When the gums recede, the root surface is exposed which is more susceptible to abrasion.
Comparatively, electric toothbrushes have less abrasive tendencies.
Types of toothpastes can also damage enamel and dentine due to the abrasive properties. Specific ingredients are used in toothpaste to target removal of the bio-film and extrinsic staining however in some cases can contribute to the pastes being abrasive.
Whitening toothpastes are found to be one of the most abrasive types of toothpastes, according to the RDA Scale, detailed below. In-home and clinical whitening have been proven to increase the likelihood of an individual experiencing dental abrasion. It is believed that dental abrasion due to the whitening process is caused by a combination of both mechanical and chemical irritants, for example, using whitening toothpaste and at home bleaching kits together. However, if an individual is regimented in their after-whitening care then they can avoid loss of dentine minerals and in turn abrasion can be avoided. (that contribute to developing abrasion).
Another factor that can contribute to abrasion is alteration of pH levels in the saliva. This can be sugary/ acidic foods and liquids. The reasoning behind this is that an increase in acidity of saliva can induce demineralization and therefore compromising the tooth structure to abrasive factors such as tooth brushing or normal wear from mastication. When the tooth structure is compromised, this is where the mineral content of the saliva can create shallow depressions in the enamel and thus, when brushed can cause irreparable damage on tooth surface. The dental abrasion process can be further stimulated and accelerated through the effects of dental Acid erosion.
In 1877, a German physician named the disorder "aphasia voluntaria" to describe children who were able to speak normally but often "refused" to.
In 1980, a study by Torey Hayden identified four "subtypes" of Elective Mutism:
- Symbiotic mutism: the most common form, caused by a vocal and dominating mother and absent father (very rarely the other way around) and characterized by the use of mutism as controlling behavior around other adults.
- Speech phobic mutism: the least common, in which the child showed distinct fear at hearing a recording of his or her voice. This also involved ritualistic behaviors, which may reflect OCD, and was thought to be caused by the child having been told to keep a family secret.
- Reactive mutism: a reaction to trauma and/or abuse, with all children showing symptoms of depression and being notably withdrawn, usually showing no facial expressions. Notably, Hayden admits that some children put in this category had no apparent incident to react to, but they were included because of their symptoms.
- Passive-aggressive mutism: silence is used as a display of hostility, connected to antisocial behavior. Some of the children in her study had reportedly not been mute until age 9-12.
The "Diagnostic and Statistical Manual of Mental Disorders" (DSM), first published in 1952, first included Elective Mutism in its third edition, published in 1980. Elective mutism was described as "a continuous refusal to speak in almost all social situations" despite normal ability to speak. While "excessive shyness" and other anxiety-related traits were listed as associated features, predisposing factors included "maternal overprotection", mental retardation, and trauma. Elective mutism in the third edition revised (DSM III-R) is described similarly as in the third edition except for specifying that the disorder is "not" related to social anxiety disorder.
In 1994, the fourth edition of the DSM reflected the name change to selective mutism and redefined the disorder.