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1 Phenylketonuria
(PKU) is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional.[1]:541 This enzyme is necessary to metabolize the amino acid phenylalanine (Phe) to the amino acid tyrosine. When PAH activity is reduced, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone), which is detected in the urine.[2] Since its discovery, there have been many advances in its treatment. It can now be successfully managed by the patient under ongoing medical supervision to avoid the more serious side effects. If, however, the condition is left untreated, it can cause problems with brain development, leading to progressive mental retardation, brain damage, and seizures. Early cases of PKU were treated with a low-phenylalanine diet. More recent research has now shown that diet alone may not be enough to prevent the negative effects of elevated phenylalanine levels. Optimal treatment involves maintaining blood Phe levels in a safe range while monitoring diet and cognitive development. There is no cure for PKU, but patients who are diagnosed early and maintain a strict diet can have a normal life span with normal mental development. Phenylketonuria can now be detected during the first few days of life by two reliable mass screening techniques; and its major consequence, severe mental retardation, can be prevented by the early institution of a low phenylalanine diet. Case finding, based on determination of phenylalanine serum levels in newborns before discharge from the hospital, appears to yield an acceptable number of new cases without excessive numbers of false positive or false negative tests at the 4 mg per 100 ml reporting level. Feeding history does not appear to be a major factor in influencing test results. In addition to finding cases of phenylketonuria, newborn blood screening has called attention to another group of infants with hyperphenylalaninemia of other causes. The differential diagnosis in such cases is important because the restrictive diet necessary for patients with phenylketonuria might be harmful to others. Such factors as enzymatic immaturity, heterozygote carriers, maternal enzymatic capacities and other amino-acidemic states must be ruled out by thorough examination. Careful observation, investigation and reporting of experience with these patients will help to eliminate some of the present deficiencies in the knowledge of normal and abnormal amino acid metabolism. 2
Aminoaciduria
Aminoaciduria is the presence of amino acids in the urine. Small amounts of amino acids are also present in normal urine. Increased total urine amino acids may result from metabolic disorders, chronic liver disease or renal disorders. Aminoacidurias can be divided into primary and secondary aminoacidurias.
Abnormal clinical and laboratory findings for urine / Urine test / urination disorder (R80R82, 791)
Red blood cells White blood cells Proteinuria Small molecules Pathogens Hematuria (Microscopic hematuria) Eosinophiluria Albuminuria/Microalbuminuria Myoglobinuria Hemoglobinuria Glycosuria Ketonuria Bilirubinuria Hyperuricosuria/Hypouricosuria Aminoaciduria Bacteriuria
3 Ketonuria
is a medical condition in which ketone bodies are present in the urine. It is seen in conditions in which the body produces excess ketones as an alternative source of energy. It is seen during starvation or more commonly in type I diabetes mellitus. Production of ketone bodies is a normal response to a shortage of glucose, meant to provide an alternate source of fuel from fatty acids.
Pathophysiology
Ketones are metabolic end-products of fatty acid metabolism. In healthy individuals, ketones are formed in the liver and are completely metabolized so that only negligible amounts appear in the urine. However, when carbohydrates are unavailable or unable to be used as an energy source, fat becomes the predominant body fuel instead of carbohydrates and excessive amounts of ketones are formed as a metabolic byproduct. Higher levels of ketones in the urine indicate that the body is using fat as the major source of energy. Ketone bodies that commonly appear in the urine when fats are burned for energy are acetoacetate and betahydroxybutyric acid. Acetone is also produced and is expired by the lungs. [1] Normally, the urine should not contain a noticeable concentration of ketones to give a positive reading. As with tests for glucose, acetone can be tested by a dipstick or by a lab. The results are reported as small, moderate, or large amounts of acetone. A small amount of acetone is a value under 20 mg/dl; a moderate amount is a value of 3040 mg/dl, and a finding of 80 mg/dl or greater is reported as a large amount.
is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium,[1] phosphorus or calcium,[2] potentially leading to fractures and deformity. Rickets is
Rickets
among the most frequent childhood diseases in many developing countries. The predominant cause is a vitamin D deficiency, but lack of adequate calcium in the diet may also lead to rickets (cases of severe diarrhea and vomiting may be the cause of the deficiency). Although it can occur in adults, the majority of cases occur in children suffering from severe malnutrition, usually resulting from famine or starvation during the early stages of childhood. Osteomalacia is the term used to describe a similar condition occurring in adults, generally due to a deficiency of vitamin D.[3] The origin of the word "rickets" is probably from the Old English dialect word 'wrickken', to twist. The Greek derived word "rachitis" (, meaning "inflammation of the spine") was later adopted as the scientific term for rickets, due chiefly to the words' similarity in sound.
Hypocalcemia (low level of calcium in the blood) Tetany (uncontrolled muscle spasms all over the body) Craniotabes (soft skull) Costochondral swelling (aka "rickety rosary" or "rachitic rosary") Harrison's groove Double malleoli sign due to metaphyseal hyperplasia Widening of wrist raises early suspicion, it is due to metaphysial cartilage hyperplasia.
An X-ray or radiograph of an advanced sufferer from rickets tends to present in a classic way: bow legs (outward curve of long bone of the legs) and a deformed chest. Changes in the skull also occur causing a distinctive "square headed" appearance. These deformities persist into adult life if not treated. Long-term consequences include permanent bends or disfiguration of the long bones, and a curved back.
Types
Nutritional Rickets Vitamin D Resistant Rickets Vitamin D Dependent Rickets o Type I o Type II Congenital Rickets
Cause
The primary cause of rickets is a vitamin D deficiency.[4] Vitamin D is required for proper calcium absorption from the gut. Sunlight, especially ultraviolet light, lets human skin cells convert Vitamin D from an inactive to active state. In the absence of vitamin D, dietary calcium is not properly absorbed, resulting in hypocalcaemia, leading to skeletal and dental deformities and neuromuscular symptoms, e.g. hyperexcitability. Foods that contain vitamin D include butter, eggs, fish liver oils, margarine, fortified milk and juice, and oily fishes such as tuna, herring, and salmon. A rare X-linked dominant form exists called Vitamin D resistant rickets. Cases have been reported in Britain in recent years[5] of rickets in children of many social backgrounds caused by inability to make vitamin D because the sun's ultraviolet light was not reaching the skin because of persistent use of strong sunblock, or too much "covering up" in sunlight, or spending too much time indoors. Other cases have been reported among the children of some ethnic groups in which mothers avoid exposure to the sun for religious or cultural reasons, leading to a maternal shortage of vitamin D. [6][7] The British Medical Journal reported in 2010 that doctors in Newcastle on Tyne saw 20 cases of rickets per year.
5 Osteomalacia
Osteomalacia is the softening of the bones caused by defective bone mineralization secondary to inadequate amounts of available phosphorus and calcium, or because of overactive resorption of calcium from the bone as a result of hyperparathyroidism (which causes hypercalcemia, in contrast to other etiologies). [1] Osteomalacia in children is known as rickets, and because of this, use of the term osteomalacia is often restricted to the milder, adult form of the disease. It may show signs as diffuse body pains, muscle weakness, and fragility of the bones. The most common cause of the disease is a deficiency in vitamin D, which is normally obtained from the diet and/or from sunlight exposure. [2]
General characteristics
Osteomalacia is a generalized bone condition in which there is inadequate mineralization of the bone. Many of the effects of the disease overlap with the more common osteoporosis, but the two diseases are significantly different. There are two main causes of osteomalacia: (1) insufficient calcium absorption from the intestine because of lack of dietary calcium or a deficiency of or resistance to the action of vitamin D; and (2) Phosphate deficiency caused by increased renal losses. Osteomalacia is derived from Greek: osteo- which means "bone", and malacia which means "softness". In the past tense of Brazilian narratives, the disease was also known as malacosteon and its Latin-derived equivalent, mollities ossium.
Causes
The causes of adult osteomalacia are varied, but ultimately result in a vitamin D deficiency:
Insufficient nutritional quantities or faulty metabolism of vitamin D or phosphorus Renal tubular acidosis Malnutrition during pregnancy Malabsorption syndrome [3] Hypophosphatemia Chronic renal failure Tumor-induced osteomalacia [4] Long-term anticonvulsant therapy
Coeliac disease
[5]
Clinical features
Osteomalacia in adults starts insidiously as aches and pains in the lumbar (lower back) region and thighs, spreading later to the arms and ribs. The pain is symmetrical, non-radiating and is accompanied by sensitivity in the involved bones. Proximal muscles are weak, and there is difficulty in climbing up stairs and getting up from a squatting position. Due to demineralization bones become less rigid. Physical signs include deformities like triradiate pelvis [6] and lordosis. The patient has a typical "waddling" gait. However, those physical signs may derive from a previous osteomalacial state, since bones do not regain their original shape after they become deformed. Pathologic fractures due to weight bearing may develop. Most of the time, the only alleged symptom is chronic fatigue, while bone aches are not spontaneous but only revealed by pressure or shocks. It differs from renal osteodystrophy, where the latter shows hyperphosphatemia
Biochemical findings
Biochemical features are similar to those of rickets. The major factor is an abnormally low vitamin D concentration in blood serum. Major typical biochemical findings are:
The serum calcium is low Urinary calcium is low Serum phosphate is low except in cases of renal osteodystrophy Serum alkaline phosphatase is high
Phosphate
Alkaline phosphatase
Comments
unaffected unaffected
variable
unaffected
decreased bone mass thick dense bones also known as marble bone
Osteopetrosis
Unaffected unaffected
elevated
unaffected
decreased decreased
variable
elevated
soft bones
elevated
decreased
elevated
elevated
brown tumors
unaffected unaffected
6 Myxedema
(British English: myxoedema) describes a specific form of cutaneous and dermal edema secondary to increased deposition of connective tissue components (like glycosaminoglycans, hyaluronic acid, and other mucopolysaccharides) in subcutaneous tissue as seen in various forms of hypothyroidism and Graves' disease.[1]:535 It is more common in women than in men. [2]
Terminology
The word originates from , taken from ancient Greek to convey 'mucus' or 'slimy substance' and for swelling.
Hyperthyroid: Myxedema typically presents in specific areas (pretibial myxedema and exophthalmos) and is related to high levels of TSH receptor stimulation and/or inflammation mounted against the TSH receptor itself. Myxedema of the lower legs (called pretibial myxedema), can occur in one to four percent of patients with Graves' [3] disease -- a condition that causes hyperthyroidism. Hypothyroid: Myxedema is also used to describe the clinical syndrome secondary to hypothyroidism. Symptoms can include depression, mental slowness, weakness, bradycardia, fatigue, hypothermia, alopecia, and many others (see symptoms of severe hypothyroidism). Used in this way, myxedema can be considered the adult counterpart of [4] cretinism.
Myxedema coma is rare and establishing the diagnosis requires a high index of suspicion. Myxedema coma represents the severest form of hypothyroidism and has an associated mortality rate of 30 percent to 40 percent. It can occur due to long-standing, untreated hypothyroidism, but is often linked to a precipitant, such as acute infection, myocardial infarction, congestive heart failure, cerebral vascular accident, trauma, or drug toxicity. Several medications can cause hypothyroidism, and patients taking them must be carefully monitored. These medications include amiodarone, lithium, and sedatives. No consensus exists on specific
Cause
The increased deposition of glycosaminoglycan is not fully understood, however two mechanisms predominate.
Exophthalmos in particular results from TSH receptor stimulation on fibroblasts behind the eyes which leads to increased glycosaminoglycan deposition. It is thought that many cells responsible for forming connective tissue react to increases in TSH levels. Secondarily, in autoimmune thyroid diseases lymphocytes react to the TSH receptor. Thus, in addition to the inflammation within the thyroid, any cell that expresses the TSH receptor will likely experience lymphocytic infiltrates as well. The inflammation can cause tissue damage and scar tissue formation, explaining the deposition of glycosaminoglycans.
The increased deposition of glycosaminoglycans causes an osmotic edema and fluid collection. Hashimoto's thyroiditis is the most common cause of myxedema in the United States. [6]
7 Hirsutism
on women[3] in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair (androgenic hair) and it is therefore primarily of cosmetic and psychological concern. Hirsutism is a symptom rather than a disease and may be a sign of a more serious medical condition, especially if it develops well after puberty. The amount and location of the hair is measured by a Ferriman-Gallwey score.
Hirsutism is the excessive hairiness
[2]
Hirsutism affects women and sometimes men, since the rising of androgens causes a male pattern of body hair, sometimes excessive, particularly in locations where women normally do not develop terminal hair during puberty (chest, abdomen, back and face). The medical term for excessive hair growth that affect both men and women is hypertrichosis.
Causes
Hirsutism can be caused by either an increased level of androgens, the male hormones, or an oversensitivity of hair follicles to androgens. Male hormones such as testosterone stimulate hair growth, increase size and intensify the growth and pigmentation of hair. Other symptoms associated with a high level of male hormones include acne and deepening of the voice and increased muscle mass. Growing evidence implicates high circulating levels of insulin in women for the development of hirsutism. This theory is speculated to be consistent with the observation that obese (and thus presumably insulin resistant hyperinsulinemic) women are at high risk of becoming hirsute. Further, treatments that lower insulin levels will lead to a reduction in hirsutism. It is speculated that insulin, at high enough concentration, stimulates the ovarian theca cells to produce androgens. There may also be an effect of high levels of insulin to activate the insulin-like growth factor-I (IGF-1) receptor in those same cells. Again, the result is increased androgen production.
Diagnosis
One method of evaluating hirsutism is the Ferriman-Gallwey score which gives a score based on the amount and location of hair growth on a woman.[5] Diagnosis of patients with even mild hirsutism should include assessment of ovulation and ovarian ultrasound (because of the high prevalence of polycystic ovary syndrome, as well as 17-hydroxyprogesterone (because of the possibility of finding nonclassic 21-hydroxylase deficiency.[6] Other blood value that may be evaluated in the workup of hirsutism include:
the androgens testosterone and dehydroepiandrosterone sulfate thyroid-stimulating hormone prolactin
Chronic kidney disease is the slow loss of kidney function over time. The main function of the kidneys is to remove wastes and excess water from the body.
Chronic kidney disease leads to a buildup of fluid and waste products in the body. This condition affects most body systems and functions, including: Blood pressure control Red blood cell production Vitamin D and bone health
Symptoms
The early symptoms of chronic kidney disease are also symptoms of other illnesses. These symptoms may be the only signs of kidney disease until the condition is more advanced. Symptoms may include: Appetite loss General ill feeling and fatigue Headaches Itching (pruritus) and dry skin Nausea Weight loss without trying to lose weight
Other symptoms that may develop, especially when kidney function has gotten worse, include: Abnormally dark or light skin Bone pain Brain and nervous system symptoms: o Drowsiness and confusion o Problems concentrating or thinking o Numbness in the hands, feet, or other areas o Muscle twitching or cramps Breath odor Easy bruising, bleeding, or blood in the stool Excessive thirst
Chronic kidney disease changes the results of several other tests. Every patient needs to have the following checked regularly, as often as every 2 - 3 months when kidney disease gets worse: Albumin Calcium Cholesterol Complete blood count (CBC) Electrolytes Magnesium Phosphorous Potassium Sodium
Causes of chronic kidney disease may be seen on: Abdominal CT scan Abdominal MRI Abdominal ultrasound Kidney biopsy Kidney scan Kidney ultrasound
This disease may also change the results of the following tests:
Diabetes Insipidus,
Diabetes insipidus (DI) causes frequent urination. The large volume of urine is diluted, mostly water. To make up for lost water, you may feel the need to drink large amounts. You are likely to urinate frequently, even at night, which can disrupt sleep or, on occasion, cause bedwetting. Because of the excretion of abnormally large volumes of dilute urine, you may quickly become dehydrated if you do not drink enough water. Children with diabetes insipidus may be irritable or listless and may have fever, vomiting , or diarrhea. In its clinically significant forms, diabetes insipidus is a rare disease.
10 Obesity
Obesity means having too much body fat. It is not the same as being overweight, which means weighing too much. A person may be overweight from extra muscle, bone, or water, as well as from having too much fat. Both terms mean that a person's weight is higher than what is thought to be healthy for his or her height.
Many obese people who lose large amounts of weight and gain it back think it is their fault. They blame themselves for not having the willpower to keep the weight off. Many people regain more weight than they lost. Today, we know that biology is a big reason why some people cannot keep the weight off. Some people who live in the same place and eat the same foods become obese, while others do not. Our bodies have a complex system to help keep our weight at a healthy level. In some people, this system does not work normally. Other factors that affect weight include: The way we eat when we are children can affect the way we eat as adults. The way we eat over many years becomes a habit. It affects what we eat, when we eat, and how much we eat. We are surrounded by things that make it easy to overeat and hard to stay active: o Many people do not have time to plan and make healthy meals. o More people today work desk jobs compared to more active jobs in the past. o People with less free time have less time to exercise.
The term "eating disorder" means a group of medical conditions that have an unhealthy focus on eating, dieting, losing or gaining weight, and body image. A person may be obese, follow an unhealthy diet, and have an eating disorder all at the same time. Sometimes, medical problems or treatments cause weight gain, including: Underactive thyroid gland (hypothyroidism) Medicines such as birth control pills, antidepressants, and antipsychotics
Other things that can cause weight gain are: Quitting smoking. Most people who quit smoking gain 4 - 10 pounds in the first 6 months after quitting. Some people gain as much as 25 - 30 pounds. Stress, anxiety, feeling sad, or not sleeping well
BMI is measured using height and weight. You and your health care provider can use your BMI to estimate how much body fat you have. Your waist measurement is another way to estimate how much body fat you have. Extra weight around your middle or stomach area increases your risk for type 2 diabetes, heart disease, and stroke. People with "appleshaped" bodies (meaning their waist is bigger than their hips) also have an increased risk for these diseases. Skin fold measurements may be taken to check your body fat percentage. Blood tests may be done to look for thyroid or hormone problems that could lead to weight gain.
11 Kidney stones
A kidney stone is a solid mass made up of tiny crystals. One or more stones can be in the kidney or ureter at the same time.
The biggest risk factor for kidney stones is not drinking enough fluids. Kidney stones are more likely to occur if you make less than 1 liter of urine a day. That's slightly more than a quart. .
Symptoms
You may not have symptoms until the stones move down the tubes (ureters) through which urine empties into your bladder. When this happens, the stones can block the flow of urine out of the kidneys. The main symptom is severe pain that starts suddenly and may go away suddenly: Pain may be felt in the belly area or side of the back Pain may move to groin area (groin pain) or testicles (testicle pain)
Other symptoms can include: Abnormal urine color Blood in the urine Chills Fever Nausea Vomiting
Stones or a blockage can be seen on: Abdominal CT scan Abdominal/kidney MRI Abdominal x-rays Intravenous pyelogram (IVP) Kidney ultrasound Retrograde pyelogram
Tumor Antigens
Include markers defined by both monoclonal antibodies and polyclonal antisera, often the so called oncofetal antigens. The oncofetal substances, present in embryo or fetus, diminish to low levels in the adult but reappear in the tumor.
Carcinoembryonic Antigen
Tumor marker, CEA: Carcinoembryonic antigen (CEA) is a protein found in many types of cells but associated with tumors and the developing fetus. CEA is tested in blood. The normal range is <2.5 ng/ml in an adult non-smoker and <5.0 ng/ml in a smoker. The CEA was one of the first oncofetal antigens to be described and exploited clinically. It is a complex glycoprotein of molecular weight 20,000, that is associated with the plasma membrane of tumor cells, from wich it may be released into the blood. Although CEA was first indentified in colon cancer, an abnormal CEA blood level is specific neither for colon cancer nor for malignancy in general. Elevated CEA levels are found in a variety of cancers other than colonic, including pancreatic, gastric, lung, and breast. It is also detected in benign conditions including cirrhosis, inflamatory bowel disease, chronic lung disease, and pancreatitis. The CEA was found to be elevated in up to 19 percent of smokers and in 3 percent of a healthy control population. Thus, the test for CEA cannot substitute for a pathological diagnosis. As a screening test, the CEA is also inadequate. Since cancer prevalence in a healthy population is low, an elevated CEA has an unacceptably low positive predictive value, with excess false positives. Also, since elevated CEA occurs in the advanced stage of incurable cancer but is low in the early, curable disease, the likelihood of a positive result affecting a patient's survival is diminished. The CEA has been sugested as having prognostic value for patients with colon cancer. Preoperative CEA values have been positively correlated with stage and negatively correlated with disease free survival. Although not satisfactory for screening a healthy population, CEA has been used to monitor recurrence. Early data suggested that CEA prededed clinical relapse by several months. Subsequently, several investigators have examined intensive, serial CEA monitoring as an indicator for second look surgery in the hope that relapse could be detected at a time when surgical ressection for cure was still possible. Criteria for reoperation included a significant rise of CEA above a base line level on serial determinations and absence of obvious unresectable disease on staging workup. Determinations of CEA should be done frequently: at a minimum of every 3 months and if possible every 1 month to 2 months. Elevations above baseline should be verified rapidly to exclude laboratory error.
Alpha-Fetoprotein
Alpha-Fetoprotein is a normal fetal serum protein synthesized by the liver, yolk sac, and gastrointestinal tract that shares sequence homology with albumin. It is a major component of fetal plasma, reaching a peak concentration of 3 mg/ml at 12 weeks of gestation. Following birth, it clears rapidily from the circulation, having a half life of 3.5 days, and its concentration in adult serum is less than 20 ng/ml. AFP is of importance in diagnosing hepatocellular carcinoma and may be useful in screening procedures. AFP elevation is more common in areas where hepatocellular carcinoma is endemic, such as Africa and in patients who are HBsAg positive. AFP is a marker for hepatocellular and germ cell (nonseminoma) carcinoma.1 It is a glycoprotein produced in large amounts during fetal life and is homologous to albumin. In healthy adults, less than 10 g/L of AFP is found in the circulation. AFP is elevated in normal pregnancy, benign liver disease (hepatitis, cirrhosis), as well as in cancer. An elevated AFP has been termed by Sell "the single most discriminating laboratory test indicative of malignant disease now available." As such, it could be valuable in screening for hepatocellular carcinoma in high risk populations. AFP is elevated in testicular germ cell tumors containing embryonal or endodermal sinus elements. A defenitive positive marker value is highly sensitive in indicating relapse or response to treatment. The AFP is less frequently elevated in other malignancies such as pancreatic cancers, gastric cancers, colonic cancers, and bronchogenic cancers. This elevation was not necessarily associated with liver metastases. The AFP is rarely elevated in healthy persons, and a rise is seen in only a few disease states. Elevation occurs in certain liver diseases, especially acute viral or drug induced hepatitis and conditions associated with hepatic regeneration. In general, the elevations are under 500 ng/ml and do not denote hepatocellular carcinoma. Is also elevated in ataxiatelangiectasia and in hereditary tyrosinosis. Thus, AFP is a useful marker in hepatocellular carcinoma and germ cell tumors, the only conditions associated with extreme elevations greater than 500 ng/ml. In both tumors it has value in diagnosis and monitoring of therapy. In the former, wich is one of the most common tumors worldwide, AFP may be of use in screening.
CA 125
CA125 is an antigen present on 80 percent of nonmucinous ovarian carcinomas. It is defined by a monoclonal antibody ( OC125 ) that was generated by immunizing laboratory mice with a cell line established from human ovarian carcinoma. It circulates in the serum of patients with ovarian carcinoma and was therefore investigated for possible use as a marker. CA125 is often elevated in patients with ovarian cancer, its level following the patient's clinical course. With surgical resection or chemotherapy, the level correlates with patient response. Thus, it is superior to other markers such as CEA. The CA125 is elevated in other cancers including endometrial, pancreatic, lung, breast, and colon cancer, and in menstruation, pregnancy, endometriosis, and other gynecologic and non gynecologic conditions. Because of the low prevalence of ovarian cancer, the test is not itself useful in screening.
CA19-9
CA19-9 is a monoclonal antibody generated against a colon carcinoma cell line to detect a monosialoganglioside found in patients with gastrointestinal adenocarcinoma. It is found it to be elevated in 21 to 42 percent of cases of gastric cancer, 20 to 40 percent of colon cancer, and 71 to 93 percent of pancreatic cancer, and has been proposed to differentiate benign from malignant pancreatic disease, but this capability remains to be established.