Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substrates ) into others ( products ). In most of the disorders, problems arise due to accumulation of substances which are toxic or interfere with normal function, or due to the effects of reduced ability to synthesize essential compounds. Inborn errors of metabolism are often referred to as congenital metabolic diseases or inherited metabolic disorders . Another term used to describe these disorders is "enzymopathies". This term was created following the study of biodynamic enzymology , a science based on the study of the enzymes and their products. Finally, inborn errors of metabolism were studied for the first time by British physician Archibald Garrod (1857–1936), in 1908. He is known for work that prefigured the "one gene–one enzyme" hypothesis , based on his studies on the nature and inheritance of alkaptonuria. His seminal text, Inborn Errors of Metabolism , was published in 1923.
85-433: Phenylketonuria ( PKU ) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine . Untreated PKU can lead to intellectual disability , seizures , behavioral problems, and mental disorders . It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head , and low birth weight . Phenylketonuria
170-411: A genetic link between the conditions. Diagnosis of eczema is based mostly on the history and physical examination . In uncertain cases, skin biopsy may be taken for a histopathologic diagnosis of dermatitis . Those with eczema may be especially prone to misdiagnosis of food allergies . Patch tests are used in the diagnosis of allergic contact dermatitis. The term eczema refers to
255-465: A heterozygote is advantageous . The PAH gene is located on chromosome 12 in the bands 12q22-q24.2. As of 2000, around 400 disease-causing mutations had been found in the PAH gene. This is an example of allelic genetic heterogeneity . When phenylalanine (Phe) cannot be metabolized by the body, a typical diet that would be healthy for people without PKU causes abnormally high levels of Phe to accumulate in
340-625: A "musty odor" to the baby's sweat and urine (due to phenylacetate , a carboxylic acid produced by the oxidation of phenylacetone). In most cases, a repeat test should be done at approximately two weeks of age to verify the initial test and uncover any phenylketonuria that was initially missed. Untreated children often fail to attain early developmental milestones, develop microcephaly, and demonstrate progressive impairment of cerebral function. Hyperactivity , EEG abnormalities, and seizures, and severe learning disabilities are major clinical problems later in life. A characteristic "musty or mousy" odor on
425-504: A bath to help with atopic dermatitis. People can wear clothing designed to manage the itching, scratching and peeling. House dust mite reduction and avoidance measures have been studied in low quality trials and have not shown evidence of improving eczema. Low-quality evidence indicates that moisturizing agents ( emollients ) may reduce eczema severity and lead to fewer flares. In children, oil–based formulations appear to be better, and water–based formulations are not recommended. It
510-439: A carrier and a 25% chance the child will neither develop nor be a carrier for the disease. PKU is characterized by homozygous or compound heterozygous mutations in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine (Phe) to the amino acid tyrosine (Tyr). When PAH activity is reduced, phenylalanine accumulates and
595-454: A chronic one. There are several types of dermatitis including atopic dermatitis , contact dermatitis , stasis dermatitis and seborrhoeic dermatitis . Dermatitis symptoms vary with all different forms of the condition. Although every type of dermatitis has different symptoms, there are certain signs that are common for all of them, including redness of the skin, swelling , itching and skin lesions with sometimes oozing and scarring. Also,
680-626: A high amount of the Phe-lowering LNAAs, which constitutes about 41 g per 100 g protein and will therefore help maintain plasma Phe levels in the target range. In 2018, the FDA approved an enzyme substitute called pegvaliase which metabolizes phenylalanine. It is for adults who are poorly managed on other treatments. Tetrahydrobiopterin (BH4) (a cofactor for the oxidation of phenylalanine) when taken by mouth can reduce blood levels of this amino acid in some people. For women with PKU, it
765-412: A less severe accumulation of phenylalanine. Compared to classic PKU patients, patients with "hyperphe" have greater PAH enzyme activity and are able to tolerate larger amounts of phenylalanine in their diets. Without dietary intervention, mild HPA patients have blood Phe levels higher than those with normal PAH activity. There is currently no international consensus on the definition of mild HPA, however, it
850-508: A mutated gene for the enzyme phenylalanine hydroxylase (PAH), which converts the amino acid phenylalanine ("Phe") to other essential compounds in the body, in particular tyrosine. Tyrosine is a conditionally essential amino acid for PKU patients because without PAH it cannot be produced in the body through the breakdown of phenylalanine. PAH deficiency causes a spectrum of disorders, including classic phenylketonuria (PKU) and mild hyperphenylalaninemia (also known as "hyperphe" or "mild HPA"),
935-437: A mutated gene typically do not have symptoms. Many countries have newborn screening programs for the disease. Treatment is with a diet that (1) is low in foods that contain phenylalanine, and which (2) includes special supplements. Babies should use a special formula with a small amount of breast milk . The diet should begin as soon as possible after birth and be continued for life. People who are diagnosed early and maintain
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#17327724525931020-610: A newborn for over 100 mm genetic metabolic disorders. Because of the multiplicity of conditions, many different diagnostic tests are used for screening. An abnormal result is often followed by a subsequent "definitive test" to confirm the suspected diagnosis. Common screening tests used in the last sixty years: Specific diagnostic tests (or focused screening for a small set of disorders): A 2015 review reported that even with all these diagnostic tests, there are cases when "biochemical testing, gene sequencing, and enzymatic testing can neither confirm nor rule out an IEM, resulting in
1105-403: A problem after sunlight exposure, bringing on phototoxic dermatitis . About three-quarters of cases of contact eczema are of the irritant type, which is the most common occupational skin disease. Contact eczema is curable, provided the offending substance can be avoided and its traces removed from one's environment. (ICD-10 L23; L24; L56.1; L56.0) Seborrhoeic dermatitis or seborrheic dermatitis
1190-452: A promising and active research field. Untreated PKU can lead to intellectual disability , seizures , behavioral problems, and mental disorders . It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head , and low birth weight . Because the mother's body is able to break down phenylalanine during pregnancy, infants with PKU are normal at birth. The disease
1275-419: A rate of 1 in 10,000. Turkey has the highest documented rate in the world, with 1 in 2,600 births, while countries such as Finland and Japan have extremely low rates with fewer than one case of PKU in 100,000 births. A 1987 study from Slovakia reports a Roma population with an extremely high incidence of PKU (one case in 40 births) due to extensive inbreeding. It is the most common amino acid metabolic problem in
1360-465: A red bumpy rash around the mouth. Dermatitis herpetiformis symptoms include itching, stinging and a burning sensation. Papules and vesicles are commonly present. The small red bumps experienced in this type of dermatitis are usually about 1 cm in size, red in color and may be found symmetrically grouped or distributed on the upper or lower back, buttocks , elbows , knees, neck, shoulders and scalp . The symptoms of seborrhoeic dermatitis , on
1445-469: A result are unable to keep foreign invaders out, leading to recurring infections. If left untreated, these infections may be life-threatening, so skin barrier improvement (such as daily moisturizing to minimize transepidermal water loss ) and anti-inflammatory therapy are recommended as preventative measures. The cause of dermatitis is unknown but is presumed to be a combination of genetic and environmental factors. The hygiene hypothesis postulates that
1530-426: A set of clinical characteristics. Classification of the underlying diseases has been haphazard with numerous different classification systems, and many synonyms being used to describe the same condition. A type of dermatitis may be described by location (e.g., hand eczema ), by specific appearance (eczema craquele or discoid) or by possible cause ( varicose eczema ). Further adding to the confusion, many sources use
1615-590: A significant amount of Phe. Many fruits and vegetables are lower in Phe and can be eaten in larger quantities. Infants may still be breastfed to provide all of the benefits of breastmilk, but the quantity must also be monitored and supplementation for missing nutrients will be required. The sweetener aspartame , present in many diet foods and soft drinks, must also be avoided, as aspartame contains phenylalanine. The amino acid tyrosine becomes essential in people with phenylalanine hydroxylase deficiency. Thus, in addition to
1700-473: A strict diet can have normal health and a normal life span . Effectiveness is monitored through periodic blood tests. The medication sapropterin dihydrochloride may be useful in some. Phenylketonuria affects about 1 in 12,000 babies. Males and females are affected equally. The disease was discovered in 1934 by Ivar Asbjørn Følling , with the importance of diet determined in 1935. As of 2023, genetic therapies that aim to directly restore liver PAH activity are
1785-478: A study in British Columbia , the overall incidence of the inborn errors of metabolism were estimated to be 40 per 100,000 live births or 1 in 2,500 births, overall representing more than approximately 15% of single gene disorders in the population. While a Mexican study established an overall incidence of 3.4:1,000 live newborns and a carrier detection of 6.8:1,000 NBS. Eczema Dermatitis
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#17327724525931870-907: Is a condition sometimes classified as a form of eczema that is closely related to dandruff . It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk. In newborns, it causes a thick, yellow, crusty scalp rash called cradle cap , which seems related to lack of biotin and is often curable. (ICD-10 L21; L21.0) There is a connection between seborrheic dermatitis and Malassezia fungus, and antifungals such as anti-dandruff shampoo can be helpful in treating it. Dyshidrosis (dyshidrotic eczema, pompholyx, vesicular palmoplantar dermatitis) only occurs on palms, soles, and sides of fingers and toes. Tiny opaque bumps called vesicles , thickening, and cracks are accompanied by itching, which gets worse at night. A common type of hand eczema, it worsens in warm weather. (ICD-10 L30.1) Discoid eczema (nummular eczema, exudative eczema, microbial eczema)
1955-477: Is a peptide ensures that the absorption rate of its amino acids is prolonged compared to free amino acids and thereby results in improved protein retention and increased satiety compared to free amino acids. Another important benefit of CGMP is that the taste is significantly improved when CGMP substitutes part of the free amino acids and this may help ensure improved compliance to the PKU diet. Furthermore, CGMP contains
2040-809: Is a related disorder showing multiple lumps. (ICD-10 L28.0; L28.1) Autoeczematization (id reaction, auto sensitization) is an eczematous reaction to an infection with parasites , fungi , bacteria , or viruses . It is completely curable with the clearance of the original infection that caused it. The appearance varies depending on the cause. It always occurs some distance away from the original infection. (ICD-10 L30.2) There are eczemas overlaid by viral infections ( eczema herpeticum or vaccinatum ), and eczemas resulting from underlying disease (e.g., lymphoma ). Eczemas originating from ingestion of medications, foods, and chemicals, have not yet been clearly systematized. Other rare eczematous disorders exist in addition to those listed here. There have been various studies on
2125-475: Is a term used for different types of skin inflammation, typically characterized by itchiness , redness and a rash . In cases of short duration, there may be small blisters , while in long-term cases the skin may become thickened . The area of skin involved can vary from small to covering the entire body. Dermatitis is also called eczema but the same term is often used for the most common type of skin inflammation, atopic dermatitis . The exact cause of
2210-407: Is an autosomal recessive metabolic genetic disorder . As an autosomal recessive disorder, two PKU alleles are required for an individual to experience symptoms of the disease. For a child to inherit PKU, both parents must have and pass on the defective gene. If both parents are carriers for PKU, there is a 25% chance any child they have will be born with the disorder, a 50% chance the child will be
2295-597: Is an inherited genetic disorder. It is caused by mutations in the PAH gene, which can result in inefficient or nonfunctional phenylalanine hydroxylase , an enzyme responsible for the metabolism of excess phenylalanine. This results in the buildup of dietary phenylalanine to potentially toxic levels. It is autosomal recessive , meaning that both copies of the gene must be mutated for the condition to develop. There are two main types, classic PKU and variant PKU, depending on whether any enzyme function remains. Those with one copy of
2380-401: Is an important part of the treatment for patients with classic PKU. Evidence supports dietary supplementation with large neutral amino acids (LNAAs). The LNAAs (e.g. leu , tyr , trp , met , his , ile , val , thr ) may compete with phe for specific carrier proteins that transport LNAAs across the intestinal mucosa into the blood and across the blood–brain barrier into the brain. Its use
2465-428: Is characterized by round spots of oozing or dry rash, with clear boundaries, often on lower legs. It is usually worse in winter. The cause is unknown, and the condition tends to come and go. (ICD-10 L30.0) Venous eczema (gravitational eczema, stasis dermatitis, varicose eczema) occurs in people with impaired circulation, varicose veins , and edema , and is particularly common in the ankle area of people over 50. There
2550-462: Is common, especially among people with certain occupations; exact rates are unclear. The terms dermatitis and eczema are sometimes used synonymously. However the term eczema is often used to specifically mean atopic dermatitis (also known as atopic eczema). Terminology might also differ according to countries. In some languages, dermatitis and eczema mean the same thing, while in other languages dermatitis implies an acute condition and eczema
2635-425: Is converted into phenylpyruvate (also known as phenylketone), which can be detected in the urine . Carriers of a single PKU allele do not exhibit symptoms of the disease but appear to be protected to some extent against the fungal toxin ochratoxin A . Louis Woolf suggested that this accounted for the persistence of the allele in certain populations, in that it confers a selective advantage —in other words, being
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2720-708: Is important for the health of their children to maintain low Phe levels before and during pregnancy. Though the developing fetus may only be a carrier of the PKU gene, the intrauterine environment can have very high levels of phenylalanine, which can cross the placenta. The child may develop congenital heart disease, growth retardation, microcephaly and intellectual disability as a result. PKU-affected women themselves are not at risk of additional complications during pregnancy. In most countries, women with PKU who wish to have children are advised to lower their blood Phe levels (typically to between 2 and 6 mg/dL) before they become pregnant, and carefully control their levels throughout
2805-430: Is insufficient to recommend its use. There is moderate certainty evidence that the use of skin care interventions such as emollients within the first year of life of an infant's life is not effective in preventing eczema. In fact, it may increase the risk of skin infection and of unwanted effects such as allergic reaction to certain moisturizers and a stinging sensation. There has not been adequate evaluation of changing
2890-492: Is limited in the US due to the cost but is available in most countries as part of a low protein / PHE diet to replace missing nutrients. Another treatment strategy is casein glycomacropeptide (CGMP), which is a milk peptide naturally free of Phe in its pure form CGMP can substitute for the main part of the free amino acids in the PKU diet and provides several beneficial nutritional effects compared to free amino acids. The fact that CGMP
2975-408: Is most frequently diagnosed at blood Phe levels between 2–6 mg/dL. Phenylalanine is a large, neutral amino acid (LNAA). LNAAs compete for transport across the blood–brain barrier (BBB) via the large neutral amino acid transporter (LNAAT). If phenylalanine is in excess in the blood, it will saturate the transporter. Excessive levels of phenylalanine tend to decrease the levels of other LNAAs in
3060-414: Is necessary for proper activity of the enzyme PAH, and this coenzyme can be supplemented as treatment. Those with this form of hyperphenylalaninemia may have a deficiency of tyrosine (which is created from phenylalanine by PAH), in which case treatment is supplementation of tyrosine to account for this deficiency. Levels of dopamine can be used to distinguish between these two types. Tetrahydrobiopterin
3145-402: Is not detectable by physical examination at that time, because no damage has yet been done. Newborn screening is performed to detect the disease and initiate treatment before any damage is done. The blood sample is usually taken by a heel prick , typically performed 2–7 days after birth. This test can reveal elevated phenylalanine levels after one or two days of normal infant feeding. If a child
3230-431: Is not diagnosed during the routine newborn screening test and a phenylalanine-restricted diet is not introduced, then phenylalanine levels in the blood will increase over time. Toxic levels of phenylalanine (and insufficient levels of tyrosine ) can interfere with infant development in ways that have permanent effects. The disease may present clinically with seizures , hypopigmentation (excessively fair hair and skin), and
3315-411: Is not supplemented with other amino acids. Classic PKU affects myelination and white matter tracts in untreated infants; this may be one major cause of neurological problems associated with phenylketonuria. Differences in white matter development are observable with magnetic resonance imaging . Abnormalities in gray matter can also be detected, particularly in the motor and pre-motor cortex, thalamus and
3400-503: Is redness, scaling, darkening of the skin, and itching. The disorder predisposes to leg ulcers . (ICD-10 I83.1) Dermatitis herpetiformis (Duhring's disease) causes an intensely itchy and typically symmetrical rash on arms, thighs, knees, and back. It is directly related to celiac disease , can often be put into remission with an appropriate diet, and tends to get worse at night. (ICD-10 L13.0) Hyperkeratotic hand dermatitis presents with hyperkeratotic, fissure-prone, erythematous areas of
3485-648: Is required for appropriate growth, but levels must be strictly controlled. Optimal health ranges (or "target ranges") are between 120 and 360 μmol/L or equivalently 2 to 6 mg/dL. This is optimally to be achieved during at least the first 10 years, to allow the brain to develop normally. The diet requires restricting or eliminating foods high in Phe, such as soybeans , egg whites , shrimp , chicken breast , spirulina , watercress , fish , nuts , crayfish , lobster , tuna , turkey , legumes , and lowfat cottage cheese . Starchy foods, such as potatoes and corn are generally acceptable in controlled amounts, but
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3570-486: Is required to convert Phe to Tyr and is required to convert Tyr to L-DOPA via the enzyme tyrosine hydroxylase . L-DOPA, in turn, is converted to dopamine . Low levels of dopamine lead to high levels of prolactin . By contrast, in classical PKU (without dihydrobiopterin involvement), prolactin levels would be relatively normal. As of 2020, tetrahydrobiopterin deficiency was known to result from defects in five genes. The enzyme phenylalanine hydroxylase normally converts
3655-464: Is sometimes misdiagnosed as atopic dermatitis. Stress can cause atopic dermatitis to worsen. Contact dermatitis is of two types: allergic (resulting from a delayed reaction to an allergen , such as poison ivy , nickel , or Balsam of Peru ), and irritant (resulting from direct reaction to a detergent, such as sodium lauryl sulfate , for example). Some substances act both as allergen and irritants (wet cement, for example). Other substances cause
3740-426: Is treated by avoiding what is causing it. Seborrheic dermatitis is treated with antifungals such as anti-dandruff shampoo . Bathing once or more a day is recommended, usually for five to ten minutes in warm water. Soaps should be avoided, as they tend to strip the skin of natural oils and lead to excessive dryness. The American Academy of Dermatology suggests using a controlled amount of bleach diluted in
3825-481: Is unclear if moisturizers that contain ceramides are more or less effective than others. Products that contain dyes, perfumes, or peanuts should not be used. Occlusive dressings at night may be useful. Some moisturizers or barrier creams may reduce irritation in occupational irritant hand dermatitis, a skin disease that can affect people in jobs that regularly come into contact with water, detergents , chemicals or other irritants. Some emollients may reduce
3910-433: Is usually more painful than itchy. Although the symptoms of atopic dermatitis vary from person to person, the most common symptoms are dry, itchy, red skin, on light skin. However, this redness does not appear on darker skin and dermatitis can appear darker brown or purple in color. Typical affected skin areas include the folds of the arms, the back of the knees , wrists, face and hands . Perioral dermatitis refers to
3995-441: The amino acid phenylalanine into the amino acid tyrosine . If this reaction does not take place, phenylalanine accumulates and tyrosine is deficient. Excessive phenylalanine can be metabolized into phenylketones through the minor route, a transaminase pathway with glutamate . Metabolites include phenylacetate , phenylpyruvate and phenethylamine . Elevated levels of phenylalanine in the blood and detection of phenylketones in
4080-674: The excrement from house dust mites , with up to 5% of people showing antibodies to the mites, the overall role this plays awaits further corroboration. Essential fatty acid deficiency results in a dermatitis similar to that seen in zinc or biotin deficiency . A number of genes have been associated with eczema, one of which affects production of filaggrin . Genome-wide studies found three new genetic variants associated with eczema: OVOL1, ACTL9 and IL4-KIF3A. Eczema occurs about three times more frequently in individuals with celiac disease and about two times more frequently in relatives of those with celiac disease, potentially indicating
4165-408: The 1950s Arild Hansen showed that infants fed skimmed milk developed essential fatty acid deficiency which was characterized by an increased food intake, poor growth, and a scaly dermatitis, and was cured by the administration of corn oil . There is no known cure for some types of dermatitis, with treatment aiming to control symptoms by reducing inflammation and relieving itching. Contact dermatitis
4250-576: The United Kingdom. Before the causes of PKU were understood, PKU caused severe disability in most people who inherited the relevant mutations. Nobel and Pulitzer Prize winning author Pearl S. Buck had a daughter named Carol who lived with PKU before treatment was available, and wrote an account of its effects in a book called The Child Who Never Grew. Many untreated PKU patients born before widespread newborn screening are still alive, largely in dependent living homes/institutions. Phenylketonuria
4335-586: The allergen or irritant. Antihistamines may help with sleep and decrease nighttime scratching. Dermatitis was estimated to affect 245 million people globally in 2015, or 3.34% of the world population. Atopic dermatitis is the most common type and generally starts in childhood. In the United States, it affects about 10–30% of people. Contact dermatitis is twice as common in females as in males. Allergic contact dermatitis affects about 7% of people at some point in their lives. Irritant contact dermatitis
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#17327724525934420-417: The amino acids and other necessary nutrients that would otherwise be lacking in a low-phenylalanine diet. Tyrosine, which is normally derived from phenylalanine and which is necessary for normal brain function, is usually supplemented. Consumption of the protein substitute formulas can actually reduce phenylalanine levels, probably because it stops the process of protein catabolism from releasing Phe stored in
4505-443: The area of the skin on which the symptoms appear tends to be different with every type of dermatitis, whether on the neck , wrist , forearm , thigh or ankle . Although the location may vary, the primary symptom of this condition is itchy skin. More rarely, it may appear on the genital area , such as the vulva or scrotum . Symptoms of this type of dermatitis may be very intense and may come and go. Irritant contact dermatitis
4590-522: The blood, which is toxic to the brain. If left untreated (and often even in treatment), complications of PKU include severe intellectual disability, brain function abnormalities, microcephaly, mood disorders, irregular motor functioning, and behavioral problems such as attention deficit hyperactivity disorder , as well as physical symptoms such as a "musty" odor, eczema, and unusually light skin and hair coloration. Classical PKU, and its less severe forms "mild PKU" and "mild hyperphenylalaninemia" are caused by
4675-412: The brain. As these amino acids are necessary for protein and neurotransmitter synthesis, Phe buildup hinders the development of the brain , causing intellectual disability . Recent research suggests that neurocognitive, psychosocial, quality of life, growth, nutrition, bone pathology are slightly suboptimal even for patients who are treated and maintain their Phe levels in the target range, if their diet
4760-399: The careful reduction of Phe in the diet, Tyr must be supplemented to ensure that nutritional needs are met. Different people can tolerate different amounts of Phe in their diet. Regular blood tests are used to determine the effects of dietary Phe intake on blood Phe level. Supplementary "protein substitute" formulas are typically prescribed for people PKU (starting in infancy) to provide
4845-620: The cause of asthma , eczema, and other allergic diseases is an unusually clean environment in childhood which leads to an insufficient human microbiota . It is supported by epidemiologic studies for asthma. The hypothesis states that exposure to bacteria and other immune system modulators is important during development, and missing out on this exposure increases the risk for asthma and allergy. One systematic review of literature on eczema found that urban areas have an increased prevalence of eczema compared to rural areas. While it has been suggested that eczema may sometimes be an allergic reaction to
4930-417: The child is likely to develop permanent intellectual disability, even if dietary interventions begin shortly thereafter. People who follow the prescribed dietary treatment from birth may (but not always) have no symptoms. Their PKU would be detectable only by a blood test. People must adhere to a special diet low in Phe for optimal brain development. Since Phe is necessary for the synthesis of many proteins, it
5015-399: The concentration of Phe and the ratio of Phe to tyrosine , the ratio will be elevated in PKU. PKU is not curable. However, if it is diagnosed early enough, an affected newborn can grow up with normal brain development by managing and controlling phenylalanine ("Phe") levels through diet, or a combination of diet and medication. If dietary treatment is not initiated within 2 weeks after birth,
5100-412: The condition is often unclear. Cases may involve a combination of allergy and poor venous return . The type of dermatitis is generally determined by the person's history and the location of the rash. For example, irritant dermatitis often occurs on the hands of those who frequently get them wet. Allergic contact dermatitis occurs upon exposure to an allergen , causing a hypersensitivity reaction in
5185-478: The diet to reduce eczema. There is some evidence that infants with an established egg allergy may have a reduction in symptoms if eggs are eliminated from their diets. Benefits have not been shown for other elimination diets, though the studies are small and poorly executed. Establishing that there is a food allergy before dietary change could avoid unnecessary lifestyle changes. Oils with fatty acids that have been studied to prevent dermatitis include: In
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#17327724525935270-529: The end of the pregnancy, as a result. When maternal blood Phe levels fall below 2 mg/dL, anecdotal reports indicate that the mothers may experience adverse effects, including headaches, nausea, hair loss, and general malaise. When low phenylalanine levels are maintained for the duration of pregnancy, there are no elevated levels of risk of birth defects compared with a baby born to a non-PKU mother. The average number of new cases of PKU varies in different human populations. United States Caucasians are affected at
5355-616: The enormous number of these diseases and the numerous systems negatively impacted, nearly every "presenting complaint" to a healthcare provider may have a congenital metabolic disease as a possible cause, especially in childhood and adolescence. The following are examples of potential manifestations affecting each of the major organ systems. Dozens of congenital metabolic diseases are now detectable by newborn screening tests, especially expanded testing using mass spectrometry. Gas chromatography–mass spectrometry -based technology with an integrated analytics system has now made it possible to test
5440-469: The epidermis, papillary dermis, and superficial vascular plexus) can basically be classified into either of the following groups: Atopic dermatitis is an allergic disease believed to have a hereditary component and often runs in families whose members have asthma . Itchy rash is particularly noticeable on the head and scalp, neck, inside of elbows, behind knees, and buttocks. It is very common in developed countries and rising. Irritant contact dermatitis
5525-445: The hippocampus. It was recently suggested that PKU may resemble amyloid diseases, such as Alzheimer's disease and Parkinson's disease, due to the formation of toxic amyloid-like assemblies of phenylalanine. A rarer form of hyperphenylalaninemia is tetrahydrobiopterin deficiency , which occurs when the PAH enzyme is normal, and a defect is found in the biosynthesis or recycling of the cofactor tetrahydrobiopterin (BH 4 ). BH 4
5610-433: The inherited metabolic diseases were classified as disorders of carbohydrate metabolism, amino acid metabolism, organic acid metabolism, or lysosomal storage diseases . In recent decades, hundreds of new inherited disorders of metabolism have been discovered and the categories have proliferated. Following are some of the major classes of congenital metabolic diseases, with prominent examples of each class. Because of
5695-407: The middle or proximal palm, and the volar surfaces of the fingers may also be involved. Neurodermatitis ( lichen simplex chronicus , localized scratch dermatitis) is an itchy area of thickened, pigmented eczema patch that results from habitual rubbing and scratching. Usually, there is only one spot. Often curable through behaviour modification and anti-inflammatory medication. Prurigo nodularis
5780-411: The muscles and other tissues into the blood. Many PKU patients have their highest Phe levels after a period of fasting (such as overnight) because fasting triggers catabolism. A diet that is low in phenylalanine but does not include protein substitutes may also fail to lower blood Phe levels, since a nutritionally insufficient diet may also trigger catabolism. For all these reasons, the prescription formula
5865-462: The need to rely on the patient's clinical course". A 2021 review showed that several neurometabolic disorders converge on common neurochemical mechanisms that interfere with biological mechanisms also considered central in ADHD pathophysiology and treatment. This highlights the importance of close collaboration between health services to avoid clinical overshadowing . In the middle of the 20th century
5950-557: The newborn screening test for PKU in the early 1960s. With the knowledge that PKU could be detected before symptoms were evident, and treatment initiated, screening was quickly adopted around the world. Ireland was the first country to introduce a national screening programme in February 1966, Austria also started screening in 1966 and England in 1968. In 2017, the European Guidelines were published. They were called for by
6035-465: The nose, on the chest , and on the upper back. People with eczema should not receive the smallpox vaccination due to risk of developing eczema vaccinatum , a potentially severe and sometimes fatal complication. Other major health risks for people with dermatitis are viral and bacterial infections because atopic dermatitis patients have deficiencies in their proteins and lipids that have barrier functions along with defects in dendritic cells and as
6120-409: The other hand, tend to appear gradually, from dry or greasy scaling of the scalp ( dandruff ) to scaling of facial areas, sometimes with itching, but without hair loss . In newborns , the condition causes a thick and yellowish scalp rash, often accompanied by a diaper rash . In severe cases, symptoms may appear along the hairline, behind the ears, on the eyebrows , on the bridge of the nose , around
6205-584: The patient organizations such as the European Society for Phenylketonuria and Allied Disorders Treated as Phenylketonuria . They have received some critical reception. The word phenylketonuria uses combining forms of phenyl + ketone + -uria ; it is pronounced / ˌ f iː n aɪ l ˌ k iː t ə ˈ nj ʊər i ə , ˌ f ɛ n -, - n ɪ l -, - n əl -, - t oʊ -/ . Other therapies are under investigation, including gene therapy . Inborn error of metabolism Traditionally
6290-443: The pregnancy. This is achieved by performing regular blood tests and adhering very strictly to a diet, in general monitored on a day-to-day basis by a specialist metabolic dietitian. In many cases, as the fetus' liver begins to develop and produce PAH normally, the mother's blood Phe levels will drop, requiring an increased intake to remain within the safe range of 2–6 mg/dL. The mother's daily Phe intake may double or even triple by
6375-447: The prevention of dermatitis through diet, none of which have proven any positive effect. Exclusive breastfeeding of infants during at least the first few months may decrease the risk. There is no good evidence that a mother's diet during pregnancy or breastfeeding affects the risk, nor is there evidence that delayed introduction of certain foods is useful. There is tentative evidence that probiotics in infancy may reduce rates but it
6460-404: The principal treatment for some of the amino acid disorders was restriction of dietary protein and all other care was simply management of complications. In the past twenty years, new medications, enzyme replacement, gene therapy, and organ transplantation have become available and beneficial for many previously untreatable disorders. Some of the more common or promising therapies are listed: In
6545-506: The quantity of Phe consumed from these foods must be monitored. A corn-free diet may be prescribed in some cases. A food diary is usually kept to record the amount of Phe consumed with each meal, snack, or drink. An "exchange" system can be used to calculate the amount of Phe in a portion of food from the protein content identified on a nutritional information label. Lower-protein "medical food" substitutes are often used in place of normal bread , pasta , and other grain-based foods, which contain
6630-1133: The skin, as well as a predisposition for eczema , persist throughout life in the absence of treatment. The damage done to the brain if PKU is untreated during the first months of life is not reversible. It is critical to control the diet of infants with PKU very carefully so that the brain has an opportunity to develop normally. Affected children who are detected at birth and treated are much less likely to develop neurological problems or have seizures and intellectual disability (though such clinical disorders are still possible including asthma, eczema, anemia, weight gain, renal insufficiency, osteoporosis, gastritis, esophagus, and kidney deficiencies, kidney stones, and hypertension). Additionally, major depressive disorders occur 230% higher than controls; dizziness and giddiness occur 180% higher; chronic ischemic heart disease, asthma, diabetes, and gastroenteritis occur 170% higher; and stress and adjustment disorders occur 160% higher. In general, however, outcomes for people treated for PKU are good. Treated people may have no detectable physical, neurological, or developmental problems at all. PKU
6715-408: The skin. Prevention of atopic dermatitis is typically with essential fatty acids , and may be treated with moisturizers and steroid creams. The steroid creams should generally be of mid-to high strength and used for less than two weeks at a time, as side effects can occur. Antibiotics may be required if there are signs of skin infection . Contact dermatitis is typically treated by avoiding
6800-406: The term eczema interchangeably for the most common type: atopic dermatitis . The European Academy of Allergology and Clinical Immunology (EAACI) published a position paper in 2001, which simplifies the nomenclature of allergy-related diseases, including atopic and allergic contact eczemas. Non-allergic eczemas are not affected by this proposal. By histopathology , superficial dermatitis (in
6885-587: The urine is diagnostic, however most patients are diagnosed via newborn screening. PKU is commonly included in the newborn screening panel of many countries, with varied detection techniques. Most babies born in Europe, North America, and Australia are screened for PKU soon after birth. Screening for PKU is done with bacterial inhibition assay ( Guthrie test ), immunoassays using fluorometric or photometric detection, or amino acid measurement using tandem mass spectrometry (MS/MS). Measurements done using MS/MS determine
6970-405: The urine of other affected patients. This led to the discovery of the same substance he had found in eight other patients. He conducted tests and found reactions that gave rise to benzaldehyde and benzoic acid , which led him to conclude that the compound contained a benzene ring. Further testing showed the melting point to be the same as phenylpyruvic acid , which indicated that the substance
7055-466: Was about a year old, the mother noticed a strong smell to his urine. Følling obtained urine samples from the children and, after many tests, he found that the substance causing the odor in the urine was phenylpyruvic acid. The children, he concluded, had excess phenylpyruvic acid in the urine, the condition which came to be called phenylketonuria (PKU). His analysis of the urine of the two affected siblings led him to request many physicians near Oslo to test
7140-608: Was discovered by the Norwegian physician Ivar Asbjørn Følling in 1934 when he noticed hyperphenylalaninemia (HPA) was associated with intellectual disability. In Norway, this disorder is known as Følling's disease, named after its discoverer. Følling was one of the first physicians to apply detailed chemical analysis to the study of disease. In 1934 at Rikshospitalet , Følling saw a young woman named Borgny Egeland. She had two children, Liv and Dag, who had been normal at birth but subsequently developed intellectual disability. When Dag
7225-478: Was in the urine. In 1954, Horst Bickel , Evelyn Hickmans and John Gerrard published a paper that described how they created a diet that was low in phenylalanine and the patient recovered. Bickel, Gerrard and Hickmans were awarded the John Scott Medal in 1962 for their discovery. PKU was the first disorder to be routinely diagnosed through widespread newborn screening . Robert Guthrie introduced
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