Disorders of Amino
Acid Metabolism


Amino acids are the building blocks of proteins and
have many functions in the body. Hereditary disorders of amino acid
processing can result from defects either in the breakdown of amino
acids or in the body's ability to get amino acids into cells. Because
these disorders cause symptoms early in life, newborns are routinely
screened for several common ones. In the United States, newborns are
commonly screened for phenylketonuria, maple syrup disease,
homocystinuria, tyrosinemia, and a number of other inherited disorders,
although screening varies from state to state.



Phenylketonuria (PKU)




Phenylketonuria
occurs in infants born without the ability to normally break down
an amino acid called phenylalanine. This disorder causes phenylalanine,
which is toxic to the brain, to build up in the .

• Phenylketonuria is caused by lack of the enzyme needed to convert phenylalanine to tyrosine.
  
• Symptoms include intellectual disability, seizures, nausea, vomiting, an eczema-like rash, and a mousy body odor.
  
• The diagnosis is based on a test.
  
• A strict phenylalanine-restricted diet allows for normal growth and development.
  

Phenylketonuria (PKU) is a disorder that causes a
buildup of the amino acid phenylalanine, which is an essential amino
acid that cannot be synthesized in the body but is present in food.
Excess phenylalanine is normally converted to tyrosine, another amino
acid, and eliminated from the body. Without the enzyme that converts it
to tyrosine, phenylalanine builds up in the and is toxic to the
brain, causing intellectual disability.



Symptoms



Newborns with PKU rarely have symptoms right away,
although sometimes they are sleepy or eat poorly. If not treated,
affected infants progressively develop intellectual disability over the
first few years of life, and it eventually becomes severe. Other
symptoms include seizures, nausea and vomiting, an eczema-like rash,
lighter skin and hair than their family members, aggressive or
self-injurious behavior, hyperactivity, and sometimes psychiatric
symptoms. Untreated children often give off a mousy body and odor
as a result of a by-product of phenylalanine (phenylacetic acid) in
their and sweat.



Diagnosis



PKU is usually diagnosed with a routine screening test.



PKU occurs in most ethnic groups. If PKU runs in the
family and DNA is available from an affected family member,
amniocentesis or chorionic villus sampling with DNA analysis can be
done to determine whether a fetus has the disorder.



Parents and siblings of children with PKU can be
tested to find out whether they carry the gene that causes the disease.
If two carriers conceive a child, that child has a 1 in 4 chance of
being born with the disease.



Prognosis



A phenylalanine-restricted diet, if started early and
maintained well, allows for normal development. However, if very strict
control of the diet is not maintained, affected children may begin to
have difficulties in school. Dietary restrictions started after 2 to 3
years of age may control extreme hyperactivity and seizures and raise
the child's eventual intelligence quotient (IQ) but do not reverse
intellectual disability. Recent evidence suggests that some
intellectually disabled s with PKU (born before newborn screening
tests were available) may function better when they follow the PKU diet.



A phenylalanine-restricted diet should continue for
life, or intelligence may decrease and neurologic and psychiatric
problems may ensue.



Prevention
and Treatment



To prevent intellectual disability, people must
restrict phenylalanine intake (but not eliminate it altogether because
people need some phenylalanine to live) beginning in the first few
weeks of life. Because all natural sources of protein contain too much
phenylalanine for children with PKU, affected children cannot have
meat, milk, or other common foods that contain protein. Instead, they
must eat a variety of phenylalanine-free processed foods, which are
specially manufactured. Low-protein natural foods, such as fruits,
vegetables, and restricted amounts of certain grain cereals, can be
eaten. Special nutritional products, including infant formula without
phenylalanine, are also available. Future treatments may include cell
transplantation and gene therapy.



Maple
Syrup Disease




Maple syrup
urine disease is caused by lack of the enzyme needed to metabolize
amino acids. By-products of these amino acids cause the to
smell like maple syrup.




Children with maple syrup disease are unable to
metabolize certain amino acids. By-products of these amino acids build
up, causing neurologic changes, including seizures and intellectual
disability. These by-products also cause body fluids, such as and
sweat, to smell like maple syrup. This disease is most common among
Mennonite families.



There are many forms of maple syrup disease. In
the most severe form, infants develop neurologic abnormalities,
including seizures and coma, during the first week of life and can die
within days to weeks. In the milder forms, children initially appear
normal but during infection, surgery, or other physical stress, they
can develop vomiting, staggering, confusion, and coma.



Since 2007, nearly every state in the United States has screened all newborns for maple syrup disease with a test.



Infants with severe disease are treated with dialysis (see [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذا الرابط]). Some children with mild disease benefit from injections of vitamin B₁
(thiamin). After the disease has been brought under control, children
must always consume a special artificial diet that is low in three
amino acids (leucine, isoleucine, and valine). During times of physical
stress or flare-ups, it may be necessary to monitor tests and
give fluids by vein.



Homocystinuria




Homocystinuria
is caused by lack of the enzyme needed to metabolize homocysteine. This
disorder can cause a number of symptoms, including decreased vision
and skeletal abnormalities.




Children with homocystinuria are unable to metabolize
the amino acid homocysteine, which, along with certain toxic
by-products, builds up to cause a variety of symptoms. Symptoms may be
mild or severe, depending on the particular enzyme defect.



Infants with this disorder are normal at birth. The
first symptoms, including dislocation of the lens of the eye, causing
severely decreased vision, usually begin after 3 years of age. Most
children have skeletal abnormalities, including osteoporosis. Children
are usually tall and thin with a curved spine, chest deformities,
elongated limbs, and long, spiderlike fingers. Without early diagnosis
and treatment, psychiatric and behavioral disorders and intellectual
disability are common. Homocystinuria makes the more likely to
clot spontaneously, resulting in strokes, high pressure, and many
other serious problems.



Since 2008, nearly every state in the United States
has screened all newborns for homocystinuria with a test. The
diagnosis is confirmed by a test measuring enzyme function in liver or
skin cells.



Some children with homocystinuria improve when given vitamin B₆ (pyridoxine) or vitamin B₁₂ (cobalamin).



Tyrosinemia



Tyrosinemia is caused by lack of the enzyme needed to
metabolize tyrosine. The most common form of this disorder mostly
affects the liver and the kidneys.



Children with tyrosinemia are unable to completely
metabolize the amino acid tyrosine. By-products of this amino acid
build up, causing a variety of symptoms. In some states, the disorder
is detected with newborn screening tests.



There are two main types of tyrosinemia: type I and type II.




Type I tyrosinemia is most common among children of
French-Canadian or Scandinavian descent. Children with this disorder
typically become ill sometime within the first year of life with
dysfunction of the liver, kidneys, and nerves, resulting in
irritability, rickets, or even liver failure and . Restriction of
tyrosine in the diet is of little help. An experimental , which
blocks production of toxic metabolites, may help children with type I
tyrosinemia. Often, children with type I tyrosinemia require a liver
transplant. Since 2007, nearly every state in the United States has
screened all newborns for type I tyrosinemia with a test.




Type II tyrosinemia is less common. Affected children sometimes
have intellectual disability and frequently develop sores on the skin
and eyes. Unlike type I tyrosinemia, restriction of tyrosine in the
diet can prevent problems from developing.

List of amino acid metabolism disorders






Several [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذا الرابط] cause errors in amino acid metabolism. [ندعوك للتسجيل في المنتدى أو التعريف بنفسك لمعاينة هذا الرابط]
metabolism disorders result from defects either in the synthesis of or
the breakdown of amino acids or in the body's ability to get the amino
acids into cells. These disrders can be screened for by analysis of the
amino acid content of . This screen is known as aminoaciduria.

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