Overview of some inborn errors of metabolism along with dietary management.

1. Inborn errors of Metabolism
BY: AKANSHA BHATNAGAR

2. Introduction
• Inborn errors of metabolism are rare genetic
(inherited) disorders in which the body cannot
properly turn food into energy. The disorders are
usually caused by defects in specific proteins
(enzymes) that help break down (metabolize)
parts of food.
• A food product that is not broken down into
energy can build up in the body and cause a wide
range of symptoms. Several inborn errors of
metabolism cause developmental delays or other
medical problems if they are not controlled.

3. Garrod
Hypothesis
The one gene-one enzyme hypothesis was first proposed
by the English physician Archibald Garrod in 1909. It
suggests that each gene codes for a single,
specific enzyme. In other words, under this hypothesis,
each gene would be responsible for the enzyme
facilitating a single step in a metabolic process and the
inherited disorders result from reduced activity or
complete absence of enzymes involved in certain
biochemical pathways.

4. GALACTOSEMIA
• Galactosemia is a family of genetic disorders that result from compromised
ability to metabolize the sugar galactose; the term “galactosemia” literally
means too much galactose in the blood. The different types of galactosemia
include:
 Classic and clinical variant galactosemia (aka Type 1 galactosemia)
 Duarte variant galactosemia
 Galactokinase deficiency (aka Type 2 galactosemia)
 Epimerase deficiency (aka Type 3 galactosemia)
• Galactosemia prevents a person from processing the sugar galactose, which
is found in many foods. Galactose also exists as part of another sugar,
lactose, found in all dairy products.
• Normally when a person consumes a product that contains lactose, the
body breaks the lactose down into galactose and glucose. In Galactosemia
galactose builds up in the blood. This accumulation of galactose can cause
serious complications such as:
 an enlarged liver
 kidney failure
 cataracts in the eyes
 brain damage.

7. PHENYLKETONURIA (PKU)
• Phenylketonuria (commonly known as PKU) is an inherited disorder that
increases the levels of a substance called phenylalanine in the blood.
Phenylalanine is a building block of proteins (an amino acid) that is obtained
through the diet. It is found in all proteins and in some artificial sweeteners. If
PKU is not treated, phenylalanine can build up to harmful levels in the body,
causing intellectual disability and other serious health problems.
• The signs and symptoms of PKU vary from mild to severe. The most severe form
of this disorder is known as classic PKU. Infants with classic PKU appear normal
until they are a few months old. Without treatment, these children develop
permanent intellectual disability. Seizures, delayed development, behavioral
problems, and psychiatric disorders are also common. Untreated individuals
may have a musty or mouse-like odor as a side effect of excess phenylalanine in
the body. Children with classic PKU tend to have lighter skin and hair than
unaffected family members and are also likely to have skin disorders such as
eczema.
• Less severe forms of this condition, sometimes called variant PKU and non-PKU
hyperphenylalaninemia, have a smaller risk of brain damage. People with very
mild cases may not require treatment with a low-phenylalanine diet.

10. TYROSINEMIA
• Tyrosinemia is a genetic disorder characterized by disruptions in the
multistep process that breaks down the amino acid tyrosine, a building block
of most proteins. If untreated, tyrosine and its byproducts build up in tissues
and organs, which can lead to serious health problems.
• There are three types of tyrosinemia, which are each distinguished by their
symptoms and genetic cause. Tyrosinemia type I, the most severe form of
this disorder, is characterized by signs and symptoms that begin in the first
few months of life. Affected infants fail to gain weight and grow at the
expected rate (failure to thrive) due to poor food tolerance because high-
protein foods lead to diarrhea and vomiting.
• Tyrosinemia type II can affect the eyes, skin, and mental development. Signs
and symptoms often begin in early childhood and include eye pain and
redness, excessive tearing, abnormal sensitivity to light (photophobia), and
thick, painful skin on the palms of their hands and soles of their feet
(palmoplantar hyperkeratosis).
• Tyrosinemia type III is the rarest of the three types. The characteristic
features of this type include intellectual disability, seizures, and periodic loss
of balance and coordination (intermittent ataxia).

12. Maple Syrup Urine Disease (MSUD)
• Maple syrup urine disease is an inherited disorder in which the body is
unable to process certain protein building blocks (leucine, isoleucine
and valine) properly. The condition gets its name from the distinctive
sweet odor of affected infants' urine. It is also characterized by poor
feeding, vomiting, lack of energy (lethargy), abnormal movements,
and delayed development. If untreated, maple syrup urine disease can
lead to seizures, coma, and death.
• Maple syrup urine disease is often classified by its pattern of signs and
symptoms. The most common and severe form of the disease is the
classic type, which becomes apparent soon after birth. Variant forms
of the disorder become apparent later in infancy or childhood and are
typically milder, but they still lead to delayed development and other
health problems if not treated.
• Special feeds containing energy and proteins without the branched
chain amino acids can be give to the infants.

14. HOMOCYTINURIA
• Homocystinuria is an inherited disorder in which the body is unable to
process certain building blocks of proteins (amino acids) properly. There are
multiple forms of homocystinuria, which are distinguished by their signs and
symptoms and genetic cause. The most common form of homocystinuria is
characterized by nearsightedness (myopia), dislocation of the lens at the
front of the eye, an increased risk of abnormal blood clotting, and brittle
bones that are prone to fracture (osteoporosis) or other skeletal
abnormalities. Some affected individuals also have developmental delay and
learning problems.
• Less common forms of homocystinuria can cause intellectual disability,
failure to grow and gain weight at the expected rate (failure to thrive),
seizures, problems with movement, and a blood disorder
called megaloblastic anemia. Megaloblastic anemia occurs when a person
has a low number of red blood cells (anemia), and the remaining red blood
cells are larger than normal (megaloblastic).
• The signs and symptoms of homocystinuria typically develop within the first
year of life, although some mildly affected people may not develop features
until later in childhood or adulthood.

16. GALACTOSEMIA
• Galactosemia is a disorder that affects how the body processes a simple sugar
called galactose. A small amount of galactose is present in many foods. It is
primarily part of a larger sugar called lactose, which is found in all dairy products
and many baby formulas. The signs and symptoms of galactosemia result from
an inability to use galactose to produce energy.
• Researchers have identified several types of galactosemia. These conditions are
each caused by mutations in a particular gene and affect different enzymes
involved in breaking down galactose.
• Classic galactosemia, also known as type I, is the most common and most severe
form of the condition. If infants with classic galactosemia are not treated
promptly with a low-galactose diet, life-threatening complications appear within
a few days after birth. Affected infants typically develop feeding difficulties, a
lack of energy (lethargy), a failure to gain weight and grow as expected (failure
to thrive), yellowing of the skin and whites of the eyes (jaundice), liver damage,
and abnormal bleeding. Other serious complications of this condition can
include overwhelming bacterial infections (sepsis) and shock. Affected children
are also at increased risk of delayed development, clouding of the lens of the
eye (cataract), speech difficulties, and intellectual disability. Females with
classic galactosemia may develop reproductive problems caused by an early loss
of function of the ovaries (premature ovarian insufficiency).

17. • Galactosemia type II (also called galactokinase
deficiency) and type III (also called galactose
epimerase deficiency) cause different patterns of
signs and symptoms. Galactosemia type II causes
fewer medical problems than the classic type.
Affected infants develop cataracts but otherwise
experience few long-term complications. The
signs and symptoms of galactosemia type III vary
from mild to severe and can include cataracts,
delayed growth and development, intellectual
disability, liver disease, and kidney problems.

18. NUTRITION THERAPY

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