CARBOHYDRATE
METABOLISM- INHERITED
DISORDERS
DR. Tagreed Osman
•
Carbohydrates are sugars. Some
sugars are simple, and others are
more complex. Sucrose (table sugar)
is made of two simpler sugars called
glucose and fructose. Lactose (milk
sugar) is made of glucose and
galactose. Both sucrose and lactose
must be broken down into their
component sugars by enzymes before
the body can absorb and make use of
them.
 The
carbohydrates in bread, pasta,
rice, and other carbohydratecontaining foods are long chains of
simple sugar molecules. These
longer molecules must also be
broken down by the body.
 If an enzyme needed to process a
certain sugar is missing, the sugar
can accumulate in the body, causing
problems
1- GLYCOGEN STORAGE DISEASES
 Glycogen
is a glucose polymer joined in
straight chains. It can have a molecular
weight of many millions.
 Glycogen is the storage form of glucose
and is found in abundance in the liver,
muscles and kidneys.
 liver: stored for replenishing blood glucose
during food deprivation or stress (up to
6%)
 muscle:
stored for providing fuel during high
intensity exercise in the cell where stored
 Glycogen phosphorylase, the first enzyme in
glycogen breakdown, has a
different form
in liver and muscle
 Glycogen storage diseases are a group of
inherited disorders caused by a
 defect in glycogen metabolism characterized
by impaired conversion of glycogen to free
glucose resulting in the accumulation of
normal and abnormal glycogen in tissues,
leading to muscular weakness or even death.
There are many different glycogen storage
diseases (also called glycogenoses), each
identified by a roman numeral.
 These diseases are caused by a hereditary
lack of one of the enzymes that is essential to
the process of forming glucose into glycogen
and breaking down glycogen into glucose.
About 1 in 20,000 infants has some form of
glycogen storage disease.
 Some of these diseases cause few symptoms;
others are fatal.

Glycogen storage diseases tend to cause
uric acid, a waste product, to accumulate
in the joints (which can cause gout) and in
the kidneys (which can cause kidney
stones).
 The specific diagnosis is made when a
chemical examination of a sample of
tissue, usually muscle or liver, determines
that a specific enzyme is missing.
 Treatment depends on the type of
glycogen storage disease.

2- GALACTOSEMIA
Galactose is a sugar that is found in many
foods. When lactose is broken down in the
body, glucose and galactose are produced.
 Galactose is converted into glucose in the
body for energy.
 Galactosemia (a high blood level of
galactose) is caused by lack of one of the
enzymes necessary for metabolizing
galactose, a sugar present in lactose (milk
sugar). A metabolite builds up that is toxic
to the liver and kidneys and also damages
the lens of the eye, causing cataracts.

A newborn with galactosemia seems normal at
first but within a few days or weeks loses his
appetite, vomits, becomes jaundiced, has
diarrhea, and stops growing normally. White
blood cell function is affected, and serious
infections can develop. If treatment is delayed,
affected children remain short and become
mentally retarded or may die.
 Galactosemia is detectable with a blood test.
This test is performed as a routine screening
test on newborns in nearly all states in the
United States and particularly in those with a
family member known to have the disorder.

Galactosemia is treated by completely
eliminating milk and milk products—the
source of galactose—from an affected
child's diet.
 Galactose is also present in some fruits,
vegetables, and sea products, such as
seaweed.
 Doctors are not sure whether the small
amounts in these foods cause problems in
the long term.

 People
who have the disorder must restrict
galactose intake throughout life. If
galactosemia is recognized at birth and
adequately treated, the liver and kidney
problems do not develop, and initial mental
development is normal.
 However, even with proper treatment, children
with galactosemia often have a lower
intelligence quotient (IQ) than their siblings,
and they often have speech problems.
 Girls often have ovaries that do not function,
and only a few are able to conceive naturally.
Boys, however, have normal testicular
function.
SIGNS AND SYMPTOMS

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

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At birth: Jaundice after
milk consumption
Aminoaciduria: High
levels of amino acids in
urine and/or plasma
Hepatomegaly
Hypoglycemia
Ascites - fluid
accumulation in the
abdomen
High Galactose
concentrations in urine
COMPLICATIONS
 Renal
Dysfunction
 Premature
Ovarian Failure
 Poor growth and
balance
 Delayed speech
development
 Mental retardation
 Vomiting
 Hepatomegaly
 Lethargy
 Diarrhea
 Increased
susceptibility to
bacterial infections
 Hemolytic anemia
 Cataracts
 Death
3- HEREDITARY FRUCTOSE INTOLERANCE
 It
is a rare autosomal recessive disorder of
fructose metabolism.
 In this disorder, the body is missing an enzyme
(fructose-1-phosphate aldolase) that allows it to
use fructose, a sugar present in table sugar
(sucrose) and many fruits. As a result, a byproduct of fructose accumulates in the body,
blocking the formation of glycogen and its
conversion to glucose for use as energy. Ingesting
more than tiny amounts of fructose or sucrose
causes low blood sugar levels (hypoglycemia),
with sweating, confusion, and sometimes
seizures and coma.
 Children
who continue to eat foods
containing fructose develop kidney and liver
damage, resulting in jaundice, vomiting,
mental deterioration, seizures, and death.
Chronic symptoms include poor eating,
failure to thrive, digestive symptoms, liver
failure, and kidney damage.
 The diagnosis is made by: DNA Testing
which is A rapid, non-invasive test that
requires only a small blood sample, Liver
Biopsy Testing for assaying of aldolase,
Fructose Tolerant Testing and Hydrogen
Breath Test
 Treatment
involves excluding
fructose (generally found in
sweet fruits), sucrose, and
sorbitol (a sugar substitute)
from the diet.
 Acute attacks respond to
glucose given intravenously;
milder attacks of hypoglycemia
are treated with glucose tablets,
which should be carried by
anyone who has hereditary
fructose intolerance.