Download 05. HEREDITARY METABOLIC DISEASES

HEREDITARY METABOLIC
DISEASES
Particular risk factors are:
•Advanced maternal age (e.g. Down's
syndrome)
• Family history of inherited diseases
(e.g. fragile X syndrome, Huntington's
chorea)
• Previous child with genetic disorder
(e.g. Tay-Sachs disease
PHENYLKETONURIA
 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
blood and is toxic to the brain, causing
mental retardation.
SYMPTOMS
mental retardation over the first few years
of life, which 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 urine odor as
a result of a by-product of
phenylalanine (phenylacetic acid)
in their urine and sweat.

MAPLE SYRUP URINE DISEASE
 By-products
of lecine, isoleucine
and valine build up, causing
neurologic changes, including
seizures and mental retardation.
These by-products also cause
body fluids, such as urine and
sweat, to smell like maple syrup

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 develop vomiting,
staggering, confusion, coma, and the odor
of maple syrup particularly during physical
stress, such as infection or surgery
 Infants
with severe disease are
treated with dialysis. Some children
with mild disease benefit from
injections of the vitamin B1 (thiamin).
After the disease has been brought
under control, children must always
consume a special artificial diet that is
low in the particular amino acids that
are affected by the missing enzyme.

HOMOCYSTINURIA

Children with homocystinuria are
unable to metabolize the amino acid
homocysteine, which, along with
certain toxic by-products
 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;
the child is usually tall and thin with a
curved spine, elongated limbs, and
long, spiderlike fingers.
 In
a few states, children are
screened for homocystinuria at
birth with a blood test. The
diagnosis is confirmed by a test
measuring enzyme function in
liver or skin cells.
TYROSINEMIA

There are two main types of tyrosinemia: I
and II. Type I tyrosinemia is most
common in 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 death.
 Type
II tyrosinemia is less common.
Affected children sometimes have
mental retardation and frequently
develop sores on the skin and eyes.
Unlike type I tyrosinemia, restriction
of tyrosine in the diet can prevent
problems from developing.
GLYCOGEN STORAGE
DISEASES

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.

GALACTOSEMIA
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.
Types and Characteristics of Glycogen Storage Diseases
Name
Affected Organs
Symptoms
Type O
Liver, muscle
Enlarged liver with accumulation of fat inside the liver cells
(fatty liver); episodes of low blood sugar levels (hypoglycemia)
when fasting
von Gierke's disease
(Type IA)
Liver, kidney
Enlarged liver and kidney; slowed growth; very low blood sugar
levels; abnormally high levels of acid, fats, and uric acid in blood
Type IB
Liver, white blood
cells
Same as in von Gierke's disease but may be less severe; low white
blood cell count; recurring mouth and intestinal infections or
Crohn's disease
Pompe's disease
(Type II)
All organs
Enlarged liver and heart, muscle weakness
Forbes' disease (Type
III)
Liver, muscle, heart,
white blood cells
Enlarged liver or cirrhosis; low blood sugar levels; muscle
damage and heart damage in some people
Andersen's disease
(Type IV)
Liver, muscle, most
tissues
Cirrhosis in juvenile type; muscle damage and heart failure in
adult (late-onset) type
McArdle's disease
(Type V)
Muscle
Muscle cramps or weakness during physical activity
Hers' disease (Type
VI)
Liver
Enlarged liver; episodes of low blood sugar when fasting; often
no symptoms
Tarui's disease (Type
VII)
Skeletal muscle, red
blood cells
Muscle cramps during physical activity; red blood cell
destruction (hemolysis)
 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.