Mendelian Disorders
Mendelian Disorders
Mendelian Disorders
AKU GENE
Located on Chromosome 3(q2)
metabolised
Homogentisate
1,2 dioxygenase
DIETARY PROTEIN
100g of protein = 4g of Phenylalanine/3g of Tyrosine
MALEYLACETOACETATE
TYROSINE
Homogentisic acid 1,2 dioxygenase (HGD) deficiency
BLOCK IN ALKAPTONURIA
2 (0)
POLYMER
(0)
HOMOGENTISIC ACID HGA
BENZOQUINONE HGA (Ochronotic
POLYPHENOL ACETIC ACID POLYPHENOL Pigment)
OXIDASE OXIDASE
(CU++) (CU++)
HO OH o= =o o= =o
CH2COOH CH2COOH
CH2COOH
n
PHYSICAL
BONDING CHEMICAL
BONDING
body cells
mucous secretions
synovial fluids
Genetic disorders
Excessive accumulation of
mucopolysaccharides in body tissues
• Results:
– many serious physical disorders
– Various genetic deformities such as:
• skeletal deformities (especially of the face)
• mental retardation
• decreased life expectancy
Examples
• Hunter syndrome
• Hurler syndrome
• Scheie syndrome
• Sanfilippo syndrome
• Morquio disease
• Maroteaux-Lamy syndrome
Hurler syndrome (type
I)
Hurler syndrome type I
Mucopolysaccharidosis I (MPS I) Disease
)Hurler, Hurler-Scheie, Scheie Syndromes(
Hernia Corneal Coarse Claw hand
clouding facial
features
Causes of the Hurler syndrome
* characteristics –
galactosemia affects
the body’s ability to
process galactose (a
sugar found in dairy
products)
Galactosaemia
• Reason: Deficiency of galactose-1-p-uridyl transferase ,
which is essential for galactose metabolism.
• A rare recessive trait
• Galactose-1-phosphate uridyltransferase deficiency,
• Accumulation of galactose in the blood
• Increasing the risk of mental retardation
• Incidence:
– 1/50.000-1/100.000
• Genetic locus: 9p13
• Screening test:
– Lactose-free diet (Soy formula, galactose restricition)
Mode of Inheritance
* galactosemia –
autosomal recessive
(a child has to inherit
one gene from each
parent that is defective)
* galactosemia is on
chromosome 9
Punnett Square
PKU (phenylketonuria),
in its "classic" form, is a
rare, inherited metabolic
disease that results in
mental retardation and
other neurological
problems when
treatment is not started
within the first few
weeks of life. .
PHENYLALANINE
PKU is characterized
by the inability of the
body to utilize the
essential amino acid
phenylalanine.
WHATS THE DIFFERENCE
BETWEEN ESSENTIAL AND NON-
ESSENTIAL AMINO ACIDS?
Amino acids are the
building blocks for
body proteins.
Essential amino acids can
only be obtained from
the food we eat as our
body does not normally
produce them.
ENZYMATIC ACTIVITY
• In cases of PKU, the enzyme that breaks down
phenylalanine, phenylalanine hydroxylase, is completely
or nearly completely deficient.
PKU is inherited as
an autosomal
recessive trait.
• Two people who
conceive a child must
both be the carriers of
the defective gene in
order for their child to
have the disorder.
Vomitting
Irritability
Eczema-like rash
Unusual odor to urine
Nervous System Problems(increased muscle tone,
more active muscle tendon reflexes)
Microcephaly
Decreased body growth
OTHER SYMPTOMS OF PKU
• Prominent cheek and jaw bones widely
spaced teeth
• NutraSweet in particular,
should be avoided
because it is a derivative
of phenylalanine.
HELPFUL WEBSITES FOR LOW
PROTEIN FOODS
*http://
www.cambrookefoods
.com/
http://
www.waisman.wisc.ed
u/foods/
lowprotein.html
LIFESTYLE ADJUSTMENTS FOR
PKU PATIENTS
• More frequent doctor visits
• Required dietary restrictions that may
impact day to day activities.
• Permanent monitoring of blood
phenylalanine levels
Sex-linked genes in humans
Pigmented iris
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