1. CHEDIAK HIGASHI
SYNDROME

2.  Chédiak–Higashi syndrome is a
rare autosomal recessive disorder that arises
from amicrotubule polymerization defect which
leads to a decrease in phagocytosis. The
decrease in phagocytosis results in
recurrent pyogenic infections, partial albinism
and peripheral neuropathy
 Mutations have been found in the CHS1 (also
called LYST) gene. The primary defect in this
disease is in special granules present in skin
pigment cells and certain white blood cells

3.  Chédiak–Higashi syndrome is caused by
mutations in the LYST gene. This gene
provides instructions for making a protein
known as the lysosomal trafficking
regulator

4. SIGNS AND SYMPTOMS
 Light skin
 Silvery hair
 Frequently complain of solar sensitivity
 Photophobia
 Infections involve mucous membranes,
skin, and respiratory tract.
 Neuropathy are common

5. CHRISTIAN
LEE

6. ACCELERATED PHASE
 Most children with Chédiak–Higashi syndrome ultimately
reach a stage known as the accelerated phase — the
lymphoma-like-syndrome. This severe phase of the
disease is thought to be triggered by a viral infection
(usually the Epstein–Barr virus, EBV). In the accelerated
phase, defective white blood cells divide uncontrollably
and invade many of the body's organs. The accelerated
phase is associated with fever, episodes of abnormal
bleeding, overwhelming infections, and organ failure.
These medical problems are usually life-threatening in
childhood.

7. Diagnosis
 The diagnosis is confirmed by bone
marrow smears that show "giant inclusion
bodies" in the cells that develop into white
blood cells (leukocyte precursor cells).
CHS can be diagnosed prenatally by
examining a sample of hair from a fetal
scalp biopsy or testing leukocytes from a
fetal blood sample

8.  Under light microscopy the hairs present
evenly distributed, regular melanin
granules, larger than those found in
normal hairs. Under polarized light
microscopy these hairs exhibit a bright
and polychromatic refringence pattern

10. TREATMENT
 There is no specific treatment for Chédiak–
Higashi syndrome. Bone marrow transplants
appear to have been successful in several
patients. Infections are treated with antibiotics
and abscesses are surgically drained when
appropriate. Antiviral drugs such as acyclovir
have been tried during the terminal phase of the
disease. Cyclophosphamide and prednisone
have been tried. Vitamin C therapy has
improved immune function and clotting in some
patients

11. PHENYLKETENURIA

12.  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.

13. SIGNS AND SYMPTOMS
 Infants with classic PKU appear normal until they are a
few months old.
 Without treatment with a special low-phenylalanine diet,
these children develop permanent intellectual disability.
 Seizures, delayed development, behavioral problems,
and psychiatric disorders.
 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.

14.  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.
 These infants may also have a low birth weight
and grow more slowly than other children.
 Other characteristic medical problems include
heart defects or other heart problems, an
abnormally small head size (microcephaly), and
behavioral problems.
 Women with PKU and uncontrolled
phenylalanine levels also have an increased risk
of pregnancy loss.

15. (A), trace diffusion-weighted
(B), and ADCav
(C) images show extensive white matter abnormalities with restricted diffusion.

16. DIAGNOSIS
 PKU can be easily detected with a simple blood
test. All states in the US require a PKU
screening test for all newborns as part of the
newborn screening panel. The test is generally
done by taking a few drops of blood from the
baby before the baby leaves the hospital.
 If the initial screening test is positive, further
blood and urine tests are required to confirm the
diagnosis.

17. TREATMENT
 Treatment involves a diet that is extremely low in
phenylalanine, particularly when the child is growing. The
diet must be strictly followed. This requires close
supervision by a registered dietitian or doctor, and
cooperation of the parent and child. Those who continue
the diet into adulthood have better physical and mental
health. “Diet for life” has become the standard
recommended by most experts. This is especially
important before conception and throughout pregnancy.
 A special infant formula called Lofenalac is made for
infants with PKU. It can be used throughout life as a
protein source that is extremely low in phenylalanine and
balanced for the remaining essential amino acids

18. DENTINOGENESIS
IMPERFECTA

19.  Dentinogenesis imperfecta (hereditary
Opalescent Dentin) is a genetic disorder of tooth
development.
 causes teeth to be discolored (most often a blue-
gray or yellow-brown color) and translucent.
 Teeth are also weaker than normal, making
them prone to rapid wear, breakage, and loss.
These problems can affect both primary (baby)
teeth and permanent teeth.
 This condition is inherited in an autosomal
dominant pattern, which means one copy of the
altered gene in each cell is sufficient to cause
the disorder.

20. TYPES
 TYPE I
- usually an autosomal
dominant trait with
variable expressivity but
can be recessive if the
associated osteogenesis
imperfecta is of recessive
type
- usually involved and
more severely affected
are deciduous teeth in
type 1

21.  TYPE II
- Occurs in people without
other inherited disorders
(i.e. Osteogenesis
imperfecta).It is an
autosomal dominant trait.
A few families with type II
have progressive hearing
loss in addition to dental
abnormalities.

22. CLINICAL FEATURES
 The teeth may be gray to yellowish brown.
They exhibit translucent or opalescent
hue. Enamel is usually lost early due to
loss of scalloping at the DEJ. However,
the teeth are not more susceptible
to dental caries than normal ones.

23. RADIOGRAPGIC
APPEARANCE
 Type I and II show total obliteration of
the pulp chamber.
 Type III shows thin dentin and extremely
enormous pulp chamber.These teeth are
usually known as Shell Teeth .
 Histology
 Dentinal tubules are irregular and are
bigger in diameter. Areas of uncalcified
matrix are seen. Sometimes odontoblasts
are seen in dentin .

25. TREATMENT
 One treatment option is bonding, putting lighter enamel
on the weakened enamel of the teeth and with lots of
treatments of this bonding, the teeth appear whiter to the
eye, but the teeth on the inside and under that cover are
still the same. Due to the weakened condition of the
teeth, many common cosmetic procedures such as
braces and bridges are inappropriate for patients with
Dentinogenesis imperfecta and are likely to cause even
more damage than the situation they were intended to
correct.