Chediak higashi syndrome, Phenylketonuria, Dentinogenesis Imperfecta

1. CHEDIAK HIGASHI CHEDIAK HIGASHI
SYNDROMESYNDROME

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

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

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

5. CHRISTIAN
LEE

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

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

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

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

11. PHENYLKETENURIAPHENYLKETENURIA

12. 
Phenylketonuria (commonly known as PKU) is Phenylketonuria (commonly known as PKU) is
an inherited disorder that increases the levels of an inherited disorder that increases the levels of
a substance called phenylalanine in the blood. a substance called phenylalanine in the blood.
Phenylalanine is a building block Phenylalanine is a building block
of proteins (an amino acid) that is obtained of proteins (an amino acid) that is obtained
through the diet. It is found in all proteins and in through the diet. It is found in all proteins and in
some artificial sweeteners. If PKU is not treated, some artificial sweeteners. If PKU is not treated,
phenylalanine can build up to harmful levels in phenylalanine can build up to harmful levels in
the body, causing intellectual disability and other the body, causing intellectual disability and other
serious health problems.serious health problems.

13. SIGNS AND SYMPTOMSSIGNS AND SYMPTOMS

Infants with classic PKU appear normal until they are a Infants with classic PKU appear normal until they are a
few months old.few months old.

Without treatment with a special low-phenylalanine diet, Without treatment with a special low-phenylalanine diet,
these children develop permanent intellectual disability.these children develop permanent intellectual disability.

Seizures, delayed development, behavioral problems, Seizures, delayed development, behavioral problems,
and psychiatric disorders.and psychiatric disorders.

Untreated individuals may have a musty or mouse-like Untreated individuals may have a musty or mouse-like
odor as a side effect of excess phenylalanine in the odor as a side effect of excess phenylalanine in the
body.body.

Children with classic PKU tend to have lighter skin and Children with classic PKU tend to have lighter skin and
hair than unaffected family members and are also likely hair than unaffected family members and are also likely
to have skin disorders such as eczemato have skin disorders such as eczema..

14. 
Less severe forms of this condition, sometimes Less severe forms of this condition, sometimes
called variant PKU and non-called variant PKU and non-
PKU hyperphenylalaninemia, have a smaller risk PKU hyperphenylalaninemia, have a smaller risk
of brain damage. People with very mild cases of brain damage. People with very mild cases
may not require treatment with a low-may not require treatment with a low-
phenylalanine diet.phenylalanine diet.

These infants may also have a low birth weight These infants may also have a low birth weight
and grow more slowly than other children.and grow more slowly than other children.

Other characteristic medical problems include Other characteristic medical problems include
heart defects or other heart problems, an heart defects or other heart problems, an
abnormally small head size (microcephaly), and abnormally small head size (microcephaly), and
behavioral problems.behavioral problems.

Women with PKU and uncontrolled Women with PKU and uncontrolled
phenylalanine levels also have an increased risk phenylalanine levels also have an increased risk
of pregnancy lossof pregnancy loss..

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

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

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

18. DENTINOGENESIS DENTINOGENESIS
IMPERFECTA IMPERFECTA

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

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

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

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

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

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