CHEDIAK HIGASHI CHEDIAK HIGASHI SYNDROMESYNDROME

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 from amicrotubule polymerization defect which leads to a decrease in phagocytosis. which leads to a decrease in phagocytosis. The decrease in phagocytosis results in The decrease in phagocytosis results in recurrent pyogenic infections, partial recurrent pyogenic infections, partial albinism and peripheral neuropathyalbinism and 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

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

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

CHRISTIAN LEE

ACCELERATED PHASEACCELERATED PHASE

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

DiagnosisDiagnosis

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

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

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 patients. Infections are treated with antibiotics and abscesses are surgically antibiotics and abscesses are surgically drained when appropriate. Antiviral drugs drained when appropriate. Antiviral drugs such as acyclovir have been tried during the such as acyclovir have been tried during the terminal phase of the disease. terminal phase of the disease. Cyclophosphamide and prednisone have been Cyclophosphamide and prednisone have been tried. Vitamin C therapy has improved tried. Vitamin C therapy has improved immune function and clotting in some patients immune function and clotting in some patients

PHENYLKETENURIAPHENYLKETENURIA

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

SIGNS AND SYMPTOMSSIGNS AND SYMPTOMS

Infants with classic PKU appear normal until they Infants with classic PKU appear normal until they are a few months old.are a few months old.

Without treatment with a special low-Without treatment with a special low-phenylalanine diet, these children develop phenylalanine diet, these children develop permanent intellectual disability.permanent intellectual disability.

Seizures, delayed development, behavioral Seizures, delayed development, behavioral problems, and psychiatric disorders.problems, and psychiatric disorders.

Untreated individuals may have a musty or Untreated individuals may have a musty or mouse-like odor as a side effect of excess mouse-like odor as a side effect of excess phenylalanine in the body.phenylalanine in the body.

Children with classic PKU tend to have lighter skin Children with classic PKU tend to have lighter skin and hair than unaffected family members and are and hair than unaffected family members and are also likely to have skin disorders such as eczemaalso likely to have skin disorders such as eczema..

Less severe forms of this condition, Less severe forms of this condition, sometimes called variant PKU and non-sometimes called variant PKU and non-PKU hyperphenylalaninemia, have a smaller PKU hyperphenylalaninemia, have a smaller risk of brain damage. People with very mild risk of brain damage. People with very mild cases may not require treatment with a low-cases may not require treatment with a low-phenylalanine diet.phenylalanine diet.

These infants may also have a low birth These infants may also have a low birth weight and grow more slowly than other weight and grow more slowly than other children.children.

Other characteristic medical problems Other characteristic medical problems include heart defects or other heart include heart defects or other heart problems, an abnormally small head size problems, an abnormally small head size (microcephaly), and behavioral problems.(microcephaly), and behavioral problems.

Women with PKU and uncontrolled Women with PKU and uncontrolled phenylalanine levels also have an increased phenylalanine levels also have an increased risk of pregnancy lossrisk of pregnancy loss..

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

DIAGNOSISDIAGNOSIS

PKU can be easily detected with a simple PKU can be easily detected with a simple blood test. All states in the US require a PKU blood 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 newborn screening panel. The test is generally done by taking a few drops of generally done by taking a few drops of blood from the baby before the baby leaves blood from the baby before the baby leaves the hospital.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 blood and urine tests are required to confirm the diagnosis.the diagnosis.

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. phenylalanine, particularly when the child is growing. The diet must be strictly followed. This requires close The 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 cooperation of the parent and child. Those who continue the diet into adulthood have better physical continue the diet into adulthood have better physical and mental health. “Diet for life” has become the and mental health. “Diet for life” has become the standard recommended by most experts. This is standard recommended by most experts. This is especially important before conception and especially important before conception and throughout pregnancy.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 protein source that is extremely low in phenylalanine and balanced for the remaining essential amino acids and balanced for the remaining essential amino acids

DENTINOGENESIS DENTINOGENESIS IMPERFECTA IMPERFECTA

Dentinogenesis imperfectaDentinogenesis imperfecta (hereditary  (hereditary Opalescent Dentin) is a genetic Opalescent Dentin) is a genetic disorder of tooth development.disorder of tooth development.

causes teeth to be discolored (most often causes teeth to be discolored (most often a blue-gray or yellow-brown color) and a blue-gray or yellow-brown color) and translucent.translucent.

Teeth are also weaker than normal, Teeth are also weaker than normal, making them prone to rapid wear, making them prone to rapid wear, breakage, and loss. These problems can breakage, and loss. These problems can affect both primary (baby) teeth and affect both primary (baby) teeth and permanent teeth. permanent teeth.

This condition is inherited in an autosomal This condition is inherited in an autosomal dominant pattern, which means one copy dominant pattern, which means one copy of the altered gene in each cell is sufficient of the altered gene in each cell is sufficient to cause the disorder. to cause the disorder. 

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 imperfecta is of recessive type recessive 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

TYPE IITYPE II

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

CLINICAL FEATURESCLINICAL FEATURES

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

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 Type III shows thin dentin and extremely enormous pulp extremely enormous pulp chamber.These teeth are usually known chamber.These teeth are usually known as Shell Teethas 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 matrix are seen. Sometimes odontoblasts are seen in odontoblasts are seen in dentindentin..

TREATMENTTREATMENT

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