Makalah Bahasa Inggris 3,1correlation between thallasemia and the development of jaw and teeth

The Correlation Between Thalassemia and The Development Of Jaw and Teeth

Abstract

Thalassemia beta major is a hereditary hemolytic anemia disease with various grades

of severity, which can be found with no or less globin chain qualitative synthesis. The patient

often experiences hepatosplenomegaly, growth retardation and bone disorder and the

thalassemia facies/chipmunk face protrusive premaxillae due to erythroid hyperplasia with

depressed bridge of the nose. The dentition shows protrusion, flaring and spacing of the

maxillary anterior teeth, open bite that leads to malocclusion. The oral cavity of the beta

major thalassemia patients shows the following characteristics the upper jaw seems to be

bigger due to the bone marrow expansion.The thalassemias were first discovered by Thomas

Cooley and Pearl Lee in 1975. Early cases of the disease were reported in children of

Mediterranean descent and therefore the disease was named after the Greek word for

sea, thalasa. Thalassemia faces is one of the important symptoms of this disease. This kind of

symptoms may occur at birth or the first two years of life.

Keyword : Thalassemia Beta Major, Thalassemia faces, Dental development disorder

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http://www.healthline.com/adamcontent/acute-mountain-sickness

http://www.healthline.com/adamcontent/thalassemia


CHAPTER I

Introduction

Thalassemia is an inherited disorder of hemoglobin (Hb) synthesis, so it is an anemia

transmits congenitally. Thalassemia varies from asymptomatic forms to severe or even fatal

entities. Thalassemia has names as “Mediterranean anemia”, (Whipple et al) Cooley anemia

“Thomas Cooley”, or β thalassemia. The malocclusion “Thalassemia caused” is available to

be prevented by “intensive blood transfusion programme or by bone-marrow-

transplantation”. However, such preventive procedures should be followed for the growing

children since the first years of their lives. Unfortunately, the substitution of preventive

treatments (since the childhood first years) is the surgery with its sequels and aftermaths.

It has been reported in the literature that the major oral change in thalassaemic patients is

enlargement of the maxilla caused by bone marrow expansion. This results in a characteristic

appearance known as chipmunk faces. Affected patients usually suffer from spacing of the

teeth and forward drift of the maxillary incisors, so that orthodontic treatment may be

indicate.

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CHAPTER II

THALASSEMIA

Beta-thalassemia syndromes are a group of hereditary blood disorders characterized by

reduced or absent beta globin chain synthesis, resulting in reduced Hb in red blood cells

(RBC), decreased RBC production and anemia. Most thalassemias are inherited as recessive

traits. Beta-thalassemias can be classified into:

- Beta-thalassemia

• Thalassemia major

•Thalassemia intermedia

•Thalassemia minor

- Beta-thalassemia with associated Hb anomalies

• HbC/Beta-thalassemia

• HbE/Beta-thalassemia

• HbS/Beta-thalassemia (clinical condition more similar to sickle cell disease than to

thalassemia major or intermedia)

- Hereditary persistence of fetal Hb and beta-thalassemia

- Autosomal dominant forms

- Beta-thalassemia associated with other manifestations

• Beta-thalassemia-tricothiodystrophy

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• X-linked thrombocytopenia with thalassemia

Clinical presentation of thalassemia major occurs between 6 and 24 months. Affected infants

fail to thrive and become progressively pale. Feeding problems, diarrhea, irritability,

recurrent bouts of fever, and progressive enlargement of the abdomen caused by spleen and

liver enlargement may occur. In some developing countries, where due to the lack of

resources patients are untreated or poorly transfused, the clinical picture of thalassemia major

is characterized by growth retardation, pallor, jaundice, poor musculature, genu valgum,

hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis,

and skeletal changes resulting from expansion of the bone marrow. Skeletal changes include

deformities in the long bones of the legs and typical craniofacial changes (bossing of the

skull, prominent malar eminence, depression of the bridge of the nose, tendency to a

mongoloid slant of the eye, and hypertrophy of the maxillae, which tends to expose the upper

teeth).

If a regular transfusion program that maintains a minimum Hb concentration of 9.5 to 10.5

g/dL is initiated, growth and development tends to be normal up to 10 to 12 years. Transfused

patients may develop complications related to iron overload. Complications of iron overload

in children include growth retardation and failure or delay of sexual maturation. Later iron

overload-related complications include involvement of the heart (dilated myocardiopathy or

rarely arrythmias), liver (fibrosis and cirrhosis), and endocrine glands (diabetes mellitus,

hypogonadism and insufficiency of the parathyroid, thyroid, pituitary, and, less commonly,

adrenal glands). Other complications are hypersplenism, chronic hepatitis (resulting from

infection with viruses that cause hepatitis B and/or C), HIV infection, venous thrombosis, and

osteoporosis. The risk for hepatocellular carcinoma is increased in patients with liver viral

infection and iron overload. Compliance with iron chelation therapy (see later) mainly

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influences frequency and severity of the iron overload-related complications. Individuals who

have not been regularly transfused usually die before the second-third decade. Survival of

individuals who have been regularly transfused and treated with appropriate chelation

extends beyond age of 40 years. Cardiac disease caused by myocardial siderosis is the most

important life-limiting complication of iron overload in beta-thalassemia. In fact, cardiac

complications are the cause of the deaths in 71% of the patients with beta-thalassemia major.

The etiology is more than 200 mutations have been so far reported; the large majority are

point mutations in functionally important regions of the beta globin gene. Deletions of the

beta globin gene are uncommon. The beta globin gene mutations cause a reduced or absent

production of beta globin chains.

The pathophysiology is the reduced amount (beta+) or absence (beta0) of beta globin chains

result in a relative excess of unbound alpha globin chains that precipitate in erythroid

precursors in the bone marrow, leading to their premature death and hence to ineffective

erythropoiesis. The degree of globin chain reduction is determined by the nature of the

mutation at the beta globin gene located on chromosome 11.

Peripheral hemolysis contributing to anemia is less prominent in thalassemia major than in

thalassemia intermedia, and occurs when insoluble alpha globin chains induce membrane

damage to the peripheral erythrocytes. Anemia stimulates the production of erythropoietin

with consequent intensive but ineffective expansion of the bone marrow (up 25 to 30 times

normal), which in turn causes the typical previously described bone deformities. Prolonged

and severe anemia and increased erythropoietic drive also result in hepatosplenomegaly and

extramedullary erythropoiesis.[1,2]

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Tests and diagnosis

Most children with moderate to severe thalassemia show signs and symptoms within their

first two years of life. If your doctor suspects your child has thalassemia, he or she may

confirm a diagnosis using blood tests.

If your child has thalassemia, blood tests may reveal:

A low level of red blood cells

Smaller than expected red blood cells

Pale red blood cells

Red blood cells that are varied in size and shape

Red blood cells with uneven hemoglobin distribution, which gives the cells a bull's-eye

appearance under the microscope

Blood tests may also be used to:

Measure the amount of iron in your child's blood

Evaluate his or her hemoglobin

Perform DNA analysis to diagnose thalassemia or to determine if a person is carrying

mutated hemoglobin genes

Prenatal testing

Testing can be done before a baby is born to find out if it has thalassemia and determine how

severe it may be. Tests used to diagnose thalassemia in fetuses include:

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Chorionic villus sampling. This test is usually done around the 11th week of pregnancy and

involves removing a tiny piece of the placenta for evaluation.

Amniocentesis. This test is usually done around the 16th week of pregnancy and involves

taking a sample of the fluid that surrounds the fetus.

Assisted reproductive technology. A form of assisted reproductive technology that

combines pre-implantation genetic diagnosis with in vitro fertilization may help parents who

have thalassemia or who are carriers of a defective hemoglobin gene give birth to healthy

babies. The procedure involves retrieving mature eggs from a woman and fertilizing them

with a man's sperm in a dish in a laboratory. The embryos are tested for the defective genes,

and only those without genetic defects are implanted in the woman.[3]

Treatments and drugs

Treatment for thalassemia depends on which type you have and how severe it is.

Treatments for mild thalassemia

Signs and symptoms are usually mild with thalassemia minor and little, if any, treatment is

needed. Occasionally, you may need a blood transfusion, particularly after surgery, after

having a baby or to help manage thalassemia complications.

Treatment for moderate to severe thalassemia

Treatments for moderate to severe thalassemia may include:

Frequent blood transfusions. More-severe forms of thalassemia often require frequent

blood transfusions, possibly every few weeks. Over time, blood transfusions cause a buildup

of iron in your blood, which can damage your heart, liver and other organs. To help your

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body get rid of the extra iron, you may need to take medications that rid your body of extra

iron.

Stem cell transplant. Also called a bone marrow transplant, a stem cell transplant may be

used to treat severe thalassemia in select cases. Prior to a stem cell transplant, you receive

very high doses of drugs or radiation to destroy your diseased bone marrow. Then you

receive infusions of stem cells from a compatible donor. However, because these procedures

have serious risks, including death, they're generally reserved for people with the most severe

disease who have a well-matched donor available — usually a sibling.[4]

Prognosis

Prognosis of thalassemia minor subjects is excellent. An increased risk for cholelithiasis,

especially in association with the Gilbert mutation has been demonstrated. Patients with

thalassemia intermedia who do not usually have severe hemosiderosis are less prone to

cardiac problems. However, pulmonary hypertension, thromboembolic complications,

overwhelming postsplenectomy sepsis, and the development of hepatocarcinoma may reduce

survival in this group of patients. The prognosis of betathalassemia major was very grim

before there was any treatment available. With no treatment, the natural history was for death

by age five from infections and cachexia. The first advance in treatment was the initiation of

episodic blood transfusions when the patient was having a particularly bad time. With the

advent of this type of therapy, survival was prolonged into the second decade, but it soon

became evident that the treatment that saved lives in children caused death from cardiac

disease in adolescence or early childhood. Prognosis for individuals with betathalassemia

major has dramatically improved with the advent of DFO. However, many transfusion-

dependent patients continued to develop progressive accumulation of iron. This can lead to

tissue damage and eventually death, particularly from cardiac disease. Advances in red cell

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transfusion, and the introduction of new iron chelators and chelation regimes have further

prolonged survival in recent years.

Assessment of myocardial siderosis and monitoring of cardiac function combined with

intensification of iron chelation have converted a once universally fatal disease to a chronic

illness and an excellent long-term prognosis is expected for children who have been chelated

since a very young age.

Bone marrow transplantation is at present the only available definitive cure for patients with

thalassemia major.[2]

CHAPTER III

TOOTH DEVELOPMENT

Tooth Development

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The oral structures begin to form during the third and fourth weeks of embryonic

development. Germ cells from the ectoderm, mesoderm, and endoderm all contribute to tooth

formation.

Tooth development is divided into the following stages: the bud, the cap, the bell, and crown

(maturation). Additional detail is beyond the scope of this effort and the necessary knowledge

base of practicing pediatricians.

However, it is important to know that the teeth begin to develop around the sixth week of

fetal life and that development continues throughout fetal life and beyond. Thus, an insult can

happen at any or multiple points in the development process and lead to abnormal outcomes.

For example, a febrile illness can cause enamThe order of eruption of the 20 primary and 32

permanent teeth is fairly predictable, although the timing can range considerably among

children.

Primary Teeth

The primary teeth begin to erupt around 6 months of age and eruption is completed by 24 to

36 months. Girls’ teeth usually erupt slightly earlier than boys. Delays in tooth eruption can

be familial, but delays of more than 12 months merit further dental evaluation.

Eruption is usually symmetrical (lower teeth usually before upper) in the following pattern

for the primary teeth: central incisors, lateral incisors, first molars, canines, second molars.

Exfoliation often follows a similar pattern. A helpful mnemonic to remember the timing of

primary eruption is the 7+4 rule. At 7 months of age, children should have their first teeth; at

11 months (4 months later), they should have 4 teeth. At 15 months of age

(4 months later), they should have 8 teeth, and so on. This pattern continues as follows:

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19 months = 12 teeth

23 months = 16 teeth

27 months =20 teeth

Permanent Teeth

Eruption is similar for the permanent teeth, beginning between 5 and 7 years and usually

finishing by 13 to 14 years. The typical pattern is: central incisors, lateral incisors, first

molars, premolars, canines, second molars, and third molars (wisdom teeth), although not

everyone develops or erupts third molars.

Natal and Neonatal Teeth

Some infants erupt teeth, usually lower incisors, before birth (natal teeth) or shortly thereafter

(neonatal teeth). This is relatively rare, with an incidence of 1 in 2000 children. Extraction of

these incisors may be considered if they are mobile, interfere with breastfeeding, or lead

to Riga-Fede ulceration.

Delayed tooth eruption of more than 12 months can be caused by the following medical

problems:

Endocrine disorders (eg, hypothyroidism, disorders of

calcium/phosphorus metabolism, hypopituitarism)

Genetic disorders (eg, ectodermal dysplasias, Down syndrome,

cleidocranial dysostosis)

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Oral space issues (eg, another tooth blocking eruption, impacted

teeth)

Dense gingival tissue (eg, anti-convulsant medications)

Dental Infection

Radiation therapy

Therefore, it is reasonable to refer a child who has not erupted a tooth by 18 months of age to

a dentist if they are not seeing one already.

Abnormal Teeth

A number of tooth abnormalities can occur in development. These can relate to the shape,

color, physical structure, or number of teeth.

Number of Teeth

Hypodontia can be caused by some of the same problems that cause delayed tooth eruption

(eg, Down syndrome, ectodermal dysplasias, chemotherapy, radiation therapy). The

prevalence of hypodontia is approximately 3% in the United States, excluding the absence of

the third molars (wisdom teeth), which occurs in approximately 20% of individuals.

Anodontia is extremely rare and most often associated with hypohydrotic ectodermal

dysplasia.

Hyperdontia prevalence ranges from 0.1% to 3.8% and can be associated with genetic

disorders such as cleidocranial dysostosis and Gardner’s syndrome.

(Familial Adenomatous Polyposis).

Tooth Shape

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Abnormal tooth shape can result from a variety of medical conditions. Some recognizable

names of these abnormal teeth and their causes include Hutchinson incisors (congenital

syphilis), mulberry teeth (congenital syphilis), and conical teeth (ectodermal dysplasias).

Malocclusion, or a misalignment of the teeth, can be a functional problem (eg, eating), an

aesthetic issue, or a hindrance to maintaining good oral hygiene. Examples of malocclusion

include

anterior open bite,

anterior crossbite, and

posterior crossbite. [5]

Signs and symptoms of malocclusion include abnormal alignment of teeth, abnormal

appearance of the face, difficulty or discomfort when biting or chewing, and bruxism.

Malocclusion is usually genetic or congenital in origin. Examples of genetic causes include

congenital absence of teeth, cleft lip or palate, skeletal disorders, and muscular problems.

Malocclusion can also result from environmental factors, such as prolonged thumb sucking,

pacifier use, or tongue thrusting.

Many malocclusions are not preventable, as they are genetic in nature. However, helping

families address pacifier and thumb sucking issues at an early age may prevent or minimize

this problem.

Patients with malocclusions should be referred to a dental professional. Physicians can also

encourage patients treated by dental professionals to use prescribed appliances consistently

and as directed by the dental professional.[6]

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CHAPTER IV

Correlation

The Correlation between Thalassemia and the development of jaw and teeth is that

Thalassemia patient will have bone abnormalities such as overgrowth of the maxilla and the

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mandible. Chipmunk faces or Cooley faces is one of the most common sign of Thalassemic

patient because of the protrusion of maxilla and mandible,also protrusion of incisor teeth.

Orthodontist treating of this condition need to be aware of the importance of good diagnosis,

investigations and treatment plan.

CHAPTER V

Conclusion

Thalassemia is a hereditary hemolytic anemia disease with various grades of severity, which

can be found with no or less globin chain qualitative synthesis. The patient often experiences

hepatosplenomegaly, growth retardation and bone disorder and the thalassemia

15


facies,protrusive premaxillae due to erythroid hyperplasia with depressed bridge of the nose.

The dentition shows protrusion, flaring and spacing of the maxillary anterior teeth, open bite

that leads to malocclusion. The oral cavity of the beta major thalassemia patients shows the

following characteristics the upper jaw seems to be bigger due to the bone marrow expansion

We can confirm Thalassemia with blood test,and pre natal test,so we will know the severity

of the patient. The treatment for the patient have a variation of severity, and for the treatment

is also different.The prognosis of thalassemia minor patient is excellent but for the

thalassemia major patient,the only definitive treatment is bone marrow transplantation,that

can make an excellent prognosis.

References

1. The Orthodontic Cyber Journal. Thalassemia Patient With Malocclusion.

Available at : http://orthocj.com/2006/06/case-report-thalassemia-patients-

with-malocclusion. Accessed December 26, 2012.

2. Orphanet Journal of Rare Diseases. Beta Thalassemia. Available at :

http://www.ojrd.com/content/5/1/11. Accessed December 26, 2012.

16

http://www.ojrd.com/content/5/1/11.%20Accessed%20December%2026

http://orthocj.com/2006/06/case-report-thalassemia-patients-with-malocclusion.%20Accessed%20December%2026

http://orthocj.com/2006/06/case-report-thalassemia-patients-with-malocclusion.%20Accessed%20December%2026


3. Thalassemia. Test and Diagnosis. Available at :

http://www.mayoclinic.com/health/thalassemia/DS00905/DSECTION=tests-

and-diagnosis. Accessed December 26, 2012

4. Thalassemia. Treatment and Drugs. Available at :

http://www.mayoclinic.com/health/thalassemia/DS00905/DSECTION=treatm

ents-and-drugs. Accessed December 26, 2012

5. American Academy of Pediatrics. Dental Development. Available at :

http://www2.aap.org/ORALHEALTH/pact/ch2_intro.cfm. Accessed

December 26, 2012

6. American Academy of Pediatrics. Maloclussion. Available at :

http://www2.aap.org/ORALHEALTH/pact/ch2_sect6.cfm. Accessed

December 26, 2012

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http://www2.aap.org/ORALHEALTH/pact/ch2_sect6.cfm.%20Accessed%20December%2026

http://www2.aap.org/ORALHEALTH/pact/ch2_sect6.cfm.%20Accessed%20December%2026

http://www2.aap.org/ORALHEALTH/pact/ch2_intro.cfm.%20Accessed%20December%2026

http://www2.aap.org/ORALHEALTH/pact/ch2_intro.cfm.%20Accessed%20December%2026

http://www.mayoclinic.com/health/thalassemia/DS00905/DSECTION=treatments-and-drugs

http://www.mayoclinic.com/health/thalassemia/DS00905/DSECTION=treatments-and-drugs

http://www.mayoclinic.com/health/thalassemia/DS00905/DSECTION=tests-and-diagnosis

http://www.mayoclinic.com/health/thalassemia/DS00905/DSECTION=tests-and-diagnosis

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Makalah Bahasa Inggris 3,1correlation between thallasemia and the development of jaw and teeth