Case: Below is the X-ray image of your patient. He is

small for his age, found to be anemic with

hepatospelenomegaly on your exam.

What is your diagnosis?

ANSWER:Beta-thalassemia

Introduction:

•Thalassemia is a hereditary disorder that results in a

defect in hemoglobin synthesis. This defect may

involve either the a α - or β -globulin genes.

•The resultant red blood cells have reduced

hemoglobin content and quantity, are thin, and have a

shortened life span.

•Beta-thalassemias characterized by anomalies in the

synthesis of the beta chains of hemoglobin resulting in

variabale phenotypes ranging from severe anemia to

clinically asymptomatic individuals.

Beta-thalassemia includes three

main forms:

•Thalassemia Major, variably referred to as"Cooley's

Anemia" and "Mediterranean Anemia“

•Thalassemia Intermedia

•and Thalassemia Minor also called "beta-thalassemia

carrier", "beta-thalassemia trait" or "heterozygous beta-

thalassemia"

•subjects with thalassemia major are homozygotes

•subjects with thalassemia intermedia are mostly

homozygotes or compound heterozygotes

•and subjects with thalassemia minor are mostly

heterozygotes.

molecular basis:

•Mutations in the HBB gene cause

beta thalassemia. More than 200

mutations have been so far reported.

•The HBB gene provides instructions

for making a protein called beta-

globin.

•Beta-globin is a component (subunit) of hemoglobin.

•Hemoglobin consists of four protein subunits, typically two

subunits of beta-globin and two subunits of another

protein called alpha-globin.

•Some mutations in the HBB gene prevent the

production of any beta-globin.

•The absence of beta-globin is referred to as beta-zero

(B0) thalassemia.

•Other HBB gene mutations allow some beta-globin to

be produced but in reduced amounts. A reduced

amount of beta-globin is called beta-plus (B+)

thalassemia.

•Having either B0 or B+ thalassemia

does not necessarily predict disease

severity, however; people with both

types have been diagnosed with

thalassemia major and thalassemia

intermedia.

•A lack of beta-globin leads to a reduced amount of

functional hemoglobin. Without sufficient hemoglobin,

red blood cells do not develop normally, causing a

shortage of mature red blood cells.

•The low number of mature red blood cells leads to

anemia and other associated health problems in people

with beta thalassemia.

Genetis basis:

(based on a 13-year experience in Iran)

•The most frequent beta-globin gene mutations were

IVS II-1 (G>A) (56.6%)The polymorphism at -153 of γG

with +/+alleles (55.2%) was the most common

presentation in this series

•Int J Hematol (2012) 95:51–56

Epidemiology

•Thalassemia is the most common single gene disorder

worldwide.

•The prevalence of thalassemia is very high in Iran

(1/66%) and about 3.5 million people in the country (5

percent of the population) are carriers of the disease.

•Previously about 1,800_2,000 children were born with

thalassemia every year but now the figure has reached

250-300.

Clinical Features of the face

•In the severe form of the disease, the onset is in

infancy and the survival time may be short. The face

develops prominent cheekbones and a protrusive

premaxilla, resulting in a “ rodentlike ” face.

•The milder form of the disease occurs in adults.

Chipmunk (or Rodent Face) Characterization of

Thalassemia

Chipmunk (or Rodent Face)

Characterization of Thalassemia

Normal view In thalassemia

Skull Radiographic Characteristics

of Thalassemia Patients

Etiology:

•Cooley’s original description of ß-

thalassaemia major included marked bone deformities

as a characteristic feature.

•These were thought to be due to expansion of

haemopoiesis attempting to compensate for the

congenital anaemia.

•Bone disease is an important cause of morbidity in

older patients with ß-thalassaemia major and

intermedia.

•reduced BMD of the spine, femoral neck and distal

radius was present in over two-thirds of adult patients

with ß-thalassaemia major and intermedia.

•Bone mass is known to be under strong genetic

control,but the genes involved are not yet well defined.

A candidate gene is the vitamin D receptor gene as

vitamin D plays a major role in bone mineralization and

calcium homeostasis.The relationship between the

BsmI VDR gene polymorphism and BMD is

controversial.

•thalassaemic patients with the BB genotype,previously

reported by some investigators to be associated with

decreased BMD, had significantly lower spine BMD than

those with the bb genotype, suggesting that the BsmI

VDR polymorphism may contribute to the severity of

osteopenia in thalassaemia.

•1-Severe bone marrow hyperplasia

prevents pneumatization of the

paranasal sinuses, especially the

maxillary sinus

Normal view

In thalassemia

2-Large bone marrow spaces were mainly

seen in the posterior mandibular region

Normal view In thalassemia

`

Normal view In thalassemia

3-Panoramic radiograph demonstrating absence

of both superior and inferior borders of the inferior

alveolar canal

4-thinning of the cortical borders`

Normal view In thalassemia

Dental signs•Spiky and short roots

•Taurodontism

•Thin lamina dura

Panoramic radiograph demonstrating

mandibular molars with thin, spiky roots

Normal view In thalassemia

Panoramic radiograph demonstrating

taurodontism of the maxillary molars

Normal view In thalassemia

Panoramic radiograph demonstrating

areas of thin lamina dura

Normal view In thalassemia