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Haemophilia
Haemophilia
is group of sex linked recessive disorders that impair the body's ability to
control blood clotting or coagulation, which is used to stop bleeding when a
blood vessel is broken. Haemophilia A (clotting factor VIII deficiency;
MIM: 306700)
is the most common form of the disorder, occurring at about 1 in 5,000 to
10,000 male births. Haemophilia B (factor IX deficiency;
MIM: 306900)
occurs at about 1 in about 20,000-34,000 male births,
with no significant racial difference. They
are clinically almost identical and are associated with spontaneous bleeding
into joints and muscles and internal or external bleeding after injury or
surgery. Both the conditions are X-linked and virtually all sufferers of
hemophilia are males. Female carriers may also bleed abnormally, because some
have low levels of the relevant clotting factor. Other deficiencies
of coagulation factors that cause a bleeding disorder, such as
afibrinogenaemia, hypoprothrombinaemia, deficiencies of factor V, combined
factor V and factor VIII, factor VII, factor X, factor XI, and factor XIII, are
inherited as autosomal recessive traits and are generally much rarer than the
hemophilias, with prevalence in the general population varying between
1:500,000 and 1:2,000,000. Apart from these, one of the most common heridetary
coagulation disorder is known as Von Willebrand disease, is inherited as
autosomanl dominant pattern. The birth rate haemophilia in India is 32 per
1,000 births.
Thalassemia
Thalassemia
is
a
blood related disorder that is mostly
transmitted in autosomal recessive mode.
In thalassemia, the genetic defect results in reduced rate of synthesis of one
of the globin chains that make up hemoglobin leading to the formation of
abnormal hemoglobin molecules, thus causing anemia, the characteristic
presenting symptom of the thalassemias. The disease is particularly prevalent
among Mediterranean people (especially among the Greeks). The
thalassemias are classified according to which chain of the
hemoglobin molecule is affected. In alpha thalassemias (
MIM: 141750
and
MIM: 301040),
production of alpha globin chain is affected, while in Beta thalassemia (
MIM: 603902)
production of beta globin chain is affected. alpha thalassemias
primarily involve the genes HBA1 and HBA2, beta thalassemias are due to
mutations in the HBB gene. It involves decreased production of normal adult
hemoglobin, the predominant type of hemoglobin from soon after birth until
death. There are two forms of beta thalassemia: thalassemia minor and
thalassemia major (which is also called Cooley's anemia). There are an
estimated 60-80 million people in the world who carry the beta thalassemia
trait. People
who carry thalassemia in
India
alone number approximately 30 million.
In
India
, beta
thalassemia is very common in the north eastern region with a frequency of
7-64%. High frequency of beta thalassemia trait is also reported in
Gujarat,
Punjab, Tamil Nadu and
West Bengal.
Considering the preponderance of diagnosed Beta thalassemias over Alpha thalassemias,
this database presently holds the relevant data for Beta thalassemias only.
Glanzmann Thrombasthenia
Glanzmann Thrombasthenia is a bleeding disorder characterized by failure of platelet
aggregation and by absent or diminished clot retraction. It can be inherited in
an autosomal recessive manner (
MIM: 273800)
or autosomal dominant manner (
MIM: 187800).
The recessive disease results from mutations in either the gene encoding
platelet glycoprotein GPIIb (ITGA2B) or GPIIIa (ITGB3) genes.
The database currently holds the relevant data for the autosomal recessive
forms of Glanzmann thrombasthenia.
Hermansky-Pudlak Syndrome
It
is a rare autosomal recessive disorder characterised by oculocutaneous
albinism, bleeding, and lysosomal ceroid storage result from defects of
multiple cytoplasmic organelles: melanosomes, platelet-dense granules, and
lysosomes. Hermansky-Pudlak syndrome (HPS) can be caused by mutation in several
genes: HPS1 (
MIM: 604982),
HPS3 (
MIM: 606118),
HPS4 (
MIM: 606682),
HPS5 (
MIM: 607521),
and HPS6 (
MIM: 607522).
HPS2 (
MIM: 608233),
AP3B1 (
MIM: 603401),
DTNBP1 (
MIM: 607145)
and BLOC1S3 (
MIM: 609762).
The database presently holds the data for Hermansky-Pudlak Syndrome 1 and Hermansky-Pudlak Syndrome 9 only.
Megaloblastic Anemia (
MIM: 249270)
Thiamine-responsive
megaloblastic anemia syndrome (TRMA) is characterized by megaloblastic anemia
(onset is between infancy and adolescence, corrected with pharmacologic doses
of thiamine), sensorineural hearing loss (toddlers), and diabetes mellitus (non
type-1; age of onset ranging from infancy to adolescence).
TRMA is inherited in an autosomal recessive manner.
The disorder is caused by a defect in a thiamine transporter protein, SLC19A2.
Purpura (
MIM: 612304)
This
autosomal recessive protein C deficiency resulting from homozygous or compound
heterozygous PROC mutations is a thrombotic condition that can manifest as a
severe neonatal disorder or as a milder disorder with late-onset thrombophilia;
it is a haemorrhagic condition usually associated with sepsis or previous
infection. It occurs mainly in babies and small children.
Hypofibrinogenemia
Hypofibrinogenemia
is a condition characterized by decreased levels of fibrinogen in the blood,
caused by mutations in FGB gene mapped to 4q28 (
MIM: 202400).
Patients suffer from bleeding problems that vary from mild to severe, depending
upon the residual amount of fibrinogen in plasma.
Venous Thrombosis
Venous
thrombosis
is characterized by abnormal formation of
blood clot (thrombus) within a vein,
influenced by both genetic and environmental influences.
It mainly affects the large veins in the lower leg
and thigh. The risk of venous thrombosis increases with
age. Mutation in the JAK2 gene MIM: 147796) is a common genetic cause of venous thrombosis.
Dyskeratosis Congenita (
MIM: 305000)
The
disease mainly affects the integumentary system with a major
consequence being anomalies of the bone marrow. The disorder is
characterised by premature aging with cutaneous pigmentation, dystrophy of the
nails, leukoplakia of the oral mucosa, continuous lacrimation due to atresia of
the lacrimal ducts, often thrombocytopenia, anemia, and in most cases
testicular atrophy. Only males are affected in a pattern consistent with
X-linked recessive inheritance as a result of one or more mutations in the long
arm of the X chromosome in the gene DKC1.
This
may result in specific issues related to dysfunctional rRNA and perhaps a
graver phenotype.
Factor V Deficiency (
MIM: 227400)
Factor
V deficiency
is a rare autosomal recessive coagulation disorder caused by mutations in the
F5 gene (
MIM: 612309).
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