1. Genetic Diseases

2. Genetic Diseases ALBINISM THALASSEMIA SCID [bubble boy syndrome] AGAMMAGLOBULINEMIA SICKLE CELL ANAEMIA HUNTINGTON’S CHOREA

3. . Sickle-Cell Anaemia . • Sickle-Cell Anaemia, also sickle-cell disease, hereditary condition in which haemoglobin, is altered, leading to periodic interruptions in blood circulation. • The RBC in which the altered haemoglobin is contained also changes its shape, from round to crescent (sickle shaped). • The sickle-shaped red cells interfere with normal blood flow by plugging up small blood vessels. The amount of oxygen in the blood also reduced. • The disease is found predominantly in blacks; it also occurs in the Middle East and the Mediterranean area.

4. Sickle-Cell Anaemia • Symptoms: • enlargement of the abdomen and heart, • painful swelling of the hands and feet. • In adolescence, sexual maturation may be delayed. • The affected people exposed to infections and leg ulcers. The patients dies due to damaged heart, kidney, spleen, brain as a result of clogged blood vessels or vascular obstruction.

5. Sickle-Cell Anaemia • Sickle-cell anaemia occurs when an individual inherits autosomal mutant allele Hbs from each parent. • The persons with the genotype HbSHbS suffer with Fatal haemolytic Anaemia • In homozygous condition (HbS HbS) it causes production of abnormal haemoglobin S. • The normal haemoglobin is HbA (HbAHbA) • Persons with heterozygous genotype HbAHbS are said to be carrier and they survive.

6. SICKLE CELL ANAEMIA • Haemoglobin is composed of iron and protein. • Aminoacids are arranged in four polypaptide chains. • They are two identical alpha chains and beta chains. • The glutamicacid in the beta chain of haemoglobin is replaced by valine aminoacid leads to sickle cell anaemia. • As a result the normal shape of the haemoglobin is changed in to sickle shape.

7. Thalassemia The word “thalassemia” is derived from the Greek word for “sea”; the disease was called this because it is more common in Mediterranean origin. However, the disorder is found worldwide. This is an erythroblastic anaemia due to homozygous recessive gene expression in children. It is an inherited form of anaemia in which there is reduced synthesis of one or more of the four globin chains, usually 2αand 2β which make up haemoglobin in RBCs.

8. Thalassemia the main forms in adults being broadly characterized as a- or ß-thalassaemias according to whether the genes for the a or the ß chain are abnormal. • Types of Thalassaemia: • Thalassemia Major – Homozygous – severe form • Thalassemia Minor – Heterozygous – milder form

9. Thalassemia Clinical manifestations: Decrease in the bone marrow activity Splenomegaly (enlarged spleen) Hepatomegaly (enlarged liver) Peripheral haemolysis Normal RBC Thalassemic RBC

10. agammaglobulinemia People who suffer from an unusual deficiency of gamma globulin known as agammaglobulinemia. Patients are deficient in antibodies and may require periodic infusions of gamma globulin to maintain the immune system

11. agammaglobulinemia. • agammaglobulinemia is a recessive gene disease wherein -globulin synthesis fails to occur. • Patient shows great deficiency or total absence of plasma cells and unusual lymph nodes. • The failure of antibody synthesis leads to viral and bacterial infections especially of the chest. • This disease mostly affect boys.

12. Albinism Albinism is an inherited disorder of melanin metabolism leads to absence of melanin in the skin, hairs and eyes. Clinical characteristics: milk white colored skin and marked photophobia. Genes undergo mutation that do not produce particular enzymes for metabolic pathways. In Phenylalanine metabolism, a chain of enzyme mediated reactions occur. Change or absence of this enzyme is due to defective gene results in physiological abnormalities.

14. Albinism In albinism complete lack of melanin pigment causes albino to suffer- Ratio of the sufferer is 1:5000, 1:25000. • Types of albinism: • Total albinism: melanin pigment is completely absent in whole body • Localized albinism: melanin pigment absent in eye [ocular albinism] • Partial albinism: melanin absent in skin hair Recessive genes ‘aa’ do not produce the Tyrosinase enzyme which converts DOPA (3,4- Dihydroxy- phenylalanine) into melanin.

15. HUNTINGTON’s CHOREA Chorea (Greek, choreia, ”dance”), a clinical manifestation of certain diseases, characterized by involuntary, purposeless, spasmodic movements in the entire body. Chorea is most commonly associated with Huntington's disease(also known as Huntington's chorea) Huntington’s disease affects the cerebral cortex which of the brain controls thought, perception, memory, and other complex functions. Huntington’s disease also affects other areas of the brain involved in movement and coordination.

16. HUNTINGTON’s CHOREA Huntington's chorea is caused by autosomal dominant gene located on 4th chromosome – occur at the age between 35 and 40 years. Symptom: uncontrolled jerking of the body is due to involuntary twitching of voluntary muscles. Progressive degeneration of Central nervous system. Gradual mental and physical deterioration. Deterioration of intellectual faculty, depression, occasional hallucination and delusions and other psychological problems. This is incurable.

17. Severe Combined Immuno Deficiency [bubble boy syndrome] It is inherited disease affecting children. gene for this disease called ADA (Adenine Deaminase) is located in the 20th chromosome. • Symptoms: • Lack of Immune defense mechanism against infection due to rapid death of WBC. • The affected child is kept in a sterile bubble. • Unless given bone marrow transplant, the life span of the child is short.

18. Severe Combined Immuno Deficiency [bubble boy syndrome] • The most dangerous group of immune deficiencies resulting from B- and T-lymphocyte malfunction is severe combined immunodeficiency (SCID). • Within 3 to 12 months after birth, infants with SCID develop recurrent bacterial, viral, or fungal infections. • About 30 percent of these infants suffer from an enzyme deficiency known as adenosine deaminase (ADA) deficiency. • In the absence of adenosine deaminase, T- lymphocytes cannot develop normally.

19. PHENYL ALANINE METABOLISM IN MAN

20. Dietry protein Adrenaline and Non adrenaline Tissue protein 3,4,dihydroxy phenyl alanine albinism Phenyl Alanine Tyrosine melanine Thyroxine Phenyl Ketonuria Phenyl Pyruvate Goitre & cretinism Hydroxy phenyl pyruvate Tyrosinosis Homo genetisic acid Alkaptunuria Maley lacto acetic acid Fumaryl aceto aceticacid Fumaric acid and acetoaceticacid

21. PHENYLKETONURIA • The person with genotype pp fail to produce the phenyl alanine hydraxylase enzyme. • This enzyme converts the phenylalanine in to tyrosine. • Metabolic block occur in this reaction due to lack of phenylalanine hydraxylase. • So the phenylalanine concentration accumulates in the blood plasma, cerebrospinal fluid and urine. • This syndrome causes mental deficiency , pigmented patches on the skin, excessive sweating , non pigmented hairs and eyes.

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