DEPARMENT OF BIOCHEMISTRY LABORATORY

SHAH, NITI KUMAR CASE-5 SAPKOTA,RAJITARAJBANSI,BIJAYPATEL,BIR BAHADURRAI,NAKULSAH,PANKAJSAID,ABDIKANISHIRE,AHMEDROSAURO GOLDEE MEIRCHARLINE S. PEPITO

GROUP – FIVE SECTION - F

A 15-year old African-American female presents to the emergency room with complaints of bilateral thigh and him pain. The has been present been present for one day and is steadily increasing in severity. Acetaminophen and ibuprofen have not relieved her symptoms. she denies any recent trauma or excessive exercise . She does report feeling fatigued and has been having burning with urination along with urinating frequently. She reports having similar pain episode in the past, sometimes requiring hospitalization. On examination, she is afebrile (without fever) and

CASE

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In no acute distress. No one in her family has similar episode. Her conjunctiva and mucosal membrane are slightly pale in coloration. She has nonspecific bilateral anterior with no abnormalities appreciated. The remainder of her examination is completely normal. Her white blood count is elevated at 17,000/mm3, and her hemoglobin(Hb) level is decreased at 7.1g/dl. The urinalysis demonstrated an abnormal number of numerous bacteria.

What is likely diagnosis? What is the molecular genetics behind

thus disorder ? What is the pathophysiology mechanism

of her symptoms ?

Answers

Most likely diagnosis: Sickle cell disease (pain crisis).

Biochemical mechanism of disease: Single amino acid substitution on hemoglobin beta chain, inherited in an autosomal recessive fashion (1 of 12 African Americans in United States are carriers of the trait).

Pathophysiologic mechanism of symptoms: The sickled red blood cells cause infarction of bone, lung, kidney, and other tissue from vasoocclusion.

Clinical correlation

This 15-year-old female’s description of her pain is typical of a sickle cell pain crisis.

This case is consistent with a urinary tract infection, indicated by her symptoms of urinary frequency, and burning with urination (dysuria).

Her white blood cell count is elevated in response to the infection. The low hemoglobin level is consistent with sickle cell anemia.

Discussion

Sickle cell anemia is a disease in which the body makes sickle-shaped red blood cells

Red blood cells contain an iron-rich protein called hemoglobin. This protein carries oxygen from the lungs to the rest of the body

Normal hemoglobin has four subunits called globins. Adult hemoglobin has two a (a1 and a2) and two b (b1 and b2) globin chains.

Each globin chain has an associated heme prosthetic group, which is the site of oxygen binding and release.

Pathophysiology

Sickle cell anemia results from the nonconservative substitution of valine for glutamate at residue 6 (Val-6) in the b-chain of hemoglobin.

The β-globin gene is found on the short arm of chromosome11.

The association of two wild-type α-globin subunits with two mutant β-globin subunits forms haemoglobin S (HbS).

Under low-oxygen conditions (being at high altitude, for example), the absence of a polar amino acid (Glutamate) at position six of the β-globin chain promotes the non-covalent polymerisation (aggregation) of haemoglobin, which distorts red blood cells into a sickle shape and decreases their elasticity.

Loss of oxygen.

Polymers or rigid rodsleading to sickled RBCs

RBCs Stick to blood vessels

Stasis

Hypoxia

Pain ( vaso-occlusive crisis)

Diagnosis

Diagnosis of sickle cell disease and sickle cell trait can be done through blood testing.

A special technique is also used called hemoglobin electrophoresis

Hemoglobin Electrophoresis: A small blood sample is taken and sent to a laboratory where the percentage of normal and abnormal hemoglobin is measured.

Signs and symptoms

The most common symptom of anemia is fatigue (feeling tired or weak). Other signs and symptoms of anemia include:

Shortness of breath Headaches Coldness in the hands and feet Jaundice (a yellowish color of the skin or whites of the

eyes) Hand –foot syndrome due to the blockage of blood

vessels in the hands and feet. Organs like spleen and liver also damages.

Treatment

Treatment of sickle cell anemia includes: pain medications (for example, morphine). Anti-inflammatory medications (for example,

ibuprofen). Antibiotics for infection. Intravenous or oral fluids. Transfusions of red blood cells are given for

anemia. Stem cell transplant is performed in young

patients with severe sickle cell disease.

Prevention

Genetic screening Testing for sickle cells in babies.

Chronic vill samplingAmniotic fluid samplingFetal blood samplin

Daily penicillin for newborn babies with the disease.

Prognosis

Patients receiving proper medical care may learn to lead relatively normal life.

Average life expectancy of patients suffering from is

Male = 42 yearsFemale = 48 years