by A CASE SCENARIO Dr.Syed Hunain Riaz P.G M2 Slide 001

HISTORY

Case History A 14 years old boy of very low socioeconomic background presented with 1. Shortness of breath About 10 years 2. Generalized weakness -----About the same duration Slide 002

History of presenting illness The boy was was in his usual state of health when he was about 4 years old when he gradually developed shortness of breath. It was exertional in nature. He did not have orthopnea or PND. There is h/o palpitations associated with the dyspnea. No h/o chest discomfort, body swellings or hemoptysis. No h/o syncopal events. H/o yellowish discoloration of eyes for the last many years, no h/o abdominal distention, no h/o unconsciousness He started to develop generalized weakness and as such was unable to perform simple activities.

No h/o blood in stools, no h/o alternating bowel habits or worms in stool. PAST HISTORY Non/diabetic, non/diabetic, non-asthmatic. Has had blood transfusions three times over period of 10 years. FAMILY HISTORY No h/o diabetes, IHD, asthma or TB in the family, no h/o any disease in his siblings. Has 3 brothers, all older than him, all healthy.

DRUG HISTORY No h/o any drug intake and no allergies to any medicine SOCIOECONOMIC HISTORY Belongs to a lower class family who earn their bread by farming

EXAMINATION

General Physical exam A young boy of average built with prominent facial bony features ( slightly protuding forhead, prominent zygomatic area ) well oriented, sitting comfortably in bed. Vitals and Exam findings : BP: 90/50 mmHg Pulse: 90/min R/R: 18/min Temp: Afebrile Jaundice: ++(lime colored) Pallor: +++ Cyanosis: - Clubbing: -

Lymph nodes: - JVP: Not Raised Pedal edema: - Palmar erythema: - Neck veins: Not distended Koilonychia: - 2 shallow ulcers(2-3 cm each) with clean margins and yellowish discharge on dorsum of right foot.

Marked pallor on Exam

Systemic Exam Cardiovascular: Apex beat in left fifth ICS, normal in character Soft S1 and S2, soft A2 and loud P2 Pansystolic murmur heard in mitral area, radiating to axilla. Pansystolic murmer heard in tricuspid area, increasing in intensity with inspiration

Gastrointestinal: Abdomen soft, non tender, no pulsations or veins visible Upper border of liver in right 5th ICS, lower edge palpated about 4 fingers below right hypochondrium, extending into the epigastrium, non-tender, and smooth surfaced. Liver span about 18 cm Spleen palpated 2 fingers below left hypochondrium towards the umbilicus, non tender and smooth surfaced. No free fluid on in abdomen on examination

Hepatosplenomegaly

CNS: Grossly intact Respiratory: Normal chest shape and movements Chest expansion normal NVB with no added sounds Muskoloskeletal: NAD

Differential Diagnosis based on History\Exam Anemia ( Iron deficiency? Hemolytic? ) Lymphoproliferative disorder? Valvular heart disease ( leading to long standing anemia )?

INVESTIGATIONS

CBC with peripheral smear Hb: 3.4 g/dl Rbc: 1.3 ×10^12/l Hematocrit: 8% MCV: 75 fl MCH: 24 pg N ( ) MCHC: 31 g/dl N ( ) Platelets: 265×10^9/l WBC: 7×10^9/l Neutrophils, monocytes, eosinophils, basophils and lymphocytes all within normal limits Retic count: 1%

RBC morphology: Hypochromia: +++ Microcytosis: ++ Anisocytosis: +++ Poikilocytosis: +++ Target cells: ++ ESR: 150 mm/1 st hour LDH: 550 IU ( upto 450 ) URINE C/E: Normal pH, no sugars, no proteins. No hemoglobinuria, no hemosiderin pigments. Urobilinogen normal, bilirubin not detected No blood cells.

Liver function tests: Bilirubin total: 2.1 mg/dl Bilirubin direct: 1.3 ( ) Bilirubin indirect: 0.8 ( ) ALT: 56 IU AST: 41 IU ALK phosphatase: 394 IU/l ( ) Proteins: 5.4 g/dl Albumin: 2.7 Globulin: 2.7 PT: 16/13 aPTT: 36/33 Renal function tests: Urea: 17mg/dl Creatinine: 0.5 mg/dl

Stool exam: No ova or parasites, negative for occult blood. USG ABDOMEN\ PELVIS: 18.5 cm Liver with normal echotexture, intra/extrahepatic biliary channels normal, no focal lesion Spleen 16 cm ( enlarged ) KUB normal No fluid or lymph nodes seen in peritoneal cavity CHEST XRAY: Enlarged heart, lungs and costophrenic angles clear ECG: Normal axis and rhythm, symmetric T-wave inversions in anterior chest leads

Echocardiography: Mild dilatation of cardiac chambers Slightly increased pulmonary arterial pressure Normal valves but functional MR and TR present Normal biventricular function

WHAT’S LIKELY AND WHAT TO DO?

Based on clinical and investigation data, there was a high suspicion of a long standing hemolytic anemia (extravascular hemolysis), specifically “ THALASSEMMIA”, so a hemoglobin electrophoresis was ordered…..

Hemoglobin Electrophoresis: HbA: 53.4 % HbF: 44.2 % HbA2: 2.4 %

CONCLUSION The final diagnosis was: ß-THALASSEMIA INTERMEDIA/ MAJOR

Thalassemias A heterogenous group of inherited disorders of hemoglobin synthesis resulting decreased or absent hemoglobin chains synthesis Classified into alpha and beta thalassemias. Varied pattern of inheritance Decreased synthesis of ß-chains result in over production of alpha chains, and also gamma and delta chains leading to the finding of fetal and HbA2 type of hemoglobin in ß-thalassemias

Treatment Thalassemia major\ intermedia patients are treated on the following lines: BLOOD TRANSFUSIONS CHELATION THERAPY ( DESFERIOXAMINE ) ALLOGENIC BONE MARROW TRANSPLANTATION Splenectomy may be needed if BMT is not feasible for reducing the RBC destruction in the spleen

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