Elizabeth was born with low birth weight and dysmorphic features. She developed feeding issues, seizures, and hypocalcemia due to low parathyroid hormone levels. Genetic testing revealed a 22q11.2 deletion consistent with DiGeorge syndrome. She had low T cell counts and poor response to mitogens, indicating complete DiGeorge syndrome. At 6 months she received a thymus transplant, developing T cells and antibody responses over time. However, she later developed immune thrombocytopenia successfully treated with IV gamma globulin.

1. BY
HARSHAD KHAN SIRAJ
GROUP-16
TBILISI STATE MEDICAL UNIVERSITY

2.  ELIZABETH BENNET WAS BORN AT TERM OF AN
UNCOMPLICATED PREGNANCY. SHE HAD A LOW BIRTH
WEIGHT OF 2.1 KG AND DYSMORPHIC FEATURES WERE
NOTED AT THE TIME OF BIRTH INCLUDING LOW SET EARS
AND A SMALL MOUTH WITH UNDERSIZED LOW JAWS.
ELIZABETH DEVELOPED FEEDING DIFFICULTIES AFTER 2
DAYS OF BIRTH,RAPID FATIGUE,CONGENITAL HEART
DEFECTS CHARACTERIZED BY SINGLE OUTFLOW OF BLOOD
INSTEAD OF TWO- AORTA AND PULMONARY ARTERY. AT
DAY 4 OF AGE ELIZABETH DEVELOPED SEIZURES. SHE WAS
FOUND TO HAVE VERY LOW LEVELS OF CALCIUM AND WAS
TREATED WITH CALCIUM AND VITAMIN D. HER
HYPOCALCEMIA RESULTED FROM VERY LOW
PARATHORMONE IN HER BLOOD, A HORMONE MADE BY
PARATHYROID GLAND AND IT IS CRITICAL FOR
REGULATING CALCIUM HOMEOSTASIS IN THE BODY.

3.  ELIZABETH UNDERWENT CARDIAC SURGERY
FOR REPAIR OF HER HEART DEFECTS. NO
THYMIC TISSUE WAS FOUND
INTRAOPERATIVELY. AFTER SUCCESSFUL
SURGERY, GENETIC STUDIES WERE DONE;
THESE REVEALED A NORMAL KARYOTYPE,
WHICH EXCLUDED MAJOR CHROMOSOMAL
REARRANGEMENTS. HOWEVER WITH THE HELP
OF FISH WE FOUND TO HAVE DELETION OF
22q11.2 CONSISTENT WITH THE DIAGNOSIS
OF DIGEORGE SYNDROME.

4.  AT AN IMMUNE ELEVATION AT 2 WEEKS OLD,
ELIZABETH’S ABSOLUTE LYMPHOCYTE COUNT
WAS LOW FOR HER AGE,WITH 560 CELLSчl-
1(3000 LYMPHOCYTES PER чl-1).SHE HAD
ALMOST NO CD3+ T CELLS, WHILE NOS OF CD-
19 AND B CELLS WERE FOUND TO BE NORMAL
FOR HER AGE. HER PERIPHERAL BLOOD
MONONUCLEAR CELLS (PBMC) RESPONDED
POORLY TO CONCLAVIN A AND
PHYTOHEMEAGGLUTIN WHICH IS A INDICATOR
FOR POOR T-CELL FUNCTION. HER SIGNIFICANT
LOSS OF T-CELL FUNCTION IS DIAGNOSED AS
COMPLETE DIGEORGE SYNDROME. IT IS FOUND IN
1% OF THE POPULATION.

5.  ELIZABETH WAS STARTED ON PROPHYLATIC
ANTIBIOTICS TO PREVENT INFECTION WITH
OPPUTRTUNISTIC PATHOGEN PNEUMOCYTIS JIROVECI.
AT 6 MONTHS OF AGE SHE RECEIVED A THYMUS
TRANSPLANT INTO HER RIGHT LEG QUADRICEPS
MUSCLE. A BIPOSY OF THYMUS GRAFT, PERFORMED A
FEW MONTHS AFTER TRANSPLANT, SHOWED
SIGNIFICANT PRESENCE OF THYMOCYTES WITH A
TRANSPLANTED THYMIC TISSUE. ONE YEAR OF
TRANSPLANT ELIZABETH DEVELOPED A SIGNIFICANT
NO OF T CELLS RESPONDED TO MITOGENS,
ALTHOUGH SHE DID NOT REACH THE NORMAL
COUNT. ELIZABETH MOUNTED PROTECTIVE ANTIBODY
RESPONSE AGAINST TETANUS TOXOID, HEMOPHILUS
INFLUENZA B AND STREPTOCOCCUS PNEUMONIA.

6.  AT 6 YEARS OLD ELIZABETH DEVELOPED PURPLE
BRUISES(PURPURA) AND PINPOINT RED LESIONS(
PETETCHIAE) ON HER SKIN. SHE WAS FOUND TO
HAVE LOW PLATELET COUNT OF 15,000чl-1 (
NORMAL 1,50,000-3,00,000чl-1). THIS WAS DUE
TO DESTRUCTION OF HER PLATELETS BY
ANTIBODIES, RESULTING IN INSUFFECIENT BLOOD
CLOTTING AND THEREFORE BLEEDING INTO HER
SKIN CALLED IMMUNE THROMBOCYTOPENIA. SHE
WAS SUCCESSFULLY TREATED WITH I.V GAMMA
GLOBULIN.

7.  A CONGENITAL DEFECT ARISING IN THIRD
AND FOURTH PHARYNGEAL POUCH RESULTS
IN DIGEORGE SYNDROME.
 IT IS CAUSED DUE TO DELETION OF 22q11.2
CAUSES MUTION IN TBX 1 GENE,
 WHICH PLAYS A IMPORTANT ROLE IN
DEVELOPMENT OF PHARYNGEAL POUCH
 POUCH 3 AND POUCH 4 IS RESPONSIBLE FOR
FORMATION OF THYMUS AND PARATHYROID
GLAND

9.  THE MAIN IMMUNO PATHOGENESIS INVOLVES
T CELL AND CALCIUM DEFICIENCY.
 THE CAUSE FOR THIS DEFICIENCY IS THE
UNDERDEVELOPMENT OF THYMUS AND
PARATHYROID GLAND
 THIS SYNDROME IS CLASSIFIED INTO
 PARTIAL DIGEORGE SYNDROME
 COMPLETE DIGEORGE SYNDROME

10.  PARTIAL DIGEORGE SYNDROME RESULTS
FROM MILD TO MODERATE DYSFUNCTION OF
THYMUS GLAND AND IT IS NOT LIFE
THREATENING
 COMPLETE DIGEORGE SYNDROME RESULTS
FROM THE SEVERE DYSFUNCTION OF
THYROID GLAND AND IT IS OFTEN LIFE
THREATENING.
 A CONTINUOUS MEDICAL CARE IS NEEDED.

11.  UNDER NORMAL CONDITIONS T CELL IS
PRODUCED IN THE BONE MARROW AND GETS
MATURED IN THE THYMUS.
 BUT IN DIGEORGE SYNDROME THERE IS AN
UNDER DEVELOPED THYMUS.
 AND MATURATION OF T CELL IS REDUCED OR
COMPLTELY STOPPED DEPENDING ON HOW
BAD IS THYMUS AFFECTED

13.  OTHER IMPORTANT GLAND ION OUR BODY IS
PARATHYROID GLAND.
 PARATHYROID GLND IS IMPORTANT FOR
CALCIUM PRODUCTION IN OUR BODY.
 DUE TO UNDER DEVELOPED PARATHYROID
GLAND WILL HAVE HYPOPARATHYROIDISM IS
COMMON LEADING TO SEIZURES AND
SHAKING (TREMORS).

15. DEVELOPING
ORGANS
PHARYNGEAL
POUCH
GENE TBX1
POUCH 3
THYMUS
INFERIOR
PARATHYROID
GLAND
POUCH 4
SUPERIOR
PARATHYROID
GLAND

16.  CLEFT PALATE

17.  LONG FACE
 STRONG TEETH
 BROAD NOSE

18.  A DIAGNOSIS OF DIGEORGE SYNDROME IS
BASED PRIMARILLY ON A LAB TEST THAT CAN
DETECT THE DELETION IN CHROMOSOME 22.
 RESPONSE TO MITOGEN
PHYTOHEMEAGGLUTIN AND CONCLAVIN A
HELUS US TO FIND ACTION OF T-CELL
FUNCTION.
 LEVEL OF T-CELL HELPS US TO DIAGNOSE
DIGEORGE SYNDROME.

19.  THERE IS NO CURE FOR DIGEORGE
SYNDROME.
 BUT THYMUS TRANSPLANT AND SURGERY OF
HEART CAN BE MADE EFFECTIVE.
 FOR HYPERPARATHYROIDISM VITAMIN D AND
CALCIUM SUPPLIMENT MUST BE TAKEN.