Severe DiGeorge Syndrome

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Severe DiGeorge Syndrome

• Carolina Díaz Gallardo
• University of Chile Clinical Hospital

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Patient History

• Female patient 4 months old
• Previous medical history normal weight full
  term newborn antenatal diagnosis of congenital
  cardiopathy
• Her parents are not consanguineous
• 3 healthy siblings without clinical history of
  recurrent infections

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Patient History (continued)

• She was operated on at 18 days old post-natal
  diagnosis Truncus arteriosus type I
  In-terventricular communication and patent
  foramen ovale
• Good clinical evolution Discharged 10 days
  after the cardiac surgery
• At home difficulty for feeding nausea stridor
  dysphonia central cyanosis and fever
• ER admitted with the diagnosis of probable
  nosocomial pneumonia and larynx stridor post
  extubation

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Hospitalization 1 for Hypocalcemic Seizure

• At ER episode of tonic-clonic seizures
  managed with lo- razepam
• Physical examination tachycardia respiratory
  rate oxy- gen blood saturation 96
  (0.5l/min)
• Failure to thrive low implantation ears
  micrognathia wide nasal bridge holosystolic
  murmur
• Hemogram - Hematocrit 282 Hemoglobin 92
  mg/dl
• - WBC 9900 cells/mm3 76
  neutrophils 9 lymphocytes
  (891) - Platelet count 436000 cells/mm3
• Serum electrolytes normal range
• Serum Calcium 0.48 mmol/L (1.12-1.32 mmol/L)
• Chest X-ray no signs of lung condensation
  thymus aplasia

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Hospital Course

• Probable diagnosis
• - DiGeorge syndrome with symptomatic
  hy-pocalcemia
• Immediate management with iv calcium gluconate
• Endocrinologists PTH 4 mg/dl and they
  prescribed calcitriol 0.125 mg qd.
• Calcium serum levels returned to normal and she
  was discharged

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Hospitalization 2 Immunology Evaluation

• At home problems with oral tolerance
• ER visit recurrence of seizures
• Ca 0.6 mmol/L readmitted and iv calcium
  supple-mentation was restarted
• Hemogram - Hematocrit 292 Hb 94 mg/dl
  
• - WBC 5400 cells/mm3 75
  neutrophils
• 7 lymphocytes
  (378)
• Immunologists were consulted new lab exams

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Immunologic Studies (Age 2 months 25 days )
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Further Immunologic Studies and Management

• FISH for 22q11 deletion was ordered The results
  were negative in 2 occasions
• TBX1 gene study is still pending
• proliferating T cells was determined (CFSE)
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• Prophylactic therapy TMP/SMX flucona-
  zole and acyclovir
• IV gammaglobulin

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• Intercurrent infectious episodes
• Acute diarrhea bloody stools
• Abdominal X-ray showed pneumatosis
  ampi-cillin amikacin metronidazole
• Unknown origin fever
• Increase in inflammatory markers CRPgt100
  cloxacillin and cephotaxim with bad results
  cephotaxim plus vancomycin
• Definitive diagnosis Sepsis associated to
  cen-tral venous catheter with cultures MRSA
• On ultrasound a small vegetation on the
  endo-cardic surface Infective endocarditis
  ami-kacin plus vancomycin

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Most Recent Immunologic Studies (Age 3½ m/o)
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Summary

• 4 m/o term female with classical Di-George
  Syndrome triad and a SCID phenotype
• Normal FISH for 22q11.2
• Possibilities
• 10p deletion (DGS II allele)
• Mutation limited to TBX1
• Other gene mutation

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CHILE