[CIS PIDD] [cis-pidd] Peruvian 10-yr-old girl with recurrent severe pancytopenia, and physical/mental retardation

[Juan Carlos Aldave Becerra]

Dear professors,
I evaluated this week a 10 yr-old girl with a very puzzling clinical picture. I describe below the clinical history.
The main features are:- Recurrent severe pancytopenia, predominantly
of the myeloerythroid lineage.

- Physical
and mental retardation with cerebral atrophy and microcephaly.

- Residual bronchiectasis
I would appreciate your expert insights and suggestions.Thank you very much.
Sincerely,
Juan Carlos Aldave, MDAllergy and Clinical ImmunologyHospital Nacional Edgardo Rebagliati MartinsLima, Peru
-----------------------------Girl, 10 yrs of ageDate of birth: August 11th
2004 FAMILY HISTORY:-      
No family members with suspicion of PID.-      
No
siblings, healthy parents (50 and 51 yrs of age).-      
The
maternal 1st grade
female cousin of the patient's mother died due to "aplastic bone marrow".-      
No
consanguinity. PERSONAL HISTORY:-      
Intrauterine growth retardation-      
Weight
at birth=1,720 g (gestational age=7.5 months)-      
No
adverse reactions to live vaccines, including BCG-      
Current
weight=18 kg (below P3
for age)-      
Current
height=114 cm (below P3
for age)-      
Local
adverse reactions to mosquito bites. CURRENT DISEASE:-      
Apparently
healthy up to 11 months of age.
-      
From
11 months of age: recurrent episodes of severe thrombocytopenia (up to less
than 1,000 platelets/μL), neutropenia (up to less than 100 neutrophils/μL) and anemia (up to 6 g/dL, low
reticulocyte counts); in some episodes there also was mild-moderate lymphopenia
(~1,000 lymphocytes/μL). Please see the table below for
detailed CBCs during some episodes).·      Duration of the episodes: 3 to 4
weeks, and resolve spontaneously.·      Frequency of the episodes: every 7
to 21 months.·      Total number of episodes in the
patient's life: twelve (February 2005, September 2005, April 2006, December
2006, September 2008, February 2010, September 2010, July 2011, November 2012,
July 2013 [only thrombocytopenia], October 2013 [only neutropenia], the last episode started 2 weeks ago).·      Clinical features during the
episodes:§  Total alopecia (hair grows again
after the episodes), high fever, vomiting, hiporexia, diarrhea, petechiae, mucosal
bleeding, oral candidiasis, elevated ESR (~40 mm/h).§  Parents note that despite all these
clinical features the patient does not appear acutely ill during the episodes.§  No lymphadenopathies, no
hepatosplenomegaly·      Response to therapies:§  No response to G-CSF and IVIG.§  Patient was treated with high-dose
systemic corticosteroids during the episode of November 2012 and the father
noticed that there was good response (the episode lasted shorter).·      Complications during the episodes:§  'Bacterial' pneumonia (no
microorganisms were isolates) during the episode of April 2006, complicated
with pleural effusion and residual bronchiectasis.§  Pneumonia, positive blood culture to
Pseudomona aeruginosa.
-      
Between
episodes the patient has not had any severe or opportunistic infection.-      
Bronchiectasis
from 2 yrs 6 months of age, persistent production of sputum.-      
Growth
and mental retardation that was noticed at the first episode of pancytopenia (11 months of age). Example: she walked
at 4 years of age. Current neurological and physical development appears as
from a 6-yr-old child.-      
Microcephaly.-      
Apparently
normal facies. WORK UP: 
 
  
  CBC counts at birth and during the 1st
  episode
  
 
 
  
   
  
  
  13-3-2004
  
  
  12-2-2005
  
  
  14-2-2005
  
  
  16-2-2005
  
  
  18-2-2005
  
  
  20-2-2005
  
 
 
  
   
  
  
  2 days of age
  
  
  1st episode of thrombocytopenia,
  neutropenia and anemia
  
 
 
  
  Platelets (per μL)
  
  
  200,000
  
  
  68,200
  
  
  60,500
  
  
  117,000
  
  
  275,000
  
  
  412,000
  
 
 
  
  Hemoglobin
  
  
  17.1
  
  
  6.8
  
  
  11.9
  
  
  12
  
  
  12.9
  
  
  13.7
  
 
 
  
  WBC
  
  
  9,800
  
  
  4,900
  
  
  8,340
  
  
  6,350
  
  
  11,700
  
  
  10,400
  
 
 
  
  Neutrophils
  
  
  45%
  
  
  2%
  
  
  5%
  
  
  10%
  
  
  27%
  
  
  8%
  
 
 
  
  Banded
  
  
  1%
  
  
  0%
  
  
  1%
  
  
  3%
  
  
  8%
  
  
  2%
  
 
 
  
  Lymphs
  
  
  44%
  
  
  94%
  
  
  85%
  
  
  68%
  
  
  50%
  
  
  77%
  
 
 
  
  Eosinophils
  
  
  1%
  
  
  4%
  
  
  4%
  
  
  0%
  
  
  2%
  
  
  1%
  
 
 
  
  Basophils
  
  
  1%
  
  
  0%
  
  
  0%
  
  
  0%
  
  
  0%
  
  
  0%
  
 
 
  
  Monocytes
  
  
  8%
  
  
  0%
  
  
  5%
  
  
  18%
  
  
  12%
  
  
  12%
  
 
 
 
  
  CBC counts during the 2nd and 3rd
  episodes
  
 
 
  
   
  
  
  14-9-2005
  
  
  15-9-2005
  
  
  06-4-2006
  
  
  10-4-2006
  
  
  22-4-2006
  
  
  29-4-2006
  
 
 
  
   
  
  
  2nd episode
  
  
  3rd episode
  
 
 
  
  Platelets (per μL)
  
  
  18,600
  
  
  106,000
  
  
  4,000
  
  
  15,000
  
  
  14,000
  
  
  250,000
  
 
 
  
  Hemoglobin
  
  
  10.1
  
  
  9.7
  
  
  7.2
  
  
  NA
  
  
  9
  
  
  11. 1
  
 
 
  
  WBC
  
  
  2,540
  
  
  2,190
  
  
  1,000
  
  
  800
  
  
  4,500
  
  
  19,200
  
 
 
  
  Neutrophils
  
  
  3%
  
  
  1%
  
  
  0%
  
  
  0%
  
  
  29%
  
  
  46%
  
 
 
  
  Banded
  
  
  0%
  
  
  0%
  
  
  0%
  
  
  0%
  
  
  12%
  
  
  16%
  
 
 
  
  Lymphs
  
  
  87%
  
  
  95%
  
  
  96%
  
  
  49%
  
  
  46%
  
  
  27%
  
 
 
  
  Eosinophils
  
  
  0%
  
  
  4%
  
  
  3%
  
  
  0%
  
  
  1%
  
  
  0%
  
 
 
  
  Basophils
  
  
  0%
  
  
  0%
  
  
  0%
  
  
  0%
  
  
  0%
  
  
  0%
  
 
 
  
  Monocytes
  
  
  6%
  
  
  0%
  
  
  0%
  
  
  0%
  
  
  10%
  
  
  2%
  
 

Immunologic testing (during an episode):-      
July 27, 2011: IgG=1127, IgA=137, IgM=127 mg/dL, IgE=506 UI/mL
Immunologic testing (between episodes):-      
May 31, 2006: IgG=2052, IgA=119, IgM=162 mg/dL, IgE=62 UI/mL-      
September 19, 2007: IgG=980, IgA=68, IgM=71 mg/dL, IgE=62 UI/mL-      
May 31, 2006: CD3+ cells=14,028 (68% HLA-DR +); CD4+ T cells=2,304; CD8+ T cells=10,688;
CD19+ cells=450.-      
August 28, 2007: WBC=6,300;
lymphs=4,095; CD3+
cells=2,079 (most HLA-DR and CD25 negative); CD4+ T cells=1,134; CD8+ T cells=882;
CD19+ cells=1010; CD56+
cells= 378/mm3.-      
Negative
autoantibody panel (ANA, anti-DNA, ANCA, anti-Sm, anti-RNP, anti-SS-A,
anti-SS-B, anticardiolipin, lupus anticoagulant).-      
C3
and C4 complement proteins: normal levels.
Infectious disease testing:-      
Negative
testing for acute EBV, CMV, parvovirus B19, herpes simplex, toxoplasma,
Salmonella typhi and Brucella sp infection.-      
Negative
testing for viral hepatitis.-      
Negative
RPR.
Hematologic testing:-      
Reticulocyte count <1.5%.-      
Haptoglobin=344 mg/dL (normal levels: 30-200).-      
LDH=662 mg/dL (normal levels: 58-158).-      
Serum iron=318 mg/dL (normal levels: 58-158).-      
Serum transferrin=118 mg/dL (normal levels:
250-400).
Genetic and metabolic testing:-      
Serum glucose, urea, creatinine,
transaminases, albumin and electrolyte levels: within normal limits-      
Ferritin >1,500 mg/dL-      
Normal
newborn screening tests for hypothyroidism and phenylketonuria.-      
Karyotype:
normal 46,XX-      
Diepoxybutane
(DEB) test: no chromosomal breakages.-      
No
detection of urinary abnormal metabolites.-      
Aminoacid
chromatography: normal
Histology results:-      
Bone
marrow smear (during an episode; 20/9/2005): severe bone marrow hypoplasia
(lymphocytes=62%).-      
Bone
marrow smear (during an episode; 22/9/2005): reduced myeloerythroid lineage.-      
Bone
marrow smear (between episodes; 25/5/2006): reactive bone marrow.-      
Bone
marrow biopsy (between episodes; 25/5/2006): normal findings.
Imaging results:-      
Brain
US (23-3-2004): no abnormalities.-      
Brain
CT (03-9-2004): bilateral frontoparietal cortical atrophy.-      
Brain
MRI (14-9-2004): dysplastic cranium; retardation of myelination; hypoplastic
or developing brain.-      
Chest
CT (12-5-2006): inflammatory process in the parenchyma of the left lung
base; loculated pneumothorax; consolidation in the right lung base.-      
Large bone and crania X-rays: normal. DIAGNOSIS:-      
Recurrent severe pancytopenia, predominantly
of the myeloerythroid lineage.-      
Physical
and mental retardation with cerebral atrophy and microcephaly.-      
Bronchiectasis 		 	   		   		 	   		   		 	   		  
---
The CIS-PIDD listserv is supported by the Clinical Immunology Society
The science & practice of human immunology

P: +1.414.224.8095
E: info at clinimmsoc.org

Not a member of CIS? Please visit www.clinimmsoc.org to join!

You are currently subscribed to cis-pidd as: pagid at list.clinimmsoc.org.
To unsubscribe click here: http://lm.clinimmsoc.org/u?id=183939985.3ea13d40a15475ac00ebbd9cd8a37d6d&n=T&l=cis-pidd&o=44864664
or send a blank email to leave-44864664-183939985.3ea13d40a15475ac00ebbd9cd8a37d6d at lists.clinimmsoc.org
-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://seven.pairlist.net/pipermail/pagid/attachments/20140510/69b8baf7/attachment-0001.htm>