Dr Theresa Raju, Dr Rema, DrGayathri DrSuchithra Sivadas Dr C Jayakumar, AIMS Pediatrics
Eleven year old male presented with high grade intermittent fever since 10 days after treatment from primary care as haematological anomalies was detected
No history of cough, breathing difficulty, vomiting, loose stools, abdominal pain, weight loss, joint pain or joint swelling. The child also had history of on and off skin bruising for the last 6 months
. Clinically he had pallor but no icterus, cyanosis, clubbing, lymphadenopathy, odema. There were no café-au-lait spots. Head to foot examination revealed deep set eyes.
Anthropometry done showed head circumference:51cm
weight:30kg <ess than 3rd centile) and height:128cm(less than 3rd centile
Systemic examination was normal.
Labs: TC:2.71K/Ul, N:4.7%, L:88.6%, Hb: 10.5, PLT: 85Ku/ml,
SGOT:20.5IU/L, SGPT:18.8IU/L,
ALP:IU/L normal
IgM leptospirosis , IgM Scrub typhus, dengue panel, EBV IgM were negative.
Blood and urine culture were negative.
Peripheral smear done showed Macrocytic anemia with leucopenia and thrombocytopenia. Very severe neutropenia. Platelets: singly scattered. No blast cells
ANC:76.5cells/mm3,
ALC:2397 cells/mm3,
AMC:76.5cells/mm3
• ANA:2+
• Complements and ds DNA ELISA done were normal
• Rheumatology ruled out autoimmune disease.
Flow cytometry: IMPRESSION: No definite immunophenotypic evidence of acute leukemia/ bone marrow involvement B/T cell Non-Hodgkin Lymphoma
COMMENTS:9.9% lymphocytes and rest maturing myeloid cells were seen. Mature B Cells are polyclonal and there is no evidence of atypical antigen present. T cells show normal levels of T cells antigens and there is no evidence of subset restriction.
Bone marrow aspiration showed pauciparticulate fat rich particles and sparsely cellular imprints show predominantly lymphocytes.
Bone marrow biopsy showed no evaluable bone marrow.
Karyotyping done showed normal male chromosome complement in all cells.
PNH flow cytometry was negative.
Stress cytogenetics was positive -sensitive to mitomycin C induced chromosome damage/aberrations.
Genetic consultation was availed and genetic counselling was given regarding the diagnosis of bone marrow failure possibility of being inherited/acquired and that the child may require bone marrow transplantation if inherited or if there is poor response to therapy.
The child was started on Inj posaconazole, Tab Eltrombopag,
Levofloxacin prophylaxis and other supportives .1 pint RBC and platelet rich plasma :3RDP was transfused.
WES done showed homozygous deletion of 4.94Kb in chromosome 16 comprising of exons 32-36 of FANCA gene leading to Fanconi Anemia complementation group A. Posaconazole and Levofloxacin was stopped after neutrophil recovery. Currently the child is on Romiplostim since 1 month. The child is also planned for Allogenic stem cell transplantation.
Fanconi anaemia is the most common Inherited bone marrow failure syndrome(BMFS).
Here the cells cannot properly repair interstrand crosslinks of DNA. It is mostly AR inherited. FANCA is the most common type. Few clinical findings include deep set eyes, short stature, absent or hypoplastic thumbs,hypospadias,microcephaly,ptosis,PDA,strabismus.Investigation include CBC,DC,PT and PTT, Bone marrow examination, chromosome breakage testing and WES which is used to confirm the diagnosis
Treatment include Allogenic hematopoietic stem cell transplantation, androgen therapy, transfusions and growth factors.
Take home message: A systemic approach should be adopted in laboratory investigations for the cause of anemia. Red cell indices and reticulocyte response remain the most useful tools for evaluation of anemia