AN INTERESTING CASE OF ANAEMIA IN SIBLINGS

Dr.S.MURUGARAJAN,department of paediatrics,railway hospital, perambur.

PRESENTING COMPLAINTS: A 13yr old adolescent girl presenting with

complaints of –loss of appetite – 3 weeksTiredness - 3 weeks Yellow discoloration of eyes – 2 weeks

She has been refusing food and has been feeling tired after minimal exertion since 3 weeks.

Since 2 weeks her eyes appear yellow, she was passing

- urine in normal colour and frequency,- stools normal .

FEW NEGATIVE HISTORY:

No history of :

-fever , rash , Joint Pain- vomiting- abdominal Pain- Breathlessness- blood in stools,

- suggestive of malabsorption- or any other significant complaints.

PAST HISTORY:

Evaluated in 2008 for similar illness in local hospital.

Episodes of pallor and jaundice observed once in 5 – 6 months since then.

No history of blood transfusion.

FEW MORE HISTORY:

Antenatal History : Uneventful Natal and Postnatal History : FT NVD,

Birth weight : 2.75, No history of neonatal jaundice or any other illness in neonatal period.

Family History :37 36

13 10 8

Diet History : Non – Veg

Taking Fe and FA tablets for the past 6 months prescribed by the local doctor.

Development History:Age appropriate millstones attained, Good in studies, not attained menarche.

Expected

Observed

Proteins 65g 40 g

K Calories 2060kcal

1900k cal

CLUES ON EXAMINATION:

Vitals Stable :Pallor+,Icterus+, no Clubbing , generalised significant palpable peripheral lymphadenopathy, edema.

Anthropometry:Height : 139.5 cm ( 3- 25 percentile) Weight : 30.6 kg (3- 25 percentile)BMI : 15.77 (10- 25 percentile)

Pale conjuctiva Scleral Icterus Pale oral cavity Multiple pigmented lesions over

legs & knuckles No frontal bossing, dysmorphism No sternal tenderness No evidence of bony deformities or

other vitamin deficiencies SMR : stage 2.

SYSTEMIC EXAMINATION:

Abdomen :soft liver 4cm below RCM , smooth

surface, rounded edges, non-tender, liver span 13 cm.

spleen 1.5 cm below LCM, firm non-tender.

CVS :S1S2 normal, soft systolic

murmur +.RS, CNS – Clinically Normal.

SUMMING UP THE CLUES: 13 yr adolescent girl, 1st born of 3rd degree

consanguineous marriage presenting with - pallor, - icterus, - hyper pigmentation of legs and knuckles,- mild hepatosplenomegaly,- soft systolic murmur with normal birth

weight, uneventful neonatal period, normal development with episodes of pallor and icterus in the past, with no dysmorphic features.

HEMOLYTIC ANAEMIA

INVESTIGATIONS:

Hb : 4.2gRBC : 1.41millionMCV : 105fl (78-98)MCH : 29.8pg (25-35)MCHC: 30.7g/dl (32 – 36)WBC : 2820DC : P30 / L69 / M0.8PLT : 97000

LFTS.bilirubin - Total : 5 mg

Direct : 0.5 mgALK.Phosphatase : 56 u/l(105-

420)Alanine AT : 23 u/l(5-

45)PTT : 15.8INR : 1.33

RETIC COUNT : 3% ESR : 80mm/hr Peripheral smear :

RBCs : Reduced in number, macro-ovalocytes with polychromisia, occasional few microspherocytes.

Platelets : Reduced in number (single and few cells seen).

WBCs : Reduced in number, few Atypical lymphocytes, occasional late normoblast seen (not megaloblast).

No hemoparasite seen.

URINE ROUTINE :Alb - NilSugar - NilBile salt - Nil Bile pigment - NilDep - 1-2 pus cells

STOOL EXM :Occult blood – NegativeNo ova cyst

USG ABDOMEN: Liver :

Uniform texture, no demonstrable focal lesion, portal vein, Hepatic veins, IVC normal , size 14cm.GB - No stonesCBD- Normal, No dilated IHBR.

SPLEEN : 11.6cm Impression: Mild Hepatospleenomegaly,

No Gall stones, No Adenopathy, No free fluid.

OPTHALMOLOGY :No evidence of KF ring, Fundus normal.

SO FAR…

ICTERUS PANCYTOPENIA MILD HEPATOSPLENOMEGALY P-SMEAR SHOWING MACRO-OVALOCYTES,

FEW MICRO SPHEROCYTES, OCCASIONAL LATE NORMOBLAST.

INCREASED RETIC COUNT. BONE MARROW ASPIRATION

PLANNED.

BONE MARROW ASPIRATION:

Erythroid Hyperplasia with reversal of M:E ratio 4:5 There is a small population of late normoblast with

nuclear lobulation – occasional chromatin bridgingA small proportion of early normoblast shows

megaloblastoid changes.There are giant metamyelocyte band forms among

normal granulocytes and their precursor.Lymphoid cells : 5%Blast : <2%

DYSERYTHROPOIESIS WITH MEGALOBLASTIC CHANGES.

---------------- HAM test : Negative.----------------

FURTHER INVESTIGATION:

VIT B12 - 39 pg/ml (211 – 946)

Ceruloplasmin - 41.1 mg/dl (16 – 47) Copper - 124 mcg/dl (80 –

155) FA - 11.8ng/ml (3.1-

17.5) TIBC - 351 (171-

504)

FINAL DIAGNOSIS:

MEGALOBLASTIC ANEMIA WITH PANCYTOPENIA DUE TO VITAMIN B 12 DEFICIENCY.

TREATMENT GIVEN: 1 Unit ‘O’ positive blood transfusion done. Inj. Vit B12 1000mcg im monthly T-FA 5mg 1ODRESPONSE TO THERAPY:

NowHb - 10gTC - 7000Plt - 250000

PERIPHERAL SMEAR:Normochromic Normocytic RBC with occasional macro-ovalocytes.Platelet adequate.WBC adequate & normal in shape.

BROTHER:

Clinically – Pallor, Hyper-pigmentation over knuckles.Hb : 6.2gTC : 8410PLT : 245000Bili- Total : 1.7

- Direct : 1.8Rectic Count : 2.1%Peripheral smear :

RBCs show macrocytesModerate hypochromic with Anisopoikilocytosis changes.WBC - NormalPlt - NormalNo immature cells , No Hemoparasites seen.

ESR - 75mm/hrVIT-B12 - 100.4pg/ml (211-946)FA - 10.74ng/ml (3.1 – 17.5)TIBC - 259 (171 – 504)

TREATMENT:Inj. Vit-B12 - 1000 mcg im monthly.T. FA - 5mg 1OD.

DISCUSSION

VIT – B12 DEFICIENCY CAUSES:

INADEQUATE INTAKE: Strict veg diet.

LACK OF INTRISIC FACTOR: Congenital/Juvenile form.

IMPAIRED ABSORPTION: Regional enteritis, NEC, Ileal resection, Fish tapeworm infestation, Overgrowth of intestinal bacteria, RARELY DEFECT OF THE RECEPTOR FOR IF-B12.

ABSENCE OF VIT-B12 TRANSPORT PROTEIN: TC II Deficiency.

INCREASED DEMAND:Infancy, Pre-maturity.

CLINICAL FEATURES:

Anorexia, Fatiguability, Mental Apathy. Sore Tongue, Papillary Atrophy, Glossitis, Vomitting,

Diarrhoea. Hyperpigmentation of Dorsum of Hands and Knuckles. Hypotonia, Seizures, Developmental Delay. Developmental Regression, Neuro Psychiatric

Changes. Icterus. Pancytopenia.

NEUROLOGICAL FEATURES CAN OCCUR IN THE ABSENCE OF HEMATOLOGICAL FEATURES.

LABORATORY FINDINGS:

Macrocytic Anemia with Prominent Macro-ovalocytosis of RBCs.

Neutrophils may be large and hypersegmented. Pancytopenia can occur in severe cases. Serum methylmalonic Acid and Homocysteine are

elevated. Serum LDH, Bilurubin levels are elevated. Serum Vit-B12 levels are low. Serum Iron and Folic Acid are normal or elevated. Excessive Excretion of methylmalonic Acid in the urine

is reliable and sensitive index of Vit-B12 deficiency.

FURTHER INVESTIGATIONS:

Specific Cause of Vit-B12 deficiency often is apparent from the clinical history.

If there is no obvious cause of Vit-B12 deficiency, Absorption of Vit-B12 can be assessed by the SCHILLING TEST.

TREAMENT:

A Prompt Hematologic response follows parenteral administration of Vit-B12 (1mg) in 2-4 days.

In case of neurological involvement 1mg im daily for at least 2 weeks.

Maintenance therapy is necessary throughout life.

Monthly im injection of 1mg is sufficient.

POINTS OF INTEREST IN OUR CASE…

VIT-B12 DEFICIENCY IN AN ADOLESCENT GIRL TAKING NON -VEGETARIAN DIET.

ICTERUS. PAN CYTOPENIA. HYPER PIGMENTATION. SIBLING ALSO SUFFERING FROM VIT-B12

DEFICIENCY. NO NEUROLOGICAL FEATURES AND

NORMAL DEVELOPMENT.

LITERATURE REVIEW

Pancytopenia due to vit B 12 def in a breast fed infant-

Journal of Pediatric hematology and oncology 2008 vol 25; issue 4(365-367).

A child with vit B 12 def presenting with pancytopenia and hyperpigmentation.

J pediatric hematology and oncology 2004 DEC;26(12):834-60

Imerslund grasbeck syndrome- Indian pediatrics 1999; 36 : 1262-64.

TAKE HOME MESSAGE…

Vit B 12 def can present as hemolytic jaundice.

Pancytopenia in adolescent girl may be vit B 12 def also …

Hyperpigmentation of knuckles can alone be a early manifestation of vit B 12 def…

Vit B 12 def can occur in non-vegetarians TOO.

Parenteral therapy can be used as a diagnostic tool also.

THANK YOU