MEGALOBLASTIC ANEMIA - A CLINICAL SPECTRUM AND A HEMATOLOGICAL PROFILE
Dr. Thomas*, Anand. P**, Dr. Suman Rao***, Dr. Maria Lewin****, Dr. Swarnarekha Bhat*****
St. John's Medical College Hospital, Bangalore.*, St. John's Medical College Hospital, Bangalore.**, St. John's Medical College Hospital, Bangalore.***, St. John's Medical College Hospital, Bangalore.****, St. John's Medical College Hospital, Bangalore.*****
Introduction
Nutritional anemia is a common cause of morbidity in children, iron deficiency anemia being the commonest. However, one has to remember not all nutritional anemias are due to iron deficiency. Megaloblastic anemia due to either VitaminB12 or folate deficiency is one of the causes of nutritional anemia. Megaloblastic anemia has very varied clinical manifestations which can lead to either an undiagnosed or a misdiagnosed anemia. Left untreated it can lead to complications and morbidity including multiple transfusions and its attendant risks. This study aims at identifying the clinical spectrum and the hematological features of this disease.
Materials and Methods
A hospital-based retrospective analysis of case records of all patients admitted and diagnosed as megaloblastic anemia was done. Those with a diagnosis of aplastic anemia were excluded from the study. The study period was from June 2004 - May 2006 and all patients admitted from the age group of 2 months to 18 yrs were included in the study. The data collected was analyzed using SPSS version 10 and a multivariate analysis was done to determine correlation between symptoms, signs and hematological investigations.
Results
21 children with megaloblastic anemia in the above said period was studied. The patient's age ranged from 2 mo-15 years. There was a bimodal distribution with 66.6% of patients being between 2 months-3 years and 33% being in the age group of 13-15 years. There were no patients in age group between 3 years - 13 years. Megaloblastic anemia was more common in female children with the ratio being 1.6:1 in favor of females. The commonest symptoms were pallor (61.9%), fatigue (47.6%) and neurological involvement (33%). The frequency of symptoms and signs are as listed in Tables 1 and 2 respectively.

Table 1: Frequency of Symptoms
Symptoms No of patients (%)
Pallor 13 (61.9%)
Fatigue 10 (47.6%)
Neurological 7 (33%)
Jaundice 5 (23.8%)
Bleeding manifestations 3 (14.3%)
Recurrent fever 2(9.5%)
Weight loss/ failure to gain weight 6(28.6%)


Table 2: Frequency of Signs
Signs No of patients (%)
Wasting/ failure to thrive 13 (61.9%)
Pallor 20 (95.2%)
Skin hyperpigmentation 12 (57.1%)
Hepatomegaly 17(81%)
Neurological signs (apathy/developmental delay/regression/hypotonia) 7 (33.3%)
Splenomegaly 5 (23.8%)


Table 3: Hematological Profile
Investigations Mean ± SD
Hemoglobin (g%) 6.195 ± 2.54
MCV (fl) 98.47 ±10.14
MCH 34.04 ± 4.67
MCHC 34.72 ± 3.31
Corrected reticulocyte count (%) 1.5 ± 2.3
Leukocyte count(/cu mm) 5,880 ± 2904
> Neutrophil count (/cu mm) 1299 ± 922.7
Platelet count /cmm 98,833 ± 56,839


The number of patients who had severe anemia (Hb < 7g%) was 14 (66.6%). The lowest hemoglobin noted was 2.7g%. 2 patients (9.5%) had hemoglobin which was normal but these were patients who had received blood transfusions and 6 patients (28.5%) had MCV which was normal. About 66% of patients had low corrected reticulocyte count.

Pancytopenia was seen in 23.8% of patients. Bicytopenia was seen in 23.8% of the patients. 23.8%of patients had leucopenia. A significant number of patients had neutropenia (66.7%).

Macrocytosis was found in 81% of peripheral smears and bone marrow confirmed Megaloblastic anemia in 92.99%. Vitamin B 12 assay which was done in 8 patients showed low levels (<100pg/ml).

On multivariate analysis neurological involvement correlated significantly with age (P value 0.018%) and symptoms of fatigue (P value 0.012) and fatigue correlated significantly with low Vitamin B12 levels (P value 0.01) and MCHC (P value 0.011).

Resolution of anemia was seen with treatment in 10 patients who subsequently followed up (47.6%). The mean time taken for resolution of anemia was 42.5 days. There was resolution of the neurological signs, most importantly apathy in all the 7 patients who had neurological signs.

Discussion
Megaloblastic anemia is one of the preventable and treatable causes of nutritional anemia. The causes are either Vitamin B12 or folate deficiency or both. The female preponderance as is seen in our study has been seen in another large study done in Zimbabwe by Mukiibi J M et al but this study involved the adults (1). The bimodal nature of the disease can be due to the vulnerability of the age groups. The infants rely on the breast milk of the mother. A child breast fed by a mother who is a Strict vegetarian has a higher risk of developing megaloblastic anemia as has been shown by a study done by Wagnon et al and Sklar etal (2.3)

The other age group in pediatrics which has been seen to be affected is adolescence. The cause for this might lie in the increased intake of junk food and compensatory decrease in the intake of vitamin B12 and folate rich food as has been well illustrated in a study by Suarez et al (4). The neurological involvement was seen in about 7 out of the 21 children (33%). The neurological involvement was mostly apathy, hypotonia and developmental stagnation which was difficult to explain by the degree of anemia. All the cases of neurological involvement were less than 3 years of age. No cases of neurological involvement was seen in adolescents.

Hepatomegaly has been a significant finding in these children. 81% of these children had hepatomegaly and only a small proportion had splenomegaly (23.8%). This finding of hepatomegaly in large proportion of children might be useful in differentiating megaloblastic anemia from aplastic anemia clinically, though it must be stated that lab investigations are necessary for confirmation of diagnosis.

The presence of severe anemia at presentation (Hb< 7 g%) has been seen in 14 of the 21 patients (66%).
Conclusion
Megaloblastic anemia is one of the common causes of undiagnosed anemia and the treatment is simple and easily affordable. If left untreated it can lead to morbidity both because of anemia and attendant neurological involvement.

The commonest manifestations in Megaloblastic anemia include a triad of pallor, hyperpigmented skin and neurological involvement.

Neutropenia is a common concomitant finding in Megaloblastic anemia and can be associated with leucopenia in a small number of patients. A correct diagnosis and prompt therapy leads to a complete and un eventful recovery.
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