9 April 2008
AN UNUSUAL PRESENTATION OF ANAEMIA: A REPORT OF THREE CASES
The present communication is intended to report on three siblings of a family who presented with an unusual sign of anaemia related to vitamin B-12 deficiency. The chief complaints were a peculiar hyperpigmentation of the hands and feet especially over the knuckles and recurrent bouts of vomiting for a prolonged period. The changes reversed promptly on vitamin B-12 administration.
Three siblings of the same family presented with symptoms of lethargy, easy fatigability, palpitation and deteriorating school performance. They also had repeated vomiting and loose motion along with hyperpigmentation of fingers (especially knuckles) (Fig. 1) and toes (especially great toe knuckles) and oral ulcers. They were strictly vegetarians belonging to a low socio-economic family. The clinico-laboratory profile of the cases is shown in Table 1. The examination of stool for ova, parasite and cyst, and the culture of the same were non-contributory. The stool for occult blood was negative. The liver function and the renal function tests were normal.
|Features||Case 1||Case 2||Case 3|
|Age and sex||9 years; female||7 years; female||4 years; male|
|Presenting complaints||Vomiting and loose stools – 5 years||Vomiting and loose stools – 4 years||Failure to thrive – 2 years|
|Hyperpigmentation especially over knuckles – 2 years||Hyperpigmentation especially over knuckles – 3 years||Hyperpigmentation especially over knuckles – 3 years|
|Clinical findings||Severe pallor||Severe pallor||Severe pallor|
|Mild icterus||Mild icterus||Mild icterus|
|Smooth shiny tongue||Smooth shiny red tongue||Onychodystrophy|
|Hyperpigmented spots over tongue||Oral ulcers||Fine sparse hypopigmented hairs|
|Oral ulcers||Fine sparse hypopigmented hairs||Knuckle hyperpigmentation|
|Stomatitis, glossitis||Knuckle hyperpigmentation||Hepatosplenomegaly|
|Fine sparse hypopigmented hairs||–||–|
|Haematology (at admission)||TLC – 3500/mm3 (N – 53, L44)||TLC – 4200/mm3 (N – 46, L – 52)||TLC – 3800/mm3 (N – 36, L – 62)|
|Platelets – 32 000/mm3||Platelets – 49 000/mm3||Platelets – 75 000/mm3|
|Reticulocyte – 1.4%||Reticulocyte – 2.1%||Reticulocyte – 1.6%|
|RBC – 1.8 million/mm3||RBC – 2.2 million/mm3||RBC – 1.9 million/mm3|
|Haemoglobin – 3.6 g%||Haemoglobin – 5.4 g%||Haemoglobin – 4.2 g%|
|PCV – 32%||PCV – 36%||PCV – 28%|
|MCV – 104 fL||MCV – 102 fL||MCV – 108 fL|
|MCHC – 29.68%||MCHC – 32.74%||MCHC – 28.46%|
|MCH – 25 pg||MCH – 28 pg||MCH – 22 pg|
|ESR – 56 mm 1st h||ESR – 32 mm 1st h||ESR – 24 mm 1st h|
|Serum bilirubin – 4.3 (UC – 3.5; C – 0.8)||Serum bilirubin – 3.9 (UC – 3; C – 0.9)||Serum bilirubin – 3.2 (UC – 2.8; C – 0.4)|
|Serum vitamin B 12 level||98 pg/mL||132 pg/mL||72 pg/mL|
|(Normal: 211–911 pg/mL)||(Normal: 211–911 pg/mL)||(Normal: 211–911 pg/mL)|
|Haematology (after treatment)||TLC – 8200/mm3 (N – 48, L – 48)||TLC – 8300/mm3 (N – 46, L – 42)||TLC – 5400/mm3 (N – 52, L – 44)|
|Platelets – 162 000/mm3||Platelets – 226 000/mm3||Platelets – 196 000/mm3|
|Reticulocyte – 3.4%||Reticulocyte – 2.8%||Reticulocyte – 3.8%|
|RBC – 3.6 million/mm3||RBC – 5.4 million/mm3||RBC – 4.2 million/mm3|
|Haemoglobin – 8.4%||Haemoglobin – 9.2%||Haemoglobin – 10.6%|
|MCV – 92 fL||MCV – 88 fL||MCV – 90 fL|
All three children had macrocytic red cell indices.
The bone marrow aspiration was compatible with megaloblastic changes. The Hepatitis B and Hepatitis C virus serology were normal. The serum vitamin B-12 values in the first, second and the third child were 98 pg/mL, 132 pg/mL and 72 pg/mL, respectively (reference range: 211–911 pg/mL). The serum folate was normal. Based upon the above findings, nutritional vitamin B-12 deficiency anaemia was diagnosed. All the children were treated with intramuscular vitamin B-12 injections along with oral iron, folic acid, multi-vitamins and nutritious diet. There was marked subjective improvement in the children. The well-being returned and the pallor disappeared. They were discharged home with proper dietary advice. At the end of 1 month, hyperpigmentation at the sites mentioned above had decreased drastically in all three children.
The most common cause of vitamin B-12 deficiency anaemia in today's world in the developed countries is its specific malabsorption.1 Florid, symptomatic anaemia is far less common than subclinical deficiency. The clinical features of cobalamin deficiency involve primarily the blood, the gastrointestinal tract and the central nervous system.2
It may be observed in deficient intake of vitamin B-12 as with vegans-strict vegetarians who avoid all dairy products as well as meat and fish.3
The common causes impairing its absorption from the small intestines include gastric surgery, pernicious anaemia, inflammatory conditions such as regional enteritis, intestinal bacterial overgrowth and Diphyllobothrium latum infestation of the gut. Rare causes include defects/absence of intrinsic factor-B12 receptor in the terminal ileum, Imerslund–Gräsbeck syndrome and Transcobalamin II deficiency.
The symptoms of vitamin B-12 deficiency are non-specific. Commonly reported ones are weakness, fatigue, failure to thrive, irritability, glossitis, vomiting, diarrhoea and icterus.
Neurological symptoms seen commonly are parasthesias, sensory deficits, hypotonia, seizures, developmental delay, developmental regression and neuropsychiatric changes.
The neurological changes may either occur in isolation or may precede the haematological abnormalities.4
Hyperpigmentation in vitamin B-12 deficiency is reported infrequently. It may be observed in any age group. Simsek et al.5 described it in a 16-month-old infant while Lee et al.6 observed it in a 65-year-old individual.
Many pathogenetic mechanisms have been put forward to explain the hyperpigmentation. The literature was reviewed extensively by Marks et al.7 Mori et al.,8 on the basis of electron microscopic findings, concluded that the dominant mechanism of hyperpigmentation was not a defect in melanin transport but an increase in melanin synthesis. The hyperpigmentation resolves completely upon administration of vitamin B-12 supplementation.5–10 This is in contrast to the hyperpigmentation observed in Imerslund–Gräsbeck syndrome, in which it is irreversible.11
In conclusion, vitamin B-12 deficiency should be considered in the differential diagnosis of a child presenting with hyperpigmentation and macrocytic red cell indices.