Answer to Hypotonia: A Simple Hemogram

Güler Kanra, MD; Mualla Cetin, MD; Sule Unal, MD; Goknur Haliloglu, MD; Tulay Akça, MD; Nejat Akalan, MD; Ates Kara, MD


J Child Neurol. 2005;20(11):930-931. 

A 1-year-old boy with weight loss, decreased activity, and psychomotor regression is presented. He was subjected to an extremely detailed evaluation, including electroencephalography (EEG) and magnetic resonance imaging (MRI), until a simple hemogram in our center revealed that he had macrocytic anemia with megaloblastic changes in the bone marrow. His history revealed that he had been exclusively breast-fed by his vegetarian mother. Further investigations showed low serum vitamin B12 concentration, methyl-malonic aciduria, and homocysteinemia, indicating that the macrocytic anemia was due to vitamin B12 deficiency. This boy represents a case of macrocytic anemia and hypotonia owing to vitamin B12 deficiency that developed because of exclusive breast-feeding by a vegetarian mother.

Vitamin B12 is found primarily in meat, fish, and dairy products, and the daily vitamin B12 requirements for children and adolescents range from 0.4 to 2.4 µg.[1] Vitamin B12 is necessary for the production of methylenetetrahydrofolate, which is essential for DNA synthesis. Deficiency of vitamin B12 leads to delayed DNA synthesis in the rapidly growing hematopoietic cells, and this can result in macrocytic anemia,[2] hypersegmentation of neutrophils, leukopenia, thrombocytopenia, and pancytopenia. Accompanying neurologic abnormalities of this complex syndrome include paresthesias, sensory deficits, loss of deep tendon reflexes, movement disorders, developmental regression, dementia, and neuropsychiatric changes.[3,4,5,6] Brain atrophy and delayed myelination can be observed in a magnetic resonance imaging (MRI) study. Failure to thrive, irritability, anorexia, vomiting, diarrhea, and jaundice are other common complaints of these patients. Possible causes of vitamin B12 deficiency in childhood include decreased intake, abnormal absorption, and defects in vitamin B12 transport and metabolism. Most frequently, it is observed in exclusively breast-fed infants of strictly vegetarian mothers.[4,7,8,9] Failure to associate the neurologic findings with vitamin B12 deficiency can result in unnecessary investigations. To emphasize this association, we report an infant who developed vitamin B12 deficiency following exclusive breast-feeding by a strict vegetarian mother.

A 1-year-old boy presented with weight loss, decreased activity, weakness, psychomotor retardation, and anemia. He was the second child of a non-consanguineous marriage. He was born following an uneventful pregnancy with a birthweight of 3250 g. He had been exclusively breast-fed without any supplementation until admission to the hospital.

His history showed that his physical and psychomotor development was normal, with a spontaneous smile at 2 months and supported sitting at 6 months, until he ceased to gain weight, gradually lost social interaction, and became unable to sit or roll over.

On admission, his weight was 9.5 kg (3rd-10th percentile), length was 76 cm (25th-50th percentile), and head circumference was 49 cm (> 90th percentile). Physical examination revealed a pale, apathic, and hypotonic boy with poor head control. Deep tendon reflexes were hyperactive in all extremities.

A previously obtained electroencephalogram showed baseline rhythm irregularities and decreased bioelectrical activity. A cranial MRI study showed minimal atrophy and fluid collection in the right frontal and left frontotemporal hemispheres. Analysis of amino acids in the urine and blood was normal. In our center, the hemoglobin was 5 g/dL, white blood cell count was 4.8 × 109/L, mean corpuscular volume was 104 fl, platelets were 85 × 109/L, and absolute neutrophil count was 846/µL. The mother's hemoglobin was 12.2 g/dL, white blood cell count was 8.7 109/L, mean corpuscular volume was 84 fl, and platelets were 299 × 109/L. The total serum bilirubin (for the patient) was 3.3 mg/dL, direct serum bilirubin was 0.5 mg/dL, aspartate aminotransferase was 32 IU/L, and alanine aminotransferase was 62 IU/L. The bone marrow aspiration exhibited megaloblastic changes in both myeloid and erythroid series. Serum vitamin B12 was 128 ng/L (normal range160-900). The mother's vitamin B12 level was 245 ng/L. Both the mother's and the patient's folic acid levels were normal. The plasma homocysteine level was > 50 µmol/L (normal range 5-15), and urine organic acid analysis revealed a high urinary methylmalonic acid level.

A detailed history revealed that the mother had been a vegetarian for the last 15 years. A diagnosis of vitamin B12 deficiency was entertained, and treatment with 100 g intramuscular cyanocobalamin was promptly pursued.

With the increased popularity of vegetarian diets, a new etiology has emerged for vitamin B12 deficiency in infants: poor intake from a breast-feeding vegetarian mother.

The vitamin B12 levels in breast milk parallel those in the serum.10 Normally, a newborn has 25 µg vitamin B12 content in the liver, an amount predicted to be sufficient until the end of the first year of life, even with low intake.11 Vitamin B12 deficiency can cause irreversible neurologic damage in infancy, and this effect is more prominent in infants who have been exposed to deficiency during the intrauterine period. Brain atrophy, microcephaly, and myoclonic seizure disorder are among the most commonly observed neurologic sequelae. In our patient, cranial MRI revealed minimal atrophy and fluid collection in the right frontal and left frontotemporal hemispheres. Although brain atrophy is an expected finding in patients with vitamin B12 deficiency, fluid collection in the described areas is a new finding.

In our patient, 3 days after the onset of vitamin B12 treatment, the patient exhibited tremors and fasciculations in the tongue and extremities, and these findings disappeared with clonazepam in a few days. The cause of involuntary movements that can appear rarely after treatment in infantile cobalamin deficiency is not known.

The infants of vegetarian mothers have an increased risk of permanent brain injury caused by vitamin B12 deficiency. In a case with hypotonia and developmental delay, the physician must obtain a detailed history, including the diet, as well as be alert regarding the routine laboratory tests, such as a hemogram, before thinking about extereme diagnoses and laboratory work-up. In our case, anemia, high mean corpuscular volume value, and mild, indirect hyperbilirubinemia pointed to a diagnosis of hypotonia and neurodevelopmental regression, which was retrospectively confirmed by the maternal history and laboratory data. Vitamin B12 deficiency must be considered in the differential diagnosis of a hypotonic infant.

CLICK HERE for subscription information about this journal.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.