Infantile Tremor Syndrome after Peroral and Intramuscular Vitamin B12 Therapy: Two Cases

Introduction

Deficiency of vitamin B12, with an essential role in cellular metabolism, is commonly observed in Turkey (Koc A et al., Eur J Nutr 2006; 45: 291–297). The most common cause of vitamin B12 deficiency is insufficient intake of the vitamin in diet. Due to strict vegan diets or pernicious anemia, it is observed among breastfed infants of mothers with low vitamin B12 levels. Mothers are generally asymptomatic. The affected infants continue to have healthy development for the first 6 months due to available hepatic stocks, but if deficiency continues irritability, nutritional problems, weakness, lethargy and neurodevelopmental regression may be observed. Infections generally trigger involuntary movements like tremor and rarely paradoxical intramuscular (IM) B12 vitamin treatment may cause tremor. However, infantile tremor is not reported after peroral (PO) treatment. We wish to share two cases developing infantile tremor after PO and IM vitamin B12 treatment.

Case 1

A 21-month old male patient, with parents distantly related, attended our hospital with unintentional movements beginning 12 h previously. Assessment at the first center attended considered the patient was having a seizure and intravenous diazepam was administered, then phenytoin loading was administered. However, there was no improvement in movements. One week before that the patient had attended the same external center and been tested due to motor development regression. The patient was born by the normal route at term weighing 3100 g with no complications. Unsupported sitting began at 15 months, but he still could not walk. Examination of the patient found normal consciousness; however, he appeared restless. Head circumference was 47 cm (10p), body weight 11 kg (25p) and height was 84 cm (25p). Hair was thin, skin had mild hyperpigmentation especially in joint regions. The patient was generally hypotonic, and he could not hold his head up or sit. Clear tremor was observed especially of the head and upper extremities. When he calmed down and slept, the tremor stopped completely. With deeper history, the family’s socioeconomic level was low, the patient was only fed with breastmilk and had macrocytic anemia diagnosis due to vitamin B12 deficiency placed 1 week previous. Tests from that time identified hemoglobin 8.1 g/dL, hematocrit 27.8%, MCV 87 fL, iron 32 ug/dL (65–120), and vitamin b12 level 12.8 pg/mL (247–1170). For this, he had drunk half of a 1000 mcg/ml cyanocobalamin ampoule prepared for IM administration. On admission to our hospital, hemoglobin was 7.9 g/dL, hematocrit 26%, MCV 86 fL, ferritin 3.5 ng/mL (65–120), folic acid 11.9 ng/mL, homocysteine 31 µmol/L (<8) and vitamin B12 level was 831 pg/mL. Urine organic acid assessment observed trace amounts of methylmalonic acid excretion. Peripheral distribution observed macrocytic hypochromic oval erythrocytes, anisocytosis, poikilocytosis and hypersegmentation of neutrophils.

Cranial tomography found cerebral atrophy ([Fig. 1]). Electroencephalography found no epileptic discharge, but only background rhythm slowing ([Fig. 2]). The results of clinical and laboratory assessment of the patient diagnosed infantile tremor linked to iron deficiency-B12 vitamin deficiency and 100 µgr/g B12 treatment intramuscular and 0.1 mg/kg/day clonazepam PO was begun. Additionally, PO iron treatment was begun for iron deficiency. Nutrition was organized. Assessment of the mother identified vitamin B12 deficiency (B12: 134 pg/dL). Treatment began for the mother. Follow-up MR images found clear cerebral atrophy ([Fig. 3]). On the 15^th day of treatment, the patient’s tremor clearly reduced and the patient could sit unsupported. His interest in his surroundings clearly increased. EEG taken one week later found encephalopathy had regressed ([Fig. 4]). Four weeks later the patient’s tremor had fully stopped. Clonazepam treatment was reduced and stopped. Laboratory tests were performed again with hemoglobin 12.4 g/dL, hematocrit 38.7%, MCV 80 fL, ferritin 18 ng/mL, and vitamin B12 level 1914 pg/mL. Continuing monthly B12 treatment, the patient was followed. During 3^rd month check-up, he began to take steps while supported.

Fig. 1 Cranial tomography.

Fig. 2 Electroencephalography.

Fig. 3 T1Weighted and T2Weighted axial Magnetic Resonance Images.

Fig. 4 Electroencephalography.

Case 2

A 10-month old male patient attended with shaking which began one day previously. Shaking, which disappeared during sleep, was present in the whole body but more pronounced in the hands. The patient was followed by pediatric hematology due to vitamin B12 deficiency and had been receiving 100 µgr/day IM vitamin B12 for 3 days. Before treatment the patient had hemoglobin 9.8 g/dL, hematocrit 28.2%, MCV 106 fL, iron 97 ug/dL (65–120), folic acid 20 ug/L (3.1–17.5) and vitamin B12 level 57.3 pg/mL (247–1170). Macrocytosis, anisocytosis and poikilocytosis were identified with peripheral spread. The patient was born by normal vaginal birth at 3350 g. Additional feeding began at eight months, but he was generally breastfed. Examination found head circumference 45 cm (25 p), height 74 cm (50 p) and weight 9 kg (25–50 p). He had full head control but could not sit unsupported and had reduced interest in his surroundings. There was no clear hyperpigmentation. Urine was not studied for organic acid and homocysteine levels. Cranial MRI observed mild cerebral atrophy. EEG was normal. The patient was begun on 0.1 mg/kg/day clonazepam in addition to 100 µgr/day B12 treatment. Follow-up 1 week later found he had improved, and the tremor regressed. Clonazepam treatment was reduced and stopped after full loss of tremor at 1-month follow-up. At his 1-year check-up, the patient could sit fully supported and had begun to take steps with aid. Blood tests found hemoglobin was 12.5 g/dL, hematocrit 35.3%, MCV 79 fL, folic acid 3.5 ug/L (3,1–17,5) and vitamin B12 level 1686 pg/mL (247–1170).