Child's Nervous System

, 25:1477

Infantile encephalopathy due to vitamin deficiency in industrial countries


  • Ibrahim Abu-Kishk
    • Pediatric Intensive Care UnitAssaf Harofeh Medical Center
    • The Sackler Faculty of MedicineTel-Aviv University
  • Marianna Rachmiel
    • Pediatric Intensive Care UnitAssaf Harofeh Medical Center
    • The Sackler Faculty of MedicineTel-Aviv University
  • Chen Hoffmann
    • The Sackler Faculty of MedicineTel-Aviv University
    • Department of ImagingChaim Sheba Medical Center
  • Eli Lahat
    • The Sackler Faculty of MedicineTel-Aviv University
    • Pediatric Neurology UnitAssaf Harofeh Medical Center
    • Pediatric Intensive Care UnitAssaf Harofeh Medical Center
    • The Sackler Faculty of MedicineTel-Aviv University
Original Paper

DOI: 10.1007/s00381-009-0942-3

Cite this article as:
Abu-Kishk, I., Rachmiel, M., Hoffmann, C. et al. Childs Nerv Syst (2009) 25: 1477. doi:10.1007/s00381-009-0942-3



Severe avitaminosis causing life-threatening conditions in the infantile age group is extremely uncommon and has been reported in babies with malabsorption receiving prolonged inadequate vitamin supplements.

Case reports

We report two infants who presented with neurological deterioration. Immediate work-up and treatment for infectious and inborn metabolic disorders were initiated and the diagnosis, made with a few days delay, was prolonged avitaminosis of thiamine (B1) and cobalamin (B12). B1 deficiency was suspected when further neurological deterioration was observed during administration of intravenous fluids containing glucose in an infant with high lactate levels in the cerebrospinal fluid. High transketolase activity that normalized after thiamine treatment and the findings in the MRI and MRS of the brain confirmed the suspected diagnosis. B12 deficiency was suspected in an infant of a strict vegetarian mother who presented with neurological deterioration and severe megaloblastic anemia. The diagnosis was confirmed when low serum levels of B12 and methylmalonic aciduria were detected and treatment with B12 resulted in normalization of urinary methymalonic acid.


Avitaminosis, even in industrialized countries, should be considered in an atypical age group with no known risk factors. Early diagnosis and prompt treatment may accomplish a quick recovery with fewer sequelae.


Wernicke's encephalopathyThiamine deficiencyCobalamin deficiencyAvitaminosis


Severe avitaminosis causing life-threatening conditions in the infantile age group is extremely uncommon and has been reported in babies with malabsorption receiving prolonged inadequate vitamin supplements [1].

The active ester form of vitamin B1, thiamin pyrophosphate, acts as a coenzyme in carbohydrate metabolism through the decarboxylation of alpha-keto acids, and plays a role in the formation of three essential enzyme complexes: pyruvate dehydrogenase complex, alpha-ketoglutarate complex, and transketolase. Thiamine deficiency causes two known syndromes: (1) Beriberi disease, presenting as a neurologic, gastroenterologic, and cardiologic disorder; and (2) Wernicke's encephalopathy (WE), characterized by the triad of ophthalmoplegia, ataxia, and consciousness disturbance [2]. WE has been described mainly among alcoholic or malnourished patients, or in those treated with prolonged parenteral nutrition. Pediatric WE is under-diagnosed, most probably since most patients do not exhibit all three classic signs [2, 3]. WE in infancy is very rare, and has been observed in breast fed infants of mothers who have an inadequate intake of thiamine. It was recently reported in infants fed by thiamine-deficient soy-based infant formula [4].

The active form of cobalamin (B12), deoxyadenosylcobalamin, is essential for hydrogen shifts, which play a role in DNA synthesis and amino-acid metabolism. B12 deficiency may imitate methylmalonic aciduria and homocystinemia [5], which result in neurologic abnormalities including mental retardation, ataxia, pyramidal deficit, seizures, and degeneration of the spinal cord, and megaloblastic anemia [6]. Cobalamin deficiency in pregnant and breast-feeding women and their babies has been found in different regions of the world, due to a poor diet low in animal products, and intestinal parasitic infections [68].

We hereby present two previously healthy infants who were hospitalized due to acute neurological deterioration and seizures. Vitamin B1 (thiamine) and vitamin B12 (cobalamin) serum concentrations were deficient due to insufficient dietary supply.

Case reports

Case 1

A previously healthy, 5.5-month-old female, was admitted due to sleepiness, irritability, and loss of eye contact. Possible exposure to drugs or poison was negative. The baby had been fed exclusively on a soy infant formula for the last 5 months.

On examination, she weighed 6,620 g, had roving-glazed eyes with no eye contact, flaccid limbs, and diminished tendon reflexes. No primitive reflexes were found. Vital signs were normal and there was no hepatosplenomegaly.

Complete serum blood counts were normal with elevated lactate levels of 5.86 mmol/L (normal range = 1.1–2.3 mmol/L) and pyruvate levels of 1.4 mg/dl (normal range = 0–1 mg/dl). Other amino-acid levels in blood and organic acids in urine were within the normal range.

A lumbar puncture revealed high lactate levels 6.6 mmol/L. Blood cultures, enterovirus polymerase chain reaction (PCR), Herpes virus PCR and West Nile Fever serology were all negative. Antibiotic and antiherpetic treatment was initiated. A cranial computed tomography (CT) scan revealed no pathological findings. Electroencephalogram (EEG) showed no specific findings except for intermittent diffuse deceleration. Maintenance intravenous fluid containing 5% dextrose and 0.45% sodium chloride was started immediately. A few hours later, she became stuporous with short apneic episodes: mechanical ventilation was initiated. Enteral thiamine 500 mg/day, vitamin C 500 mg/day, vitamin E 1,000 mg/day, riboflavin 120 mg/day, carnitine 600 mg/day, and coenzyme Q 32 mg/day were initiated. Brain magnetic resonance imaging (MRI; Fig. 1) and magnetic resonance spectroscopy (MRS; Fig. 2) revealed bilateral hyperintense lesions in T2-weighted images affecting the putamen, anterior thalamus, periaqueductal, and posterior parts of the brainstem. A high lactate excretion was detected at the brainstem area. The MRI findings were compatible with Leigh's disease or thiamine deficiency. Muscle biopsy revealed no specific findings. Mitochondrial respiratory chain enzyme levels were normal after adding vitamins to the specimen. One day after initiation of the vitamins, the baby began to improve and was extubated within 2 days. On day 7, thiamine was administered parenterally, 50 mg/day, due to high transketolase activity [17.65% (normal range = 0–15%)], which is influenced by serum thiamine levels. Other supplemental vitamins were stopped. After 3 weeks of thiamine treatment, transketolase activity was within the normal range, 4.4%.
Fig. 1

T2 coronal slice (MRI) at the level of the midbrain demonstrated hyperintense signals in the periaqueductal area
Fig. 2

MRS of the abnormal periaqueductal area using TE of 144 ms showed a lactate peak

An epidemiological study discovered that due to a manufacturing error, the imported soy infant formula did not contain thiamine at all [4]. A month later, MRI and MRS demonstrated improvement and no lactate surge at the brainstem and periaqueductal areas, but there were still hyperintense lesions in the putamen and subcortical white matter of both frontal lobes. At the age of 8 months, convulsive episodes were observed and antiepileptic treatment was initiated. At the age of 1 year, the baby still had delayed motor milestone achievements, external ophthalmoplegia, mild hypotonia, and decreased muscle reflexes.

Case 2

A 7-month-old female infant was admitted due to an atonic convulsive episode and lethargy with a febrile upper respiratory tract infection. She was breast-fed exclusively until admission; the baby’s mother was a strict vegetarian. Past history was normal until the age of 4 months, after which she had a sad appearance, became irritable, and regression of motor and cognitive development was noticed. She weighed 5,000 g, was malnourished, very pale, lethargic, and had hypotonia with normal tendon reflexes. Heart sounds were normal, pulse rate was 160/min, she was dyspneic, and respiratory rate was 58/min with crackles heard over the left lung. Blood glucose was 10 mg% (normal range = 60-110 mg%), which was immediately reversed by glucose bolus. Electrolyte serum concentrations were normal, and liver enzymes were mildly elevated (AST 288 U/L, ALT 59 U/L; normal range, 5–87 U/L, 4–52 U/L, respectively). Complete blood count revealed thrombocytopenia of 29,000/mm3 and megaloblastic anemia with Hgb 3.8 g/dl, MCV 98 µm3, and MCHC 33.3 gHb/dl. Vitamin B12 serum level was 77 pg/ml (normal = 200–950 pg/ml), urine methylmalonic acid was 6,815 mmol/mol creatinine (normal <40 mmol/mol creatinine) and serum homocysteine level was 71.6 mmol/L (normal range = 5–20 mmol/L). Maternal vitamin B12 serum level was 150 pg/ml. Lobar pneumonia was found on chest X-ray. EEG and brain-stem-evoked response audiometry were both normal. She was treated with intravenous fluids, blood products, ceftriaxone, high-dose vitamin B12 (1,000 μg/d) and folic acid (5 mg/day). Rapid cardiovascular, respiratory, and hematological improvement was noticed. Subsequently, normal methylmalonic acid and homocysteine levels were detected. However, the neurological recovery was incomplete—she remained hypotonic with reduced spontaneous movements. By the age of 1 year, she demonstrated normal social interaction, but delayed milestone achievements and hypotonia with normal tendon reflexes.


Two babies suffering neurological deterioration due to severe vitamin deficiency were presented. The diagnosis of WE in the first case presented was clinically suspected due to the roving eyes, lactic acidosis, and further deterioration after infusion of fluids containing glucose [9, 10]. CT scan of the brain was inconclusive and did not help in confirming the diagnosis. However, the MRI and MRS findings were pathognomonic [11, 12]. Thiamine was initiated even before receiving the laboratory results. Later on, an epidemiological survey discovered that the imported soy infant formula, which the baby received, did not contain any thiamine at all. At that time, neurological improvement had already been noticed. The onset of neurological symptoms in cases of a thiamine-deficient diet in children varies from 23 days to 6 months [3]. The MRI hyperintense areas may disappear completely after 1 month of treatment in children with a thiamine-deficient diet of relatively short duration (1 to 2 months) [12]. The infant presented by us had a thiamine-deficient diet for a prolonged period of 5 months, and although she received thiamine early on in the course her hospitalization, MRI imaging did not reveal a complete recovery after 1 month of thiamine treatment and neurological improvement was incomplete. This probably indicates that 5 months on a strict thiamine deficient diet is a long period for infants and may cause irreversible insult to the brain.

Dietary cobalamin deficiency causing neurological and hematological symptoms is very rare in infancy and may causes death in unrecognized and untreated babies [6, 13]. Exclusively breast-fed infants of vegetarian mothers are in danger of suffering from a cobalamin-deficient state. Supplementation of B12 to vegetarian women during pregnancy and lactation is a World Health Organization recommendation [5], one that was not fulfilled in this case.


We consider it important to increase awareness of avitaminosis in infancy. This may occur even in industrialized populations. Cases presenting with encephalopathy, neurological developmental regression, hematological disorders, and further deterioration after intravenous glucose loads, which may aggravate their symptoms, are highly suspicious. Thiamine must be started immediately, since complete investigation and complete diagnosis is time-consuming. Adding vitamin B1 to the treatment in the meantime will cause no harm, but may alter the final outcome. We also suggest promoting a consultation meeting between every new breast-feeding mother and her physician for the initiation of vitamin B12 supplements in cases of a strict maternal vegetarian diet.

Copyright information

© Springer-Verlag 2009