Outbreak of Life-Threatening Thiamine Deficiency in Infants in Israel Caused by a Defective Soy-Based Formula

Abstract

ABSTRACT. Objective. Between October and November 2003, several infants with encephalopathy were hospitalized in pediatric intensive care units in Israel. Two died of cardiomyopathy. Analysis of the accumulated data showed that all had been fed the same brand of soy-based formula (Remedia Super Soya 1), specifically manufactured for the Israeli market. The source was identified on November 6, 2003, when a 5.5-month-old infant was admitted to Sourasky Medical Center with upbeat nystagmus, ophthalmoplegia, and vomiting. Wernicke's encephalopathy was suspected, and treatment with supplementary thiamine was started. His condition improved within hours. Detailed history revealed that the infant was being fed the same formula, raising suspicions that it was deficient in thiamine. The formula was tested by the Israeli public health authorities, and the thiamine level was found to be undetectable (<0.5 g/g). The product was pulled from the shelves, and the public was alerted. Thiamine deficiency in infants is very rare in developed countries. The aim of this study was to report the epidemiology of the outbreak and to describe the diagnosis, clinical course, and outcome of 9 affected infants in our care.Methods. After the index case, an additional 8 infants were identified in our centers by medical history, physical examination, and laboratory testing. The group consisted of 6 male and 3 female infants aged 2 to 12 months. All were assessed with the erythrocyte transketolase activity assay, wherein the extent of thiamine deficiency is expressed in percentage stimulation compared with baseline (thiamine pyrophosphate effect [TPPE]). Normal values range from 0% to 15%; a value of 15% to 25% indicates thiamine deficiency, and >25% indicates severe deficiency. Blood lactate levels (normal: 0.5-2 mmol/L) were measured in 6 infants, cerebrospinal fluid lactate in 2 (normal: 0.5-2 mmol/L), and blood pyruvate in 4 (normal: 0.03-0.08 mmol/L). The diagnostic criteria for thiamine deficiency were abnormal transketolase activity and/or unexplained lactic acidosis. Treatment consisted of intramuscular thiamine 50 mg/day for 14 days combined with a switch to another infant formula.Results. Early symptoms were nonspecific and included mainly vomiting (n ‫؍‬ 8), lethargy (n ‫؍‬ 7), irritability (n ‫؍‬ 5), abdominal distension (n ‫؍‬ 4), diarrhea (n ‫؍‬ 4), respiratory symptoms (n ‫؍‬ 4), developmental delay (n ‫؍‬ 3), and failure to thrive (n ‫؍‬ 2). Infection was found in all cases. Six infants were admitted with fever. One patient had clinical dysentery and group C Salmonella sepsis; the others had mild infection: acute gastroenteritis (n ‫؍‬ 2); upper respiratory infection (n ‫؍‬ 2); and bronchopneumonia, acute bronchitis, and viral infection (n ‫؍‬ 1 each). Two infants were treated with antibiotics. Three infants had neurologic symptoms of ophthalmoplegia with bilateral abduction deficit with or without upbeat nystagmus. All 3 had blood lactic acidosis, and 2 had high cerebrospinal fluid lactate levels. Patient 1, our index case, wa...

Lack of severe long-term outcomes of acute, subclinical B1 deficiency in 216 children in Israel exposed in early infancy

“…Outcomes of children affected by the B 1 -deficient diet in Israel have been reported in several studies (22)(23)(24)(25). Fattal-Valevski et al (22).…”

“…Fattal-Valevski et al (22). described nine children hospitalized in their medical center because of severe thiamine deficiency; most of them had severe gastrointestinal symptoms, failure to thrive, and behavioral and neurological changes, including ophthalmoplegia and nystagmus in three cases.…”

“…The cause was found to be a soy-based infant formula (manufactured by Humana, (Herford, Germany) for distribution in Israel as Remedia) lacking vitamin B 1 due to a change in May 2003 in the formula composition (21,22). The deficient formula was apparently sold in Israel for about 6 mo, from May 2003 to 7 November 2003, when the diagnosis of beriberi was established.…”

Infant Botulism: Is There an Association With Thiamine Deficiency?

“…3 Unfortunately, the blood sample for determination of the pretreatment thiamine level was lost on transport. To our surprise, the boy showed signs of recovery, such as movements of his upper limbs, 24 hours after the first thiamine dose.…”

“…Therefore, infant botulism and thiamine deficiency may cause very similar neurologic symptoms in infants. [3][4][5][6][7] Of the 8 BoNT serotypes A through H, only serotypes A, B, E, F, and H cause human disease. There are 3 types of botulism: (1) the classic intoxication in food-borne botulism and (2) wound and (3) infant botulism.…”