Reye-like syndrome following treatment with the pantothenic acid antagonist, calcium hopantenate.

Abstract

The patient (case 1) was a 72 year old female with multiinfarct dementia. Four months before our examination she had been started on a regimen of calcium hopantenate therapy (37 mg/kg/&). One day before the examination, with no prodromal symptoms, she developed severe nausea and vomiting, and then became stuporous. On examination her vital signs were as follows: temperature 35 6°C; pulse, 96 beats/min, respiration, 36/min, and BP, 160/70mmHg. She was deeply comatose and unresponsive to noxious stimuli. Pupils were small and reactive to light. Her upper limbs were flaccid and her lower limbs were spastic in flexion, a condition present since the age of 70 years. Deep tendon reflexes were brisk in all four extremities. Hepatosplenomegaly was not observed.Laboratory values at the time of coma included: arterial pH, 704; PaCO2, 12 mmHg; PaO2, 152 mmHg; HC03 , 5 mmol/l; base excess, -22 mmol/l; blood glucose,

Major involvement of Na+‐dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells

“…It has been reported that treatment with the pantothenic acid antagonist calcium hopantenate caused Reye‐like syndrome (Noda et al . ; Shimizu et al . ).…”

“…It is important to clarify whether vitamin transport via SLC5A6 is likely to be inhibited in practice by drugs in the therapeutic range of plasma concentration (nM-lM) to better understand the potential adverse effects in pharmacotherapy. It has been reported that treatment with the pantothenic acid antagonist calcium hopantenate caused Reye-like syndrome (Noda et al 1988;Shimizu et al 1990). Neurometabolic abnormality owing to pantothenic acid deficiency has been considered as one of the causes of this syndrome.…”

“…Treatment with the pantothenic acid antagonist calcium hopantenate causes Reye‐like syndrome, which is an acute metabolic encephalopathy (Noda et al . ). Because biotin and pantothenic acid are not synthesized in the brain, they must be supplied from blood across the BBB to maintain brain homeostasis (Spector and Johanson ).…”

The Coenzyme A Level Modulator Hopantenate (HoPan) Inhibits Phosphopantotenoylcysteine Synthetase Activity

“…Due to its dependence on PanK for metabolic activation, and its competition with Pan for this transformation, HoPan’s effective potency is expected to be highly dependent on the amount of Pan present in the environment. Indeed, the conflicting reports on HoPan’s toxicity in various animals and humans can be reconciled with a knowledge of the circulating levels of Pan in each case, and/or whether Pan was withheld from or added to the diet. ,,, Consequently, contrary to the conclusion of some of these early studies that HoPan induces a Pan deficiency, it is more likely that an underlying Pan deficiency resulted in an apparent increase in HoPan’s potency. One could therefore reasonably conclude that HoPan may be a potent inhibitor under conditions where Pan availability is limited.…”

B Vitamins, Glucoronolactone and the Immune System: Bioavailability, Doses and Efficiency

“…The most dangerous reactions were recorded after treatment with calcium hopantenate, some even fatal [ 78 ]. These included semicoma, Reye-like syndrome, and encephalopathy [ 77 ]. Gastrointestinal disorders and liver dysfunctions have been reported in the elderly [ 78 , 79 ].…”