Severe caffeine intoxication in a preterm neonate

Abstract

Sir: Succinic semialdehyde dehydrogenase (SSADH) deficiency is an inborn error of gamma-aminobutyric acid (GABA) metabolism [3] accompanied by urinary excretion of 4-hydroxybutyric (4-HB) acid, a compound with neuropharmacological properties [5]. Patients present with nonprogressive ataxia, hypotonia, psychomotor retardation, hyperactivity, autistic features and/or convulsions [6]. Jaeken and coworkers [2] reported a successful therapeutic trial with the anticonvulsant Vigabatrin in one patient. In a subsequent report by Gibson et al. [1] Vigabatrin therapy was without clinical improvement in another patient. We wish to report our results of Vigabatrin therapy in SSADH deficiency. Our patient was the second child of consanguineous Turkish parents. She showed gross retardation of motor and psychosocial development, hypotonia and ataxia. Hypotonic cerebral palsy was diagnosed. She sat unsupported at 12 months and walked at 27 months. Gait remained broad based and required support. She did not speak nor comprehend speech, could not feed or dress herself and had no control of bladder and bowel. There was little functional use of the hands. Moreover there were autistic features and severe physical restlessness with insomnia. She indulged in repetitive motor activities, wandering aimlessly for hours during the day and night. She required constant supervision, occasionally with restraint. She developed disruptive and aggressive behaviour with explosive outbursts. At 4 years of age grand mal and myoclonic seizure activity were noted, partially controlled by sodium valproate. At 8 years of age atypical absence seizures developed and ethosuccimide therapy was added. However, seizures could not be completely controlled. At 8 years old SSADH deficiency was diagnosed [4, patient 2]. At 12 years of age Vigabatrin therapy was started with increasing doses fi'om 500 to 3500 mg/d. Within 2 weeks of this therapy there was neurological improvement. There was noticeable improvement in locomotion. Her gait became non-atactic and support was no longer required. Sodium valproate and ethosuccimide therapy was discontinued as seizures resolved. Over the next several weeks there was a modest improvement in mental development. Her IQ improved slightly from < 20 to 20-50. She began to develop speech consisting of about one dozen intelligible words. She fed herself, picked up a cup, drank and managed a spoon, dressed and undressed herself with assistance and showed bladder control during the day. She could execute simple orders and began to imitate domestic duties.

Treatment of Apnea of Prematurity

“…Due to the lack of appropriate quality control, these preparations often provided variable amounts of caffeine from one preparation to other and were a cause of some adverse events. [91,94] The study design for selected trials with caffeine citrate and major outcome measures used to evaluate its efficacy are described in table I. There is only one randomized, placebo-controlled, double-blind study of caffeine in premature infants.…”

“…[88] Toxicity following caffeine overdose manifests as central nervous system irritability, seizure activity, and tachypnea. [89][90][91] Tachycardia was not reported with caffeine overdose. [89] Theophylline appears to have long-term adverse effects.…”

Clinical Pharmacokinetics of Caffeine in Korean Preterm Infants with Apnea of Prematurity

“…Irritability, restlessness, jitteriness, and tachycardia can occur owing to central nervous system (CNS) and cardiovascular stimulation [6][7][8] . An increase in the caffeine levels in the body in creases its potency and toxicity accordingly 9) .…”

Caffeine Citrate

“…term growth and neurological development later in life. [73][74][75][76] Symptoms included tremors, hypertonia, digestive disturbances, cardiovascular failure or tachycardia, jitteriness, irritability, whining and crying. [72] Incidents of caffeine overdose in neonates have been reported in the literature.…”

“…[71] In another nonblind trial, caffeine citrate treatment for up to 32 (mean 23.8) weeks did not adversely influence growth parameters in 28 premature infants. [76] [73][74][75][76] Symptoms included tremors, hypertonia, digestive disturbances, cardiovascular failure or tachycardia, jitteriness, irritability, whining and crying.…”