Case Presentation: A 26-day-old girl born full term was transferred to our hospital due to persistent feeding intolerance, acute respiratory failure and hypotonia of unclear etiology. She initially presented at day-of-life (DOL) 19 with 4 days of worsening feeding difficulty, increasing lethargy, and new dyspnea. She had normal stools and no unusual exposures. CPAP support and tube feeding were required. She received 5 days of empiric antibiotics, but septic work-up was negative. She was rhino/enterovirus positive. Vital signs were significant for hypertension, tachycardia, and respiratory support with CPAP (21% FiO2). She was non-toxic, without dysmorphic features, but showed ptosis bilaterally. Pupils were equal, round, and sluggishly reactive. She had diffuse hypotonia (more notable axially) with positive scarf sign bilaterally, decreased passive resistance, and poor tone on horizontal suspension. No focal deficits. Moro and suck reflexes were weak. Cry was hypophonic. Initial labs (Table 1) did not provide a conclusive diagnosis. Ultrasound of the head and pylorus were negative. MRI brain and EEG were non-contributory. The initial working diagnosis was neuromuscular or metabolic disorder unmasked by acute viral illness, but genetic and metabolic testing was ultimately negative. Despite intermittent improvement in respiratory status, axial hypotonia and bulbar dysfunction persisted. Botulism stool culture obtained at DOL 32 and resulted positive at DOL 43 prompting treatment with botulism immunoglobulin.
Discussion: This case was a diagnostic conundrum for a few reasons – the broad differential diagnosis, the milder and slightly atypical presentation, the unclear toxin exposure, the extended turn-around time for the metabolic and genetic work-up, and the concomitant viral infection. The differential for an infant with hypotonia includes myotonic dystrophy, mitochondrial and neuromuscular disease, inborn errors of metabolism, neonatal myasthenia gravis, hypothyroidism, chromosomal disorders, drug/toxin ingestion, encephalitis, and sepsis. Clinical suspicion for botulism was not high at time of admission but increased as initial work-up was unrevealing, and the patient’s condition persisted. The main clinical features of botulism are hypotonia, constipation, lethargy, difficulty in sucking and swallowing, weak cry, pooled oral secretions, and muscle weakness. (1,3) Our patient had nonspecific feeding difficulties, hypotonia without constipation, and intermittently improving respiratory status in the setting of a viral illness. Additionally, there was no obvious source for botulinum toxin exposure such as ingestion of honey or living near active construction; however, parents did report using “Earth Mama Nipple Cream,” which contains beeswax and dad worked in construction. This case was not related to the recent recall of ByHeart Nutrition infant formula. (2) Published literature suggests that most cases of infant botulism do not have an identified source, (4) so index of suspicion should remain high. Treatment within the first three days is ideal; however, in our case, the initial clinical suspicion in that time frame was not high enough to justify the cost of treatment at over $69,000. (5) Our patient continues to work with outpatient physical and speech therapy for exercise and stretching but otherwise had full recovery.
Conclusions: Providers should consider botulism in all infants with unexplained hypotonia, even in the absence of classic presentation and exposure history.
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