A 3-month-old girl (EF) presents to the office of her primary care provider (PCP) with her parents, who report that the infant has been exhibiting fussiness and decreased appetite over the course of 48 hours. Over the last 24 hours, the mother has attempted feeding with both bottle and breast, but EF makes gurgling noises and stops feeding. EF has not had a wet diaper over the last 8 hours and her mother reports that the infant has been constipated for a “few days,” with her last bowel movement 4 days earlier.
EF was born via cesarean delivery at full term. Her Apgar score was 9/9, and the post delivery course was unremarkable. All newborn screening tests were negative. Well-child visits at 3 days, 2 weeks, 1 month, and 2 months demonstrated a healthy, well-developed normal newborn at the 70th percentile for length and 30th percentile for weight. Before these recent complaints, there were no feeding issues. EF is taking no medications and has no known allergies. Her parents’ health history is noncontributory.
On physical examination, EF is interacting appropriately with her parents (Table). All of her immunizations are up to date. On observation of attempted bottle-feeding, EF appears uncomfortable and makes gurgling noises and ceases feeding. There is no vomiting or spitting up after the feeding attempt. However, the lack of oral intake and dry diapers are concerning. The clinician has serious concerns about potential structural or neurologic issues, which prompts the provider to refer EF to the regional medical center for further evaluation and workup by pediatric services.
Emergency Department Visit
EF presents to the emergency department (ED) shortly after leaving the office of her PCP. She initially is seen by the ED pediatric resident. Her blood sugar level is noted to be 49 mg/dL. The infant tolerates a small amount of a mixture of oral electrolyte replacement and apple juice, which brings the glucose level up to 69 mg/dL. An intravenous (IV) line is placed, blood samples are taken for routine laboratory work, and a urine sample is sent for culture and toxicology screening. All results are reported as normal. Results of a lumbar spinal puncture also are normal.
A computed tomography scan of the head without contrast is normal as well. A pediatric abdomen series demonstrates nonspecific bowel gas patterns with dilated loops of bowel. Air also is noted in the rectum. A neurologic examination is notable for mild head lag, hypotonia with poor sucking, and minimal gag.
At this time, EF’s parents are advised that their child has a tentative diagnosis of botulism. The case is reviewed by pediatric intensive care unit attending clinicians and, based on EF’s stable condition, the hospital staff decide to admit her to the regular pediatric floor.
Botulism was first identified in the literature in the 1820s by German physician Justin Kerner. He correctly linked the disease to Clostridium botulinum toxins released from incorrectly prepared sausage and called it botulism after the Latin term for sausage, botulus.1
There are 8 known serotypes of botulism (A-H); types A and B are responsible for most cases of infant botulism. Most cases of botulism in North America are related to exposure to spores in dust or dirt, which can be kicked up or brought into the home on footwear or clothing. Honey is responsible for only 5% of cases of infant botulism in North America. Spores of C botulinum have been isolated from both pasteurized and nonpasteurized samples of honey; hence, it is recommended that honey be avoided until 12 months of age.2
Since 1980, infant botulism has been the most common form of human botulism in the US, with roughly 100 to 140 cases reported per year; approximately 90% of those cases occur in infants 6 months of age or younger with an age range of 1.5 days to 1 year.3 Most of these cases require hospitalization ranging from regular floor admissions to intensive care support. Botulism has been found worldwide.3
Once ingested, the botulism spores germinate and colonize in the gastrointestinal tract and release botulinum neurotoxins, which cause paralysis of the ileocecal valve and terminal ileum and, eventually, the entire bowel.3,4 The toxin is then released from the intestine and enters the systemic circulation, where it binds with presynaptic cholinergic receptors at motor nerve terminals. The toxin eventually disrupts exocytosis and inhibits the release of acetylcholine.4
Typical presentation of an infant with botulism starts with constipation, followed by poor feeding, and lethargy. Subsequently, deterioration progresses to symmetrical paralysis with the development of bulbar palsies demonstrated by an expressionless face, ptosis, head lag, and eye muscle paralysis.2,3 Gag, suck, and swallow reflexes also become impaired, with generalized weakness and decreases in deep tendon reflexes as the paralysis progresses.5
The onset of symptoms can vary from insidious — symptoms of constipation, weakness, lethargy, and poor feeding develop slowly over the course of a week — to abrupt — within 6 hours an infant goes from healthy to floppy; the latter often is misdiagnosed as meningitis.5 More than 70% of patients will require mechanical ventilation.4 Of note, the toxin does not cross the blood-brain barrier, so cognitive function is unaffected in these infants.2
Because botulism is rare, several conditions must be considered in the differential diagnosis when infants with neurologic symptoms present to the PCP or hospital. Although sepsis remains the most common initial diagnosis of these patients,5 Khouri et al categorized the clinical differential into the following in descending order of occurrence3:
- Spinal muscular atrophy (SMA) type 1
- Guillain-Barré syndrome, acute transverse myelitis, hypothyroidism, Chiari malformation, and cervical epidural hemorrhage
- Metabolic disorders: mitochondrial disorders, carnitine deficiency, congenital disorders of glycosylation, and urea cycle defects
- Infectious diseases: meningitis, polio-like enterovirus, parainfluenza with macrocephaly, and human metapneumovirus pneumonia
- Undetermined causes of botulism: dystonia, global developmental delay, and polyradiculopathy
The formal diagnosis of infant botulism is made through stool tests for the presence of toxins of C botulinum. Stool samples should be obtained as soon as possible, and treatment should be initiated as soon as infant botulism is suspected.