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Infantile spinal muscular atrophy

Spinal Muscular Atrophy (SMA) is a term applied to a number of different disorders, all having in common a genetic cause and the manifestation of weakness due to loss of the motor neurons of the spinal cord and brainstem. more...

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Caused by mutation of the SMN gene

The most common form of SMA is caused by mutation of the SMN gene, and manifests over a wide range of severity affecting infants through adults. This spectrum has been divided arbitrarily into three groups by the level of weakness.

  • Infantile SMA - Type 1 or Werdnig-Hoffmann disease (generally 0-6 months). SMA type 1, also known as severe infantile SMA or Werdnig Hoffmann disease, is the most severe, and manifests in the first year of life with the inability to ever maintain an independent sitting position.
  • Intermediate SMA - Type 2 (generally 7-18 months). Type 2 SMA, or intermediate SMA, describes those children who are never able to stand and walk, but who are able to maintain a sitting position at least some time in their life. The onset of weakness is usually recognized some time between 6 and 18 months.
  • Juvenile SMA - Type 3 Kugelberg-Welander disease (generally >18 months). SMA type 3 describes those who are able to walk at some time. It is also known as Kugelberg Welander disease.

Other forms of SMA

Other forms of spinal muscular atrophy are caused by mutation of other genes, some known and others not yet defined. All forms of SMA have in common weakness caused by denervation, i.e. the muscle atrophies because it has lost the signal to contract due to loss of the innervating nerve. Spinal muscular atrophy only affects motor nerves. Heritable disorders that cause both weakness due to motor denervation along with sensory impairment due to sensory denervation are known by the inclusive label Charcot-Marie-Tooth or Hereditary Motor Sensory Neuropathy. The term spinal muscular atrophy thus refers to atrophy of muscles due to loss of motor neurons within the spinal cord.

  • Hereditary Bulbo-Spinal SMA Kennedy's disease (X linked, Androgen receptor)
  • Spinal Muscular Atrophy with Respiratory Distress (SMARD 1) (chromsome 11, IGHMBP2 gene)
  • Distal SMA with upper limb predominance (chromosome 7, glycyl tRNA synthase)


The course of SMA is directly related to the severity of weakness. Infants with the severe form of SMA frequently succumb to respiratory disease due to weakness of the muscles that support breathing. Children with milder forms of SMA naturally live much longer although they may need extensive medical support, especially those at the more severe end of the spectrum.

Although gene replacement strategies are being tested in animals, current treatment for SMA consists of prevention and management of the secondary effect of chronic motor unit loss. It is likely that gene replacement for SMA will require many more years of investigation before it can be applied to humans. Due to molecular biology, there is a better understanding of SMA. The disease is caused by deficiency of SMN (survival motor neuron) protein, and therefore approaches to developing treatment include searching for drugs that increase SMN levels, enhance residual SMN function, or compensate for its loss. The first effective specific treatment for SMA may be only a few years away, as of 2005.


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Diagnosing infant botulism
From Nurse Practitioner, 3/1/01 by Cadou, Stephanie G

The Case

P.L., a 4-month-old female infant, presented with a 1 -week history of troubled feeding. The parents described the infant as "fussy" and reported a decrease in bowel movement frequency to once every 3 days for 2 weeks; the child's last bowel movement was 5 days prior to presenting.

History of Present Illness

P.L. had been healthy prior to her current symptoms. Recently, the parents noticed increased generalized weakness and decreased spontaneous activity. The mother noted choking during feedings and a weakened ability to suck.

P.L.'s past medical history is unremarkable. She is the result of a full-- term, spontaneous, vaginal delivery without prenatal or postnatal complications. She is current on her immunizations, has no known allergies, and is not taking any medications. She has been breast-fed since birth; her mother denies use of prescription, over-the-- counter, and illicit drugs.

Prior to her present symptoms, P.L. was fed five to six times a day without complications. She sleeps between 12 and 15 hours per day. She experienced one incidence of otitis media at age 3 months and was successfully treated with amoxicillin. She has a negative history of recent or past injuries, surgeries, or hospitalizations. The parents deny the infant's ingestion of honey and any history of neuromuscular disease, autoimmune disease, diabetes, asthma, bleeding disorders, seizure disorders, recent illness, fever, upper respiratory infection symptoms, rash, or excessive flatus.

Social and Family History

P.L. is the last of three children born to an intact, nonsmoking family. The family is financially secure and does not own any pets. The father is employed full-time outside the home and the mother stays at home. Occasionally, both maternal and paternal grandparents baby-sit the three children. For the "past few weeks," their neighbor has been constructing an addition to his house.

P.L.'s family history is negative for neuromuscular diseases, autoimmune diseases, diabetes, asthma, bleeding disorders, and seizure disorders. Her maternal grandfather is deceased from lung cancer, and her paternal grandmother and grandfather have hypercholesterolemia and hypertension.

Physical Examination

The physical examination revealed a blood pressure of 104 to 120/60 mm Hg, heart rate of 125 beats per minute, respiratory rate of 22 and regular, rectal temperature of 98.2 degF (36.7 deg C), weight of 12.5 pounds (40%), length of 24.5 inches (50%), and a head circumference of 16.5 inches (50%).

P.L. appeared well nourished, well developed, and in no apparent distress. Her skin was warm, dry, and fair; no lesions, rashes, ecchymosis, cyanosis, or jaundice were noted. She had good turgor and a capillary refill of less than 2 seconds.

Upon inspection, her face was hypotonic with a decreased expression, negative social smile, and mild ptosis bilaterally. Her anterior fontanelle was soft without bulging or depression. She had a positive head lag. Her pupils were equal, round, and reactive to light accommodation with extraocular movements intact. Her sclerae were white, the corneas were clear and regular, and the conjunctivae were pink without excess vascularity or discharge. The funduscopic examination was normal.

Her tympanic membranes were pearly gray with a positive cone of light and intact bony landmarks. Her lips and buccal mucosa were pink and moist without any lesions; her hard and soft palates were intact. She had a negative gag reflex, a decreased cough, and a decreased ability to correct her head position for an occluded airway. Her neck was supple with full range of motion. Her trachea was midline, and no lymphadenopathy was noted. Respiratory, cardiac, and peripheral vascular examinations were normal. Bowel sounds were slightly decreased in all four quadrants. Her abdomen was soft and nondistended with no organomegaly, masses, or hernia noted. Muscle strength was 3/5 to all groups with diffuse muscle weakness with full range of motion.

Neurologically, she responded to painful stimuli, had positive Babinski's reflex, and positive plantar and palmar grasps. She was admitted to the community hospital for rule-out sepsis and laboratory tests. A complete blood count and blood, urine, and cerebrospinal fluid cultures were all within normal limits. A culture of her stool was positive for Clostridium botulinum. Based on this result, she was immediately transferred to the county medical center and admitted to the pediatric intensive care unit for further observation, evaluation, and treatment.

* Discussion

Three forms of botulism exist: foodborne, wound, and infantile. All forms can be fatal and are considered medical emergencies. In the United States, approximately 110 cases of botulism are reported each year; 72% are infantile.1 Infant botulism is caused by a ubiquitous, obligate anaerobe, gram-positive bacillus C. botulinum.24

First diagnosed in California in 1976, infant botulism has a mortality rate of less than 3% in the United States.3,4 The bacteria form spores that allow them to survive in a dormant state until exposed to conditions that can support their growth. Infant botulism results from spore inhalation, ingestion, and subsequent outgrowth and in vivo toxin production in the intestine by bacteria.4 The toxin travels through the blood and causes a disruption of presynaptic neurotransmitter release. The toxin irreversibly binds to the synaptic membrane of cholinergic nerves, which prevents the release of acetylcholine.3

The toxin acts as a muscle paralysis agent. First, autonomic nervous system dysfunction occurs followed by motor weakness. Recovery and muscle control return only after the slowgrowing nerve cells regenerate. Because toxins bind at all ganglionic and postganglionic parasympathetic synapses, the typical signs of weakness occur in the distribution of both peripheral and cranial nerves.1,5-8

C. botulinum grows under anaerobic conditions and produces spores whose natural habitat is the soil.' Its spores are present on fresh fruit, vegetables, and other agricultural products such as honey.'9C. botulinum spores occur in almost 10% of U.S. honey supplies and have been linked to 20% to 35% of known infant botulism cases.4,8,10

Susceptibility, Resistance, and Incubation

Infants younger than age I and adults with altered gastrointestinal anatomy are most susceptible to infant botulism. Some 95% of infants who contract the illness are younger than age 6 months. The remaining 5% are distributed over the subsequent 6 months.8 Breast-feeding seems to slow the illness' onset, allowing time for hospitalization.8

Despite high levels of C. botulinum toxin and bacteria in the feces of patients for weeks to months after illness onset, cases of secondary transmission have not been documented.2, 10 A national seasonality is not evident. Cases have occurred in all major racial and ethnic groups, in equal proportions of male and female individuals, and have been reported in 43 of the 50 states and all continents except Africa.8 Approximately 50% of infant botulism cases occur in California; this may be a result of the state's warm, dry climate. Utah and southeastern Pennsylvania also have increased frequencies.9 The incubation period of infant botulism is unknown because ingestion of

C. botulinum spores cannot be precisely determined in infants.3,4,8-11

Diagnosis and Manifestations Diagnosis of infant botulism is based on clinical presentation and is confirmed by the identification of C. botulinum bacteria or toxin in the patient's feces. With few exceptions, the toxin has not been detected in the sera of patients.

The letters A through G are used to designate the seven types of immunologically distinct botulism toxin.1,10 Only types A, B, E, and F cause illness in humans. Most cases of infant botulism are caused by group I proteolytic type A or B.10-12

Infant botulism arises from ingestion of botulism spores that colonize and germinate in the intestinal tract, creating toxins. The bacteria interrupt neuromuscular transmission, which leads to paralysis by disrupting presynaptic neurotransmitter release.8 Infant botulism has a wide spectrum of clinical severity, ranging from mild illness with gradual onset to sudden infant death.

The illness typically presents with symptoms of muscle paralysis including constipation for at least 3 days; lethargy; listlessness; impaired gag, suck, and swallow reflexes; a weak cry; ptosis; an expressionless face; poor head control; hypotonia extending to generalized weakness; and, in some cases, respiratory insufficiency and arrest4,5,7-9 Although the classic first sign is almost always constipation, it is often overlooked.8,9 Because the toxin does not cross the blood-brain barHer to any functional degree, intelligence, personality, and sensation remain unaffected.1,7-12

Differential Diagnosis

Many symptoms of infant botulism mimic those of dehydration, electrolyte imbalance, diptheric polyneuropathy, neonatal myasthenia gravis, poliomyelitis, hypothyroidism, tick paralysis, Werdnig-Hoffmann spinal muscular atrophy, Leigh disease (subacute necrotizing encephalomyelopathy), congenital myopathy, Guillain-Barry syndrome, and exposure to toxins such as heavy metals and organophosphates.1,13,10 Rule-out sepsis remains the most common admission diagnosis for patients with infant botulism.8


Unfortunately, a vaccine does not exist to protect infants against infant botulism.11 Botulism antitoxin (an equine product), which is used to treat foodborne and wound botulism, is not appropriate for infant botulism because of sensitization and anaphylaxis hazards. Antibiotics do not improve the illness' course,9 and aminoglycoside antibiotics may even worsen the condition by causing a synergistic neuromuscular blockade.

Human botulism immune globulin (BIG) is available in the United States for infant botulism under an investigational drug protocol (see Table).9,10 BIG is a human pentavalent botulinal immune globulin that contains neutralizing activity against botulinal neurotoxin types A, B, C, D, and E.9,10

It inactivates toxins, including all toxins subsequently absorbed from the production site in the large intestine, before they can bind to nerve endings. A single intravenous infusion of BIG provides a protective level of neutralizing antibody against types A and B botulinum toxin for approximately 4 months. The cost of BIG is $1,650. In infants not treated with BIG whose weakness continues to advance, the nadir is generally reached within

I to 2 weeks after admission. Many remain at this stage for as long as 2 to 3 weeks before exhibiting improvement.9 BIG reduces hospitalization from 5.5 weeks to 2.5 weeks. BIG reduces the individual treatment cost by 50% to $60,000, for an annual savings of $2,000,000.5, 10 The reduced hospitalization time also reduces the emotional toll on the patient's family.35

Supportive care and mechanical ventilation remain the mainstay of treatment. Gastric lavage is used if food exposure was recent; cathartics or enemas are used, in the absence of ileus, to remove unabsorbed toxin from the gastrointestinal tract.10 Although intestinal motility is slow, enteral feedings are generally well tolerated and well absorbed. Enteral feedings also help restore bowel movements, which help eliminate the botulinum toxin and organisms from the large intestine.9

Despite the botulism's severity, infants almost always recover completely. In the absence of hypoxic cerebral complications, full and complete recovery of strength and tone can be expected. If infant botulism is not treated, death can result.7,8

Observed complications of infant botulism include adult respiratory distress syndrome; anemia; aspiration; bacteremia; C. difficile colitis, including toxic megacolon; fractures; osteopenia; funguria; inappropriate antidiuretic hormone secretion; misplaced or plugged endotracheal tube; otitis media; pneumonia; pneumothorax; recurrent atelectasis; seizures, usually secondary to hyponatremia; sepsis; tension pneumothorax; tracheal stenosis; transfusion reaction; and urinary tract infection.9

Infant botulism does not usually have a relapsing course. The presence of regression signifies additional complications or inadequate nutritional or respiratory support. The infant may be discharged when he or she has shown steady recovery and is able to feed by mouth. Although head lag and constipation may still be present, parents can be reassured that this is normal and that a full recovery will occur over time.9

* P.L.'s Outcome

P.L.'s case may have resulted from the inhalation of C. botulinum spores present in the airborne dirt from the neighbor's ongoing construction.

BIG was an appropriate treatment for P.L.10 Placement in the pediatric intensive care unit was warranted to ensure continual one-to-one assessment for potential complications and illness progression. Because she was at risk for respiratory failure, a thorough assessment was performed on her respiratory status. Intravenous fluids, expressed breast milk via nasogastric tube, neurological testing every

10 minutes, suctioning, and meticulous supportive care were essential to prevent complications. Additionally, lactulose was given via nasogastric tube three times per day for constipation, and artificial tears were used in each eye every 2 hours as needed for decreased blink.

P.L. was in the intensive care unit for 8 days and was then transferred to a pediatric floor for 5 days; she recovered without sequelae. She attended physical therapy on an outpatient basis twice a week for 16 weeks and regained full muscle strength and tone.

* Prevention

Primary care providers must educate patients on the dangers of feeding honey to infants younger than age 111 and the importance of handwashing. Foods that may be a source of the bacteria and any contaminated utensils should be boiled before discarded to prevent bacteria ingestion by animals. All canned and preserved foods should be properly processed and prepared. Malodorous foods should not be eaten or even tasted. I Commercial cans with bulging lids should be returned unopened to the vendor.8

Clinicians must also educate parents and caregivers about infant botulism signs and symptoms. Parents may be reassured that in uncomplicated cases, their child will reach motor milestones over time.9

Because reporting suspected and confirmed cases is obligatory in most states, clinicians should report all infant botulism cases to local and state health authorities. Clinicians may refer parents to the Infant Botulism Treatment and Prevention Program, which provides names and telephone numbers of other parents whose children have suffered from infant botulism.9


1. Centers for Disease Control and Prevention: Botulism: Frequently asked questions, 1999. botu.htm.

2. The Nemours Foundation: Infant botulism, 1999. botulism.html.

3. Amon SS: Infant botulism. In: Feigen RD, Cherry JD, eds. Textbook of pediatric infectious diseases. Philadelphia Pa.: W.B. Saunders Company, 1998;1570-77.

4. Utah Department of Health: Infant Botulism, 1997. http:/" epifacts/infantbo.html.

5. Botulism Infant Globulin Program, 1997. factsheets/25fs.htm.

6.Cotran RS, Kumar V, Robbins SL: Pathophysio

logic basis of disease, 5th edition. Philadelphia Pa.: W.B. Saunders Company, 1994;338-39.

7. New York State Department of Health: Communicable disease fact sheet: Botulism, 1996. http:/ botulism.htm.

8. Vanderbilt University Medical Center: Infant Botulism, 1998. pidl/neuro/botulism.htm.

9. California Department of Health Services: Infant botulism treatment and prevention program, 1999.

10. Shapiro RL, Hatheway C, Swerdlow DL: Botulism in the United States: A clinical and epidemiologic review. Ann Intern Med 1998;129(3):221-28.

11. Benenson AS: Control of communicable diseases manual. Washington, D.C.: American Public Health Association, 1995.

12. Hatheway CL: Botulism: The present status of the disease. Curr Top Microbiol Immunol 1995;195:55-72.

Cheryl Cummings Stegbauer, CFNP, PhD

Clinical Case Report Editor


Stephanie G. Cadou, RN, PNP, CS, MSN, is a pediatric nurse practitioner, Department of Pediatric Gastroenterology and Nutrition, Morristown Memorial Hospital, Morristown, N.J.

Copyright Springhouse Corporation Mar 2001
Provided by ProQuest Information and Learning Company. All rights Reserved

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