Pediatric dysautonomias often reflect problems or mutations which occur during the development of the autonomic nervous system. They are typically diagnosed within the first few years of life. This article gives a brief description of several rare pediatric autonomic disorders. [Although POTS (postural orthostatic tachycardia syndrome) may occur when a person is still seeing a pediatrician, it is not a genetic or congenital autonomic disorder.]
Familial Dysautonomia (FD)
One type of mutation, found almost exclusively in people of Ashkenazi Jewish heritage, affects the autonomic and sensory nervous system development. This is known as familial dysautonomia (FD). This is a genetic mutation passed down from the parents. Both parents must carry a gene mutation. This mutation impacts the production of a protein that helps the nervous system develop. Sometimes FD is referred to as Riley-Day syndrome or type III hereditary sensory and autonomic neuropathy (HSAN type III).
The nerve fibers of those who have FD do not work properly. This impacts the sensory nervous system (e.g., sensitivity to pain and temperature, ability to taste) and the following bodily functions:
- Blood pressure regulation: orthostatic hypotension (low blood pressure) when standing
- Body temperature regulation
- Digestion: difficulty swallowing (dysphagia), inability to suck, chronic acid reflux
- Respiratory: poor control of breathing, especially during sleep
- Salivation: excess saliva
- Tear formation: absence of tears/dry eyes
FD carries an increased risk of developmental delays and shorter life expectancy. For more information about familiar dysautonomia:
Phenylketonuria (PKU)
Phenylketonuria (PKU) is another inherited gene mutation.
PKU causes an increased level of phenylalanine (fen-ul-key-toe-NU-ree-uh) in the bloodstream resulting in a metabolic disorder. Native Americans and people of European descent are at a higher risk of having PKU.
Phenylalanine (Phe) is an amino acid. People with PKU lack the enzyme their body needs to break down this amino acid. Left untreated, phenylalanine builds up in the body. This can result in developmental delays and other symptoms that include:
- Eczema
- Neurological problems that could include seizures
- Small head size (microcephaly)
- Musty odor emanating from the breath, skin, or urine
- Skin and/or hair discoloration (typically lighter in color than biological family members)
Babies born in the United States are screened for PKU. Cases of PKU are classified as severe, moderate, and least severe. PKU can be treated with medication and by following a special diet low in phenylalanine.
For more information about PKU:
Menkes Disease
Menkes disease is a genetic disorder resulting from a mutation in the ATP7A gene. This gene affects the body’s ability to produce a protein that regulates the metabolism of copper in your body. The body needs copper to keep the body systems working properly (e.g., nervous systems, bone, skin, blood vessels, hair). When this gene is not working there are abnormally low levels of copper in the liver and brain and abnormally higher levels in the kidney and intestinal lining.
Symptoms typically begin 8-12 weeks after birth and primarily affect males of all ethnicities. Some of the symptoms include:
- Seizures (epilepsy)
- Failure to thrive (slow growth and weight gain)
- Floppy muscle tone (hypotonia)
- Facial features that sag
- Sub-normal body temperature (hypothermia)
- Kinky hair that breaks easily and is light in color
- Yellowish skin and eyes (jaundice)
Menkes disease cannot be screened for at birth. Because symptom onset is typically subtle and early detection is rare, early intervention that makes a significant difference is uncommon. There is no cure for Menkes disease. Most treatment is symptomatic and supportive. Children with Menkes typically have a life expectancy of less than 10 years.
For mor information about Menkes disease:
Hirschsprung’s Disease
Hirschsprung’s disease is a congenital condition in which there is a lack of development of nerve cells in the enteric (intestinal) nervous system. These nerve cells, also known as ganglion cells, are missing in a part of the intestines. Without them the bowel wall cannot contract and push waste through the intestines. This can cause blockages. Symptoms can present shortly after birth or later in older infants and children depending upon how mild or severe the case.
Symptoms commonly seen in infants:
- Delayed passage of meconium (newborn’s first bowel movement)
- Constipation or gas resulting in a fussy baby
- Swollen belly
- Difficulty or straining when having bowel movements
- Vomiting
- Diarrhea or infrequent but explosive stools
- Jaundice (yellow skin and eyes)
- Poor weight gain
Symptoms commonly seen in older children:
- Malnutrition (failure to thrive)
- Gas
- Swollen belly
- Constipation that gets worse over time
- Fecal impaction
- Fatigue
Hirschsprung’s disease is usually treated with surgery to remove the affected portion of the intestine and rectum. Children with milder cases who are treated early have the best outcomes.
For more information about Hirschsprung’s disease:
Hereditary Sensory and Autonomic Neuropathy (HSAN)
Hereditary sensory and autonomic neuropathies (HSAN) are a group of rare disorders that typically present in childhood. They include distinct but similar disorders of the peripheral nervous system (nerves outside of the brain and spinal cord). These disorders are associated with varying degrees of sensory dysfunction and have the potential to cause autonomic problems. If the autonomic nerves are affected, these bodily functions may be also:
- Blood pressure and heart rate control
- Gastrointestinal motility
- Body temperature regulation
- Sweating
- Pupil control
The following are brief descriptions of HSAN types. (Note: These are introductions to and not comprehensive medical description of each type of HSAN.)
HSAN type I (HSANI), also referred to as hereditary sensory radicular neuropathy, is a degenerative disorder of the nervous system (neurodegenerative) affecting sensory nerves which often leads to loss of sensation in the hands and feet. In some cases, patients experience shooting pain in their legs and feet. This abnormal function of the sensory nerves may also impact the autonomic nervous system.
For more information on HSAN1:
HSAN type II (HSANII) affects the nerves that serve the lower portion of the legs and arms including feet and hands. Symptoms include inflamed fingers and toes, progressive loss of sensation in the hands and feet. This type can also impact the autonomic nervous system that controls the automatic processes of the body including sweating, tear production, and low blood pressure when standing (postural hypotension).
For more information on HSANII:
HSAN type III (HSANIII): Also known as familiar dysautonomia (FD). Description given above.
HSAN type IV (HSANIV) typically begins in infancy. It is caused by a mutation of the NTRK1 gene which causes congenital insensitivity to pain (CIPA) with anhidrosis (the inability to sweat). The sensory nerves do not control responses to pain and temperature. Symptoms include the inability to feel temperature (distinguishing between hot and cold). Anhidrosis can lead to fevers and high body temperature because the body does not sweat and cool itself.
For more information about HSAN types II, III, IV:
HSAN type V (HSANV) is caused by a mutation in the NGFB gene.
It’s like HSANIV in that it’s a congenital insensitivity to pain and temperature sensations but with partial anhidrosis (loss of perspiration). Because of the inability to feel deep pain, patients may experience repeated severe injuries such as joint or bone fractures.
For more information about HSANV:
Congenital Central Hypoventilation Syndrome (CCHS)
CCHS is a very rare neurological disorder. It’s considered to be an extreme manifestation of autonomic nervous system dysregulation. The most significant and recognizable symptom is the body’s inability to control the basic respiratory function of breathing. Onset is most common within the first four weeks after birth with much less common, mild cases being diagnosed later in life.
Symptoms include:
- Hypoventilation (breathing at an abnormally slow rate which increases carbon dioxide in the blood)
- Acid reflux and feeding difficulties
- Decreased intestinal motility (constipation)
- Hirschsprung’s disease (see description above)
- Temperature dysregulation
- Abnormal pupillary response
This disorder is managed by multidisciplinary specialists. Treatment goals include providing breathing support which typically includes the use of a respirator or ventilator. CCHS is a chronic, lifelong disorder, but with treatment, patients have a normal life expectancy.
For more information about CCHS:
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
CPVT is a rare genetic defect that causes arrhythmias (sudden irregular heart rhythm) in children. Most often this presents as episodic syncope (fainting), but those affected by CPVT may also just feel like they are going to faint. Some patients have seizures. Often episodes of arrhythmias happen during exercise or during times of emotional distress. This can cause heart palpitations and even cardiac arrest. In some cases, these arrhythmias resolve. However, tachycardia (heart rate over 100 beats per minute) can progress to ventricular fibrillation (a life-threatening heart rhythm in which the heart doesn’t pump blood to the rest of the body).
The average onset of symptoms is between the ages of seven and twelve with some cases of onset occurring in adulthood. Because ventricular fibrillation is a risk, treatment is critical. The most common treatment options include medicinal options, implantable cardioverter defibrillators (ICD), and lifestyle changes when needed. The prognosis for CPVT is poor.
For more information about CPVT:
Summary
Although pediatric autonomic disorders are rare, they do occur. If you suspect your child has a pediatric autonomic disorder, it’s important to find a provider who understands pediatric autonomic disorders. We have several pediatric providers in our provider list.
Video Resource: Pediatric Dysautonomias presented by Dr. David S. Goldstein. Chief, Autonomic Medicine Section NINDS, National Institute of Health
