Propionic Acidemia

Introduction
Propionic acidemia (PPA) is an autosomal recessive disorder of organic acid
metabolism. The deficiency of the enzyme Propionyl-CoA Carboxylase leads to the
accumulation of organic acid metabolites, when the infant or child is ingesting a normal
diet or under catabolic stress. This can be life threatening. Metabolic control with a
special diet and prompt treatment of illnesses decreases morbidity and mortality.

Clinical Features
Neonatal
Metabolic acidosis
Vomiting
Lethargy
Feeding problems
Infancy/childhood
Developmental delay
Seizure disorder
Metabolic decompensation during an intercurrent infection
Consequences
After episodes of metabolic decompensation, affected patients often suffer neurological
sequelae such as seizures, dystonia, chorea or mental retardation. Other known
complications of propionic acidemia include pancreatitis, leukopenia and
thrombocytopenia. Pre-symptomatic diagnosis and prompt treatment can probably
prevent or ameliorate complications.

Diagnosis
Newborn screen
Tandem mass spectrometry shows elevated propionylcarnitine (C3-carnitine)
Confirmation
Repeat newborn screen
Plasma acylcarnitines show increased propionylcarnitine
Urinary organic acids show increased propionyl-CoA metabolites (See figure)

Treatment
Avoidance of high protein foods
A special formula that does not offer the 'offending' amino acids valine, threonine,
isoleucine and methionine. This combination of low protein foods and formula will provide
the amino acids and nutrients necessary for normal growth and development while
restricting the intake of the "offending" amino acids. In order to ensure the balance
between the different amino acids, additional supplementation of isoleucine and valine
sometimes become necessary. Carnitine supplementation aims at promoting reduction of
the toxic propionyl-CoA by converting it to propionylcarnitine, which is readily excreted in
the urine. Patients with propionic acidemia may respond to regular courses of
metronidazole or other antibiotics to reduce the bulk of propionic acid producing gut
bacteria. A common (and desirable) side effect of carnitine is the softening of stools, but
sometimes the patients need additional help with lactulose or even more aggressive
defecants. Patients often will resist feedings after the first year of life and require feeding
gastrostomies. Some patients will regain the ability to eat in later childhood.

Situations that risk metabolic decompensation
Metabolic decompensation in children with propionic acidemia can be triggered by the
catabolism associated with infection, post-immunization or during a period of prolonged
fasting. Because catabolism is usually accompanied by the accumulation of toxic
metabolites, administration of carnitine is especially important in these situations. In
addition, hot weather requires extra fluid administration such as water, pedialyte or fruit
juice.

Monitoring
Ketonuria can be an early sign of metabolic decompensation and frequently precedes
clinical signs. Therefore urinary ketones should be checked at home on a daily basis.
Mild or moderate ketonuria indicates a catabolic situation and requires immediate
management in conjunction with a metabolic physician. Recurrent vomiting or refusal to
eat also requires immediate management and metabolic consultation. The management
generally includes early aggressive treatment of infections, administration of fluids and
calories, mainly in the form of carbohydrates and fat as well as assurance of adequate
carnitine administration. The children may need to be taken to the emergency room for
IV fluids and 10% glucose. Parents usually have an emergency protocol with them that
contains basic information about the disorder as well as appropriate diagnostic
evaluations and emergency treatments.

Infection/Immunization
Any infection can potentially lead to metabolic decompensation. Therefore its prevention
and/or early intervention is of particular importance. For this and other reasons
immunizations must be kept on track. This includes a yearly vaccine for influenza for
all children with propionic acidemia. There is no contraindication to immunization
because of propionic acidemia, but patients and physicians should be alerted to the
need for immediate evaluation if high fever, lethargy or vomiting occurs in the first 24h.
After an immunization without any other clinical symptoms, administration of acetaminophen
or ibuprofen is warranted.

Surgical/surgical procedures
Infants and children with propionic acidemia can undergo necessary surgical/surgical
procedures. However, since a surgical procedure constitutes a potentially catabolic
situation, any surgery should include hospitalization pre- and postoperatively.
Preoperative fasting should be avoided with 10% dextrose being started preoperatively
and continuing postoperatively until the child is eating/drinking well. If complicated
surgery, or a postoperative period as an inpatient is required, this should be carried out
at a hospital with a metabolic service.

Growth and development
All children with PPA follow a restricted diet that requires closely monitor all growth
parameters on a regular basis. During visits to the metabolic center, dietary adjustments
are usually made according to growth measurements and levels of amino acids and other
nutrients. Children with propionic acidemia can suffer from neurological impairment
such as developmental delay, seizures, dystonia or chorea, usually the results of a
severe metabolic crisis. Even with pre-symptomatic diagnosis and treatment, these
children are still at risk for developing neurological problems. If there are concerns about
the neurological development, the child should be integrated into an early intervention
program and developmental progress closely monitored by both the metabolic team and
the primary care provider.

Figure