Normal Process:

1. Protein in food → broken down into amino acids
2. Amino acids are further processed into smaller compounds
3. Propionyl-CoA is converted into methylmalonyl-CoA by PCC
4. These products are used to produce energy safely

In Propionic Acidemia:

• PCC enzyme is missing or not working
• Propionyl-CoA cannot be processed
• Propionic acid and toxic by-products accumulate
• This leads to metabolic acidosis, high ammonia, and organ injury

Newborn Period (Most Common):

Symptoms often appear in the first days or weeks of life, especially after starting feeds:

• Poor feeding, vomiting
• Excessive sleepiness or irritability
• Weak or floppy muscles
• Rapid or labored breathing
• Low body temperature or fever
• Seizures or “staring spells”
• Episodes of shock or coma if untreated

Some milder cases present later:

• Poor growth (“failure to thrive”)
• Developmental delay or learning difficulties
• Recurrent vomiting or unexplained illness
• Movement problems (dystonia, tremors)
• Episodes of metabolic decompensation during infections or fasting

Even with treatment, children may develop:

• Neurologic issues – developmental delay, movement disorders, seizures
• Heart problems – cardiomyopathy, rhythm disturbances
• Pancreatitis
• Feeding problems – need for tube feeding in some
• Bone health issues – low bone density

Good early control and careful long-term management can reduce these risks.

1. Newborn Screening:

In many regions, PA is detected on the heel-prick newborn screen by measuring elevated propionylcarnitine (C3).

2. Confirmatory Testing:

If screening suggests PA:

• Blood and urine organic acids (high propionic acid, methylcitrate, 3-hydroxypropionate)
• Elevated ammonia, metabolic acidosis, high lactate during crisis
• Low carnitine levels
• Enzyme testing for PCC (in blood cells or skin cells)
• Genetic testing of PCCA and PCCB genes

Early diagnosis allows prompt treatment and helps prevent severe brain injury.

1. Special Diet (Foundation of Treatment):

Diet aims to limit precursors of propionic acid while allowing normal growth.

• Controlled natural protein intake (amount tailored to age and type of PA)
• Restriction of amino acids: isoleucine, valine, methionine, threonine
• Use of special medical formulas low in these amino acids
• Frequent meals and snacks to avoid fasting
• Adequate calories from carbohydrates and fats to prevent breakdown of body protein

A metabolic dietitian is essential to plan and adjust the diet.

Carnitine

• Helps bind and remove toxic organic acids in the urine
• Usually given daily (by mouth or via feeding tube)

Antibiotics (e.g., Metronidazole)

• Used intermittently to reduce gut bacteria that produce propionate
• Typically given in short courses (e.g., 7–10 days each month)

Supplements / Buffers

• Bicarbonate or citrate to correct chronic acidosis, if present
• Standard vitamins and minerals as needed

A crisis can be triggered by:

• Fever or infections
• Surgery or stress
• Poor intake, vomiting, or prolonged fasting

Warning Signs:

• Repeated vomiting
• Marked sleepiness or reduced responsiveness
• Fast or difficult breathing
• Unusual behavior or confusion
• Seizures

Emergency Treatment (Hospital):

• High-glucose IV fluids to stop protein breakdown
• Temporary stopping natural protein (using special emergency feeds)
• Treatment of high ammonia (medications or dialysis if severe)
• Correction of acidosis and electrolytes
• Prompt treatment of infection or other triggers

Families should have a written “sick-day” or emergency protocol to show local doctors.

Liver Transplant:

In selected children with:

• Recurrent life-threatening metabolic crises
• Poor metabolic control despite optimal treatment
• Progressive complications

Liver transplantation may:

• Reduce frequency and severity of crises
• Allow some relaxation of diet
• Improve quality of life

However:

• PA is a systemic disorder, so transplant does not completely cure it
• Heart and neurologic complications can still occur
• Lifelong immunosuppression and follow-up are required

Children with PA need ongoing care from a multidisciplinary metabolic team.

Typical monitoring includes:

• Growth (height, weight, head circumference)
• Nutritional status
• Blood gases, lactate, ammonia
• Organic acids and carnitine levels
• Heart evaluations (echo, ECG)
• Developmental assessments and school progress

Early detection of complications allows timely interventions.

Living with Propionic Acidemia:

With early diagnosis and careful management:

• Many children with PA can attend school, play, and participate in family activities.
• Families learn to manage special diets, recognize early signs of illness, and act quickly.
• Support from metabolic teams, dietitians, psychologists, and other families makes a big difference.

1. Never allow prolonged fasting – even overnight during illness.
2. Follow the diet and medication plan exactly.
3. Keep an emergency letter and contacts with you at all times.
4. Seek urgent care if your child is vomiting, very sleepy, or breathing fast.
5. Connect with support groups – you are not alone.

With the right care, many children and adults with propionic acidemia can lead active, meaningful lives.