OVERVIEW

What is a branched-chain amino acid metabolism disorder?

The main branched-chain amino acids in the human body are leucine, isoleucine, and valine, which cannot be synthesized by the body and must be obtained from food.

If any step in the degradation process of these three branched-chain amino acids is disrupted, it can lead to the accumulation of the amino acids themselves and their metabolic intermediates (mainly keto acids) in the body. This condition is called a branched-chain amino acid metabolism disorder, which is a broad category of congenital genetic diseases.

Keto acids are toxic to the human nervous system. Therefore, branched-chain amino acid metabolism disorders often manifest as feeding difficulties in infancy, central nervous system damage, and metabolic acidosis. Without timely and proper treatment, affected infants often die during infancy.

Are branched-chain amino acid metabolism disorders common?

Branched-chain amino acid metabolism disorders are congenital genetic diseases. They are not common and are considered rare disorders.

SYMPTOMS

What are the common manifestations of branched-chain amino acid metabolism disorders?

Branched-chain amino acid metabolism disorders often occur in infancy, with diverse and highly heterogeneous manifestations ranging from asymptomatic to severe symptoms. Typical manifestations include gradually appearing vomiting, feeding difficulties, and weight loss within days after birth; alternating lethargy, irritability, decreased and increased muscle tone; frequent paralysis, seizures, and coma; the infant's sweat and urine may have a distinctive odor.

CAUSES

What causes branched-chain amino acid metabolism disorders?

Branched-chain amino acid metabolism disorders are a group of inherited diseases caused by parents passing defective genes to their offspring, leading to deficiencies in certain enzymes and resulting in metabolic disorders of branched-chain amino acids.

Are branched-chain amino acid metabolism disorders contagious?

Branched-chain amino acid metabolism disorders are not contagious.

How are branched-chain amino acid metabolism disorders inherited?

Branched-chain amino acid metabolism disorders follow an autosomal recessive inheritance pattern. Simply put:

• If both parents show no symptoms but carry the disease-causing gene, their offspring have a 25% chance of developing the disorder.

• If one parent has the disease and the other carries the disease-causing gene, their offspring have a 50% chance of developing the disorder.

DIAGNOSIS

How is branched-chain amino acid metabolism disorder diagnosed?

When diagnosing branched-chain amino acid metabolism disorders, doctors primarily determine whether the levels of branched-chain amino acids and their metabolites are elevated.

What tests are needed to diagnose branched-chain amino acid metabolism disorders?

Generally, tests for branched-chain amino acids and their metabolites, CT or MRI scans, and genetic mutation analysis are required.

• Tests for branched-chain amino acids and their metabolites: Primarily used to confirm the diagnosis. Samples may include urine, blood, or even dried blood spots.

• CT or MRI scans: Mainly used to assess the condition of the nervous system and are not the basis for diagnosis.

• Genetic mutation analysis: Primarily used to confirm the diagnosis.

TREATMENT

Which department should I visit for branched-chain amino acid metabolism disorders?

Pediatrics, Endocrinology, Neonatology.

Can branched-chain amino acid metabolism disorders resolve on their own?

Branched-chain amino acid metabolism disorders are congenital genetic diseases and will not resolve without treatment. Without timely intervention, affected infants are at high risk of death.

How are branched-chain amino acid metabolism disorders treated?

Treatment methods for branched-chain amino acid metabolism disorders primarily include dietary therapy, metabolic decompensation treatment, liver transplantation, etc.

• Dietary therapy: The main goal is to reduce toxic metabolites, maintain branched-chain amino acid levels within the normal range, support normal growth, and protect intellectual function and development. This involves restricting branched-chain amino acid intake through specialized formula and medical foods. Dietary restrictions must be maintained for life.

• Metabolic decompensation treatment: Measures such as glucose infusion and amino acid supplementation aim to inhibit protein catabolism and promote protein synthesis, rapidly lowering branched-chain amino acid levels in blood and tissues. In cases of cerebral edema, dehydration and diuretic treatments are administered. In rare cases, hemodialysis or peritoneal dialysis may be required to remove branched-chain amino acids and their metabolic intermediates.

• Liver transplantation: For maple syrup urine disease (a type of branched-chain amino acid metabolism disorder), liver transplantation may be considered.

DIET & LIFESTYLE

Do branched-chain amino acid metabolism disorders require re-examination? How to re-examine?

Branched-chain amino acid metabolism disorders require regular re-examination.

• For infants who develop symptoms after birth, it is recommended to monitor weekly for those under 3 months of age, every 2 weeks to 1 month for infants aged 3–12 months, and then monthly thereafter. The monitoring involves measuring plasma amino acid concentrations, and the intake of branched-chain amino acids should be adjusted based on the test results.

• For patients who develop symptoms after infancy, it is recommended to monitor plasma amino acid concentrations monthly until the levels stabilize, after which monitoring should be conducted every 3–6 months.

PREVENTION

How to prevent complications in patients with branched-chain amino acid metabolism disorders?

Although branched-chain amino acid metabolism disorders cannot be cured, timely and proper treatment can help affected children survive and improve symptoms, especially during the first year of life. Newborn screening, early diagnosis, and active, appropriate treatment are key to preventing complications.