Amino Acid Metabolism Disorders: PKU, Maple Syrup Urine Disease and Others

Metabolism is how the body makes energy from food. Food is made of proteins, carbohydrates and fats, which the digestive system breaks down into sugars and acids — the body's fuel, used at once or stored. In a metabolic disorder, something in this process goes wrong.

Amino acid metabolism disorders

Amino acids are the building blocks that join to form proteins. In an amino acid metabolism disorder, the body may have trouble breaking down certain amino acids, or getting them into cells. Harmful substances then build up, which can cause serious, sometimes life-threatening, health problems.

• Inherited. These disorders are usually passed down in families.
• Screened at birth. A baby born with one may have no symptoms at first. Because the disorders can be so serious, early diagnosis and treatment are critical, and newborns are screened for many of them with blood tests.
• Treatment may include special diets, medicines and supplements; some babies need more treatment if complications arise.

Two of the best known are phenylketonuria and maple syrup urine disease.

Phenylketonuria (PKU)

PKU raises the level of phenylalanine, an amino acid found in foods such as meat, eggs, nuts and milk and in some artificial sweeteners. It is caused by variants in the PAH gene, which makes the enzyme phenylalanine hydroxylase; without enough working enzyme, phenylalanine builds up to toxic levels, and because brain cells are especially sensitive to it, the excess can cause brain damage.

• Classic PKU, the most severe form, occurs with very little or no enzyme activity. Babies seem normal for a few months; untreated, they develop permanent intellectual disability, and seizures, delayed development, behavioural problems and psychiatric disorders are common. Milder forms — variant PKU and non-PKU hyperphenylalaninemia — carry a smaller risk of brain damage.
• How common. In the United States PKU occurs in 1 in 25,000 newborns. Most cases are found by newborn screening and treated promptly, so the severe signs of classic PKU are rarely seen.
• Diet. PKU can often be managed with a low-phenylalanine diet: avoiding high-protein foods such as meat, dairy, nuts and tofu, a low-protein formula for infants, and avoiding the sweetener aspartame, found in diet soda. The safe amount differs from person to person, so diets are worked out with a health professional. Babies of mothers with PKU who are not following the diet are at significant risk of intellectual disability.

Maple syrup urine disease

In this disorder the body cannot properly break down three amino acids — leucine, isoleucine and valine — found in many foods, especially protein-rich ones such as milk, meat and eggs. It is named for the distinctive sweet smell of affected babies' urine, and causes poor feeding, vomiting, lack of energy, abnormal movements and delayed development; untreated, it can lead to seizures, coma and death.

• Forms. The classic type, the most common and severe, appears soon after birth. Variant forms appear later in infancy or childhood and are usually milder, but still cause delayed development and other problems if untreated.
• Cause. Variants in the BCKDHA, BCKDHB or DBT genes, which make parts of the protein complex that breaks the three amino acids down.
• How common. An estimated 1 in 185,000 infants worldwide — but about 1 in 380 newborns in the Old Order Mennonite population.

Sources

• MedlinePlus, U.S. National Library of Medicine, "Amino Acid Metabolism Disorders." https://medlineplus.gov/aminoacidmetabolismdisorders.html
• MedlinePlus Genetics, "Phenylketonuria" and "Maple syrup urine disease." https://medlineplus.gov/genetics/condition/phenylketonuria/ ; https://medlineplus.gov/genetics/condition/maple-syrup-urine-disease/
• Rewritten in hubnx's own words.