Diseases Studied

Defects in biopterin synthesis or recycling, or tetrahydrobiopterin deficiency (BH4 Deficiency), is a general term for a group of disorders characterized by abnormalities in the creation (biosynthesis) or regeneration of tetrahydrobiopterin, a naturally-occurring compound that acts as a cofactor. In most of these disorders, there are abnormally high levels of the amino acid phenylalanine (hyperphenylalaninemia). Symptoms can include progressive neurological abnormalities, lack of muscle tone (hypotonia), the overproduction of saliva (hypersalivation), loss of coordination, abnormal movements, and/or delayed motor development. The four main forms of the disorder include:

• GTP cyclohydrolase 1 Deficiency
• 6-Pyruvoyl-Tetrahydropterin Synthase Deficiency
• DihydropteridineReductase Deficiency
• Pterin-4a-Carbinolamine Dehydratase Deficiency

DNAJC12 deficiency is a rare inborn error of metabolism characterized by increased serum phenylalanine. It is associated with various neurological symptoms ranging from mild autistic features or hyperactivity to severe intellectual disability, dystonia, and parkinsonism. Laboratory analyses show normal tetrahydrobiopterin (BH4) metabolism and low levels of the CSF monoamine neurotransmitter metabolites homovanillic acid and 5-hydroxyindoleacetic acid.

A genetic disorder causing high blood levels of the amino acid phenylalanine. This condition also causes abnormally low levels of neurotransmitters, which transmit signals between nerve cells in the brain. When not treated, symptoms include abnormalities of muscle tone, delays in motor development, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing.

A genetic disorder causing high blood levels of the amino acid phenylalanine. This condition also causes abnormally low levels of neurotransmitters, which transmit signals between nerve cells in the brain. When not treated, symptoms include abnormalities of muscle tone, delays in motor development, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing.

A genetic disorder causing high blood levels of the amino acid phenylalanine. This condition also causes abnormally low levels of neurotransmitters, which transmit signals between nerve cells in the brain. Symptoms include abnormal muscle tone, poor head control, seizures, and delayed motor development. Without treatment, the condition can cause permanent intellectual disability.

A genetic metabolic disorder that increases the body's levels of the amino acid phenylalanine. People with PKU cannot properly break down the extra phenylalanine in the food they eat, which allows it to build up in the person's blood, urine, and body. When left untreated, phenylalanine can build up to harmful levels. PKU varies from mild to severe. The most severe form is known as classic PKU. Without treatment, children with classic PKU develop permanent intellectual disabilities.

A genetic disorder causing high blood levels of the amino acid phenylalanine. When left untreated, symptoms include decreased muscle tone, irritability, and delays in motor development. Neurological development is normal with dietary control of blood phenyalanine.