GTP Cyclohydrolase Deficiency

What is GTP Cyclohydrolase Deficiency?

GTP cyclohydrolase deficiency is a rare, genetic, metabolic disease. Tetrahydrobiopterin is a natural substance, a coenzyme that enhances the action of enzymes. In other words, tetrahydrobiopterin helps enzymes break down protein in the body. In GTP Cyclohydrolase deficiency there isn’t enough tetrahydrobiopterin in the body. This leads to high levels of an amino acid (building block of protein) called phenylalanine and low levels of neurotransmitters (help transport information from the end of one nerve to the beginning of the next).
What symptoms are associated with GTPCH Deficiency?
A wide range of symptoms can be associated with GTPCH Deficiency, and involvement
can vary from mild, moderate to severe. This disorder is typically associated with diurnal
fluctuation, meaning the symptoms worsen as the day progresses.

Mild: In the mildest cases often the dominant form of GTPCH walking or running may be
clumsy but little else may be noticed initially. Onset often begins with a postural dystonia
(abnormal positioning) of one extremity (often the leg) which typically occurs around 6
years of age. Postural tremor (a rhythmic, involuntary muscular contraction which
occurs during a fixed arm position or posture) is also common. Symptoms may progress
slowly as the child gets older. Children with mild symptoms are often treated
successfully with medication.

Moderate: In moderately affected cases, the child may not be able to walk at all, or
walking may be extremely difficult. Abnormal eye movements, postural tremor and
speech delay may be present. Children with moderate symptoms often respond well to
treatment but full benefit of treatment may take many months.

Severe: In the most severe cases children are physically disabled and affected from
early infancy. This may be considered to be the recessive form of the disorder, and may
be detected through newborn screening for phenylketonuria. Patients may demonstrate
all or some of the following symptoms:

Muscle tightness (rigidity, spasticity)
Abnormal posturing (arching of the back)
Poor muscle control
Abnormal eye movements (eye deviation upward, downward or towards
the nose)
Strabismus (cross-eyed)
Ptosis (droopiness of the eyelids)
Speech delay
Difficulties feeding or swallowing
Torticollis (involuntary deviation of the head and neck to one side)
Intermittent color changes
Unexplained low body temperatures or fevers
Low blood sugar
Difficulty regulating blood pressure
EEG abnormal brain wave spiking (misfiring)
What causes GTPCH Deficiency?
GTPCH can be inherited dominantly, recessively or rarely as a compound heterozygote
(falling somewhere between the two previous phenotypes). When inherited as an
autosomal recessive trait, GTPCH Deficiency does not occur unless an individual
inherits the same defective gene for the same trait from each parent. A child who
receives one normal gene and one gene for the disease may be a carrier and possibly
not show symptoms, or may be affected with the less severe dominant form of GTPCH.
The risk of transmitting the recessive form of the disease to the children of a couple,
both of whom are carriers for a recessive disorder is 25%. The risk is the same for each
and every pregnancy.