GTP Cyclohydrolase I Deficiency

What else is it called?

  • GTPCH deficiency 
  • Guanosine Triphosphate Cyclohydrolase I Deficiency 
  • Hyperphenylalaninemia due to GTP cyclohydrolase deficiency 
  • Hyperphenylalaninemia, tetrahydrobiopterin-deficient, due to GTP cyclohydrolase 1 deficiency 
  • Hyperphenylalaninemia, BH4-Deficient, B 

Get in touch

Contact our caring team on 08452 412 173 for help and support. Our phone lines open 10am-4pm, Monday to Friday.

Prefer to email? Our email address is

What causes it?

One of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine and tryptophan hydroxylases, both tetrahydrobiopterin-dependent hydroxylases.


How common is it?

This is an extremely rare disorder, less than five cases have been reported in the literature so far. 

What are the signs and symptoms?

When left untreated, the deficiency causes neurological signs at age 4 or 5 months, although clinical signs are often obvious from birth. The principal symptoms include:

  • Psychomotor retardation
  • Tonicity disorders
  • Convulsions
  • Drowsiness
  • Irritability
  • Abnormal movements
  • Hyperthermia
  • Hypersalivation
  • Difficulty swallowing

How is it diagnosed?

GTP-cyclohydrolase I deficiency should be suspected in all infants with a positive neonatal screening test for phenylketonuria, especially when hyperphenylalaninemia is moderate. The most effective way to diagnose the disorder is to measure pteridine levels in urine and to confirm the result by measuring neurotransmitters (5-hydroxyindolacetic acid, homovanillic acid) in cerebrospinal fluid and with an oral tetrahydrobiopterin-loading test (20 mg/kg). 

Can it be treated?

The treatment attempts to bring phenylalaninemia levels back to normal (diet with restricted phenylalanine intake or prescription of tetrahydrobiopterin) and to restore normal monoaminergic neurotransmission by administering precursors (L-dopa/carbidopa and 5-hydroxytryptophane). 

Do my family need to be tested?

This disorder can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier. 

If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have. 

If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.  

Once you receive a diagnosis, you can speak to a genetic counsellor. They can provide further information about inheritance and can also tell you about genetic testing for the rest of your family. 

Relevant Organisations

For more information, please visit Association for Glycogen Storage Disease UK.


References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing [Resource Library No: LSTO15]. 

Skip to content