Phosphoglycerate Dehydrogenase Deficiency

What else is it called?

  • 3-PGDH deficiency
  • 3-phosphoglycerate dehydrogenase deficiency
  • PHGDH deficiency

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What causes it?

PHGDH deficiency is autosomal recessive metabolic condition caused by mutations in the PHGDH gene cause phosphoglycerate dehydrogenase deficiency, this gene is involved in making an enzyme called phosphoglycerate dehydrogenase that breaks down the amino acid L-serine. Four PHGDH subunits combine to form the enzyme, if there is a mutation to this then the enzyme can only function partially or may not function at all, leading to a build-up of this metabolite. The metabolite being 3-phosphoglycerate to 3 phosphohydroxypyruvate which is the first step in serine metabolism. L-Serine is important in the development of your child’s spinal cord and functionality of their brain.

The lack of the amino acid L-serine likely prevents the production of proteins and the signalling molecules called neurotransmitters in the brain and impairs the formation of normal cells and myelin [a fatty sheath that surrounds and insulates the cells in the brain]. These disruptions in normal brain development lead to the signs and symptoms of phosphoglycerate dehydrogenase deficiency.

How common is it?

This condition is likely a rare disorder, but its prevalence is unknown. At least 15 cases have been described in the scientific literature. Due to the rare nature of this condition, it is difficult to determine whether it is more common in males or females. Further studies of this condition indicated that the carrier frequency in the Ashkenazi Jewish population was approximately 1 in 453.

What are the signs and symptoms?

Symptoms for this condition usually present from birth. However, as listed below, as the condition progresses so do a few of the symptoms. Some of the signs and symptoms of this condition are:

  • Microcephaly [small head circumference]
  • Psychomotor retardation
  • Seizures
  • Moderate developmental delay
  • Behavioural disorders appearing in infancy
  • Sensory neuropathy
  • Ataxia [group of disorders effecting balance, coordination and speech]
  • Feeding difficulties in infants

Most affected individuals have the infantile form, which is the most severe form, and are affected from infancy.Individuals with the infantile form of phosphoglycerate dehydrogenase deficiency develop many of the features described above. Symptoms of the juvenile and adult types appear later in life. Individuals with the juvenile form typically have epilepsy as well as mild developmental delay and intellectual disability. Currently, only one case of the adult form has been reported in mid adulthood, the symptoms of this being ataxia and numbness in arms and legs.

How is it diagnosed?

Diagnosis may occur via amino acid analysis in samples of your child’s urine or from a blood test sample. This test aims to check the levels of amino acid present within a sample to see if they are elevated or lower than expected to make a diagnosis. This may be done over a period of fasting in which the health care professional may ask your child to fast for up to 24 hours.

Previous literature reported that prenatal diagnosis can be made of an affected fetus by DNA mutation analysis [genetic testing].

Can it be treated?

Treatment with oral doses of L-serine has been shown to a reduce the amount of seizures an individual may experience (at a dose of 200 mg/kg/day divided into 3 doses). This has previously been given in an instance of pre-natal diagnosis, to which it the dose of L-serine was effective at increasing the head circumference percentile of a child. However, this Is more likely to be identified pre-Nataly if the adult or father Is a known carrier for this condition.

Treatment is also aimed at managing symptoms as they occur, such as seizures and feeding difficulties. Treatment will be discussed with you upon diagnosis and liaised with a multi-disciplinary team to attend to your child’s needs.

Do my family need to be tested?

PHGDH deficiency 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 are diagnosed, you can speak to a genetic counsellor. They can explain how you may have inheritedPHGDH deficiency. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own.

If you have previously had a child with PHGDH deficiency and go on to have further children, their New-born Screening test should be carried out within 24-48 hours of birth.

Relevant Organisations


References are available on request. Please contact Helen Morris by phoning 0845 241 2173 or emailing [Resource Library No: AAP002].

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