Neu Laxova syndrome

Neu Laxova syndrome (NLS) can be caused by mutations in three different genes, PHGDH, PSAT1, and PSPH. The syndrome is currently classified in type 1 and type 2 when caused by mutations in the genes PHGDH and PSAT1, respectively. The mutations in PSPH causing NLS have not yet been classified as a different type.^[1][2][3] 

These 3 genes, PHGDH, PSAT1 and PSPH, are the instructions (code) for making the enzymes needed to make the amino acid L-serine. L-serine has important functions in the body. Since L-serine is an amino acid, it is one of the building blocks used to make many different proteins our body needs. It is also used to make other important compounds needed throughout our body and helps the brain develop normally.^[1][2][3]

Neu Laxova syndrome (NLS) can be considered as part of a group of diseases known as “serine biosynthesis defects”.^[1] Serine biosynthesis defects result from different mutations in the PGDH, PSAT, or PSPH genes that lead to serine deficiency throughout the whole body (systemic). The serine biosynthesis diseases include:^[2][4]

• Neu-Laxova syndrome - the most severe form
• Infantile serine biosynthesis deficiency - intermediate form with growth deficiency, small head, brain malformations, severe developmental delay, and severe neurological problems including seizures and stiff and rigid muscles (affects ability to move and develop speech).
• Childhood serine biosynthesis disease - the mildest form with normal growth and brain development, milder developmental delay, and seizures.

The difference between NLS and the other related syndromes is the amount of working protein that is made. In the case of NLS, the mutations in the genes do not allow very much working protein to be made at all. In other words,  because of the mutation, one of the enzymes needed to make L-serine is almost completely inactive, so very little L-serine can be made in the body.^[4]

Understanding that the symptoms of these diseases are caused by having too little L-serine is very important for future treatment, because giving L-serine before the neurological damage happens may be prove to be an effective therapy.^[3][4]

Neu-Laxova syndrome (NLS) is inherited in an autosomal recessive manner. This means a a baby must have a mutation in both copies of one of the three gene which can cause NLS. In other words, a baby with NLS will have a mutation in both copies of the PHGDH, PSAT1 or PSPH gene.^[3][4] 

Babies with NLS inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition, like NLS, usually do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% chance to be affected
• 50% chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not a carrier

The brother or sister of a baby with NLS will have a 2/3 (66%) chance of being a carrier of NLS and a 1/3 chance of not being a carrier. The only way a carrier of NLS has a risk of having a child with NLS is if their partner carriers a mutation in the same NLS related gene. However there are other related forms of L-serine biosynthesis defects which are also caused by mutations in the same genes, so talking to a genetic counselor or genetic specialist before becoming pregnant is important. ^[3][4]

Most cases of Neu Laxova syndrome have a poor prognosis. Many affected newborns either are stillborn, or die soon after birth or during the first weeks of life.^[5][6] However, Neu Laxova syndrome can be considered as part of the “serine biosynthesis defects” which includes Neu Laxova and other conditions that are less severe (Please see our information about causes) and may have a better outcome.