Sepiapterin and Dihydrobiopterin (CSF)

Cerebrospinal Fluid (CSF)

1.0 mL

0.5 mL

MNG supplied screw capped vial #3

Must be collected in tube 3 from supplied kit. Testing cannot be ordered if MNG collection kit not available

Freeze as soon as possible after collection

Room Temperature: Not stable; Refrigerated: Not stable; Frozen: 72 hours @ -20C, Indefinitely @ -80C; Freeze/Thaw: None

Bloody CSF; Received thawed

Measurement of sepiapterin and 7,8-dihydrobiopterin in CSF is useful for diagnosis of sepiapterin reductase deficiency and dihydropteridine reductase deficiency, both of which disrupt neurotransmitter biosynthesis. This testing may also be used for assessment of Variants of Uncertain Significance (VUS) identified during genetic testing (e.g. Next Generation Sequencing or Capillary Sequencing testing).  Sepiapterin and dihydrobiopterin are involved in tetrahydrobiopterin (BH4) metabolism. BH4 serves as a cofactor for the hydroxylation of phenylalanine and in the biosynthesis of the biogenic amine neurotransmitters. Sepiapterin reductase deficiency leads to accumulation of sepiapterin and dihydrobiopterin within CSF whereas dihydropteridine reductase deficiency only leads to accumulation of dihydrobiopterin, both disorders lead to decreased biogenic amine synthesis. Sepiapterin reductase deficiency results from mutations in the SPR gene and dihydropteridine reductase deficiency from mutations in the QDPR gene.

Although dihydropteridine reductase deficiency leads to hyperphenylalaninemia, sepiapterin reductase deficiency does not as other enzymes are present in the liver that can compensate for the lack of sepiapterin reductase activity. These compensatory enzymes are not found in the brain.

Disorders of BH4 metabolism are characterized by a wide range of symptoms that may include developmental delay, cognitive and mental delay, behavioral disturbances, dystonia, Parkinsonian symptoms, gait disturbances, speech delay, psychomotor delay and ptosis.

Diagnosis is important as effective treatments are already available.

Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS)

1. Bonafé L, Thöny B, Penzien JM, Czarnecki B, Blau N. Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia. Am J Hum Genet. 2001;69(2):269-277. doi:10.1086/321970
2. Blau N, Bonafé L, Thöny B. Tetrahydrobiopterin deficiencies without hyperphenylalaninemia: diagnosis and genetics of dopa-responsive dystonia and sepiapterin reductase deficiency. Mol Genet Metab. 2001;74(1-2):172-185. doi:10.1006/mgme.2001.3213
3. Friedman J, Roze E, Abdenur JE, et al. Sepiapterin reductase deficiency: a treatable mimic of cerebral palsy. Ann Neurol. 2012;71(4):520-530. doi:10.1002/ana.22685
4. Friedman J, Hyland K, Blau N, MacCollin M. Dopa-responsive hypersomnia and mixed movement disorder due to sepiapterin reductase deficiency. Neurology. 2006;67(11):2032-2035. doi:10.1212/01.wnl.0000247274.21261.b4

CSF Collection Tubes (set of 5 tubes per kit)