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  • Test code: 06148
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Disorders of Serine Biosynthesis Panel

Test description

The Invitae Disorders of Serine Biosynthesis Panel analyzes 3 genes that are associated with disorders of serine biosynthesis. These genes were selected based on the available evidence to date to provide Invitae’s broadest test for disorders of serine biosynthesis. Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of disease-causing variants provides risk assessment and carrier status for at-risk relatives.

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Primary panel (3 genes)
  • phosphoglycerate dehydrogenase deficiency
  • phosphoserine aminotransferase deficiency (PSATD)
  • phosphoserine phosphatase (PSPH) deficiency

The disorders of serine biosynthesis, comprise a group of three neurometabolic diseases caused by reduced levels of CSF and plasma serine. These disorders exhibit a wide phenotypic spectrum, ranging from a congenital lethal form, also known as Neu-Laxova syndrome (NLS), an infantile form, to a milder childhood form. NLS is a multiple congenital anomaly disorder characterized by ichthyosis, intrauterine growth restriction, severe microcephaly, a short neck, central nervous system anomalies (lissencephaly, hypoplastic cerebellum, enlarged ventricles, decreased/absent gyri, agenesis of the corpus callosum), significant edema of the hands and feet, limb anomalies, flexion deformities, hypoplastic external genitalia, hypoplastic lungs, and distinctive dysmorphic features. These manifestations are severe and usually result in prenatal or early postnatal lethality. Patients with the intermediate infantile form of a serine biosynthesis disorder typically present with IUGR, microcephaly, feeding difficulties, vomiting, nystagmus, hypertonia which may lead to spastic tetraplegia, and seizures. Onset occurs within the first few months of life. Patients will typically have poor psychomotor development, abnormal brain imaging findings such as brain atrophy, enlarged ventricles, hypomyelination, and a hypoplastic cerebellum. Other features may include congenital cataracts, adducted thumbs, inguinal and umbilical hernias, hypogonadism and megaloblastic anemia. The milder childhood onset form typically presents at several years of age. Features include developmental delay, intellectual disability, behavioral abnormalities, seizures, and hypertonia. Ataxia and polyneuropathy have been reported in adult patients.

L-serine supplementation has been reported to alleviate some of the symptoms of serine biosynthesis disorder. Better outcomes have been reported when treatment onset was started soon after birth or even prenatally, presumably when less irreversible neurological damage has occurred.

PHGDH, PSAT1, PSPH are the only genes known to be associated with systemic serine deficiency. However, due to the rarity of this condition, the percent of systemic serine deficiency attributed to pathogenic variants in these genes is currently unknown.

Serine biosynthesis disorders are inherited in an autosomal recessive manner.

The prevalence of serine deficiency syndrome is very rare, with only a handful of published cases.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
PHGDH NM_006623.3
PSAT1 NM_058179.3
PSPH* NM_004577.3

PSPH: Deletion/duplication and sequencing analysis is not offered for exons 4-5 (NM_004577.3).