Serine Biosynthesis and Transport Defect – SBTD

Baby Detect > Metabology > Serine Biosynthesis and Transport Defect – SBTD

PHGDH, PSAT1, PSPH, SLC1A4 genes

Also known as: Serine deficiency; Neurometabolic disorder due to serine deficiency; Neulaxova spectrum; Neulaxova syndrome.

Include:

  • Spastic Tetraplegia, Thin Corpus Callosum, and Progressive Microcephaly – gene SLC1A4

1. The disease

Serine biosynthesis defects result from impairments of PGDH, PSAT, or PSP leading to systemic serine deficiency. Serine-deficiency syndrome is a very rare infantile-onset potentially treatable neurometabolic disorder characterized clinically by microcephaly, neurodevelopmental disorders and seizures. Three serine-deficiency syndromes: 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency, 3-phosphoserine phosphatase (3-PSP) deficiency, and phosphoserine aminotransferase deficiency; and a serine transport defect resulting from deficiency of the ASCT1, the main transporter for serine in the central nervous system, have been described.

2. The Symptoms

Serine biosynthesis defects present in a broad phenotypic spectrum that includes, at the severe end, Neu–Laxova syndrome, a lethal multiple congenital anomaly disease, intermediately, infantile serine biosynthesis defects with severe neurological manifestations and growth deficiency, and at the mild end, the childhood disease with intellectual disability. Lack of early signs or symptoms does not exclude the diagnosis.

Neu–Laxova syndrome: is characterized by marked intrauterine growth restriction (IUGR), microcephaly, distinctive facial features, limb and skin defects, and variable brain malformations including lissencephaly, corpus callosum agenesis, and hypoplastic cerebellum and pons. Common distinctive facial features are sloping forehead, hypertelorism, proptotic eyes with absent lids or ectropion, flattened nose, thick everted lips, micrognathia, large ears, and short neck. Limb defects include short limbs, syndactyly with puffiness of hands and feet, contractures with pterygia, overlapping of digits, calcaneovalgus foot deformities, and vertical talus. Skin is usually thin, transparent, edematous, and scaly with yellow subcutaneous tissue. Ichthyosis has been reported in about half of affected individuals. Other congenital anomalies include hypoplastic genitalia, cardiovascular malformations, lung hypoplasia, renal agenesis, cataract, microphthalmia, spina bifida, cleft lip and palate, muscular atrophy, polyhydramnios, small placenta, and short umbilical cord. The majority of affected individuals is stillborn or dies in the immediate neonatal period. It is well established now that Neu–Laxova syndrome is caused by deficiencies of any of the three serine biosynthetic enzymes and represents the severe end of a broad phenotypic spectrum associated with serine biosynthesis defects.

3. Actions to take in case of early diagnosis

  • Babies with a positive genetic test (having 2 mutations or 2 copies of a single mutation in one of the referred genes) should continue breastfeeding. Early treatment is essential in preventing chronic symptoms.
  • Biochemical correlation is essential for confirming diagnosis with decreased concentrations of serine (Ser) and glycine (Gly) in CSF and plasma. Biochemical NBS with tandem mass spectrometry normally doesn’t have low cutoffs for Ser and Gly.
  • SBTD is a lifelong group of diseases that requires lifetime management and regular follow-up with a metabolic physician, a part from a multidisciplinary approach to care.
  • L-serine therapy may be beneficial in preventing or ameliorating symptoms in serine biosynthesis and transport defects, if started before neurological damage occurs.
  • Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

 4. For more information

Orphanet:

Biblio: El-Hattab AW. Serine biosynthesis and transport defects. Mol Genet Metab. 2016;118(3):153-159. PMID: 27161889.