A number sign (#) is used with this entry because of evidence that phosphoserine aminotransferase deficiency (PSATD) is caused by compound heterozygous or homozygous mutation in the PSAT1 gene (610936) on chromosome 9q21.

Deficiency of phosphoserine aminotransferase (PSAT) is characterized biochemically by low plasma and cerebrospinal fluid (CSF) concentrations of serine and glycine and clinically by intractable seizures, acquired microcephaly, hypertonia, and psychomotor retardation. Outcome is poor once the individual becomes symptomatic, but treatment with serine and glycine supplementation from birth can lead to a normal outcome (Hart et al., 2007).

Hart et al. (2007) identified PSAT deficiency in a brother and sister, the children of nonconsanguineous British parents, who showed low concentrations of serine and glycine in plasma and CSF. The index patient was healthy at birth, with head circumference and weight in the 9th percentile. At age 2 weeks he was admitted to the hospital with poor feeding and cyanotic episodes. At age 7 weeks he was experiencing jerking movements and posturing. At age 9 weeks he presented with severe, intractable seizures and slight hypertonia. His head circumference was less than the 0.4th percentile, whereas weight was in the 2nd percentile. His seizures could not be controlled despite multiple-anticonvulsant therapy. Extensive biochemical investigations revealed no abnormalities with the exception of low plasma and CSF concentrations of serine and glycine. Cranial imaging showed generalized atrophy, a hypoplastic cerebellar vermis, and poor white matter development. Treatment with serine begun at 11 weeks of age normalized plasma and CSF concentrations, but the clinical effect was limited. Severe seizure episodes continued, hypertonia worsened, and the patient died at age 7 months. In the proband's younger sister plasma and CSF samples in the neonatal period revealed low concentrations of serine and glycine, and supplementation with serine and glycine was begun in the first 24 hours of life. Her growth and development were normal at 3 years of age, with the exception of an apneic episode at age 2 weeks. Analysis of fibroblasts from the proband revealed phosphoserine aminotransferase activity that was low in comparison to that in controls (approximately 50% decreased), but not sufficiently so to conclude the presence of a deficiency disorder. Hart et al. (2007) also noted that plasma serine and glycine concentrations were only marginally below the reference range in the proband, emphasizing the importance of measuring serine and glycine in CSF as well as plasma.

Glinton et al. (2018) reported a 7-month-old female with PSATD. Fetal MRI at 34 weeks' gestation showed microcephaly, prominent CSF spaces, corpus callosum hypoplasia, and cerebral gyration. Postnatal MRI showed prominent CSF spaces, hypomyelination, severe callosal hypoplasia, and a diffusely simplified gyral pattern with frontal lissencephaly. She had pan-craniosynostosis, failure to thrive, severe feeding difficulties, irritability, and severe developmental delay. Serine and glycine supplementation led to improved weight gain and reduced irritability, but developmental delay was profound.

Debs et al. (2021) reported a woman who had a prenatal history of intrauterine growth retardation and after birth had microcephaly. She required special education and had a clumsy gait. At 13 years of age, she had progressive gait difficulties. She developed limb contractures and hearing loss at 20 years of age. She had dry scaling skin since birth, hair abnormalities including patchy scalp alopecia and trichorrhexis, and nail dystrophy. At 38 years of age, she had bilateral macular lesions, severe spastic dysarthria, distal atrophy and weakness, and contractures of all extremities.

Brassier et al. (2016) reported a boy (patient 2) who had a prenatal history of intrauterine growth retardation and progressive microcephaly. At 1 month of age, he had feeding difficulties and dystonic posturing. Brain MRI at 2.7 years of age showed reduction of white matter volume, atrophy of the vermis, and a hypoplastic corpus callosum. His plasma and CSF serine and glycine were low.

Debs et al. (2021) treated a patient with phosphoserine aminotransferase deficiency with high dose oral L-serine. The patient had improvement in skin manifestations, including ichthyosis, trichorrhexis, and onychodystrophy. She also had resolution of her hypertension and increased alertness.

Brassier et al. (2016) treated a 3-month-old patient with PSATD with oral serine, which resulted in improved spasticity.

In 2 sibs with PSAT deficiency, Hart et al. (2007) identified compound heterozygosity for mutations in the PSAT1 gene: a frameshift mutation on the paternal allele (G107del; 610936.0001) and a missense mutation on the maternal allele (D100A; 610936.0002). Expression studies of the D100A mutant protein revealed a V(max) of only 15% of that of the wildtype protein.

By whole-sequencing in a 7-month-old female with PSAT deficiency, Glinton et al. (2018) identified compound heterozygous mutations in the PSAT1 gene (c.432delA, 610936.0006 and A15V, 610936.0007). Plasma amino acids showed low serine and low/normal glycine, and CSF amino acids showed low serine and normal glycine. Analysis of the newborn screening blood spot of this patient showed low serine with a Z-score of -2.4.

Debs et al. (2021) identified compound heterozygous mutations (T156M, 610936.0008 and A15P, 610936.0009) in the PSAT1 gene in a woman with PSATD. The mutations were identified by whole-exome sequencing.

In a Turkish boy, born of consanguineous parents, with PSATD, Brassier et al. (2016) identified homozygosity for a S43R mutation (610936.0010) mutation in the PSAT1 gene, Purified PSAT1 with the S43R mutation had a decreased Vmax and increased Km compared to wildtype protein.