Phosphoserine Phosphatase Deficiency

A number sign (#) is used with this entry because of evidence that phosphoserine phosphatase deficiency (PSPHD) is caused by homozygous or compound heterozygous mutation in the PSPH gene (172480) on chromosome 7p11.

Clinical Features

Jaeken et al. (1997) described a Belgian patient with phosphoserine phosphatase deficiency. The affected boy had pre- and postnatal growth retardation, moderate psychomotor retardation, and facial features suggestive of Williams syndrome (194050). Phosphoserine phosphatase activity in lymphoblasts and fibroblasts was reduced to 25% of normal values. Treatment with oral serine led to normalization of serine levels and some improvement in head growth (Jaeken et al., 1997).

Vincent et al. (2015) reported a large highly consanguineous Pakistani family in which 7 individuals had delayed development from infancy and moderate to profound intellectual disability. All developed tonic-clonic or petit mal seizures at some point in childhood, and all had hypertonia resulting in motor difficulties. One patient had microcephaly and 1 had brain atrophy apparent on MRI. Plasma serine and glycine levels were decreased in 2 patients tested.

Inheritance

The transmission pattern of PSPHD in the family reported by Vincent et al. (2015) was consistent with autosomal recessive inheritance.

Molecular Genetics

In the patient with phosphoserine phosphatase deficiency reported by Jaeken et al. (1997), Veiga-da-Cunha et al. (2004) identified compound heterozygosity for 2 mutations in the PSPH gene (172480.0001; 172480.0002). They noted that the PSPH gene is separated from the elastin gene (130160), one of several genes implicated in Williams syndrome, by 16.5 Mbp. The authors concluded there was no link between the 2 disorders in this patient.

In affected members of a consanguineous Pakistani family with PSPHD, Vincent et al. (2015) identified a homozygous missense mutation in the PSPH gene (A35T; 172480.0004). The mutation, which was found by homozygosity mapping and Sanger sequencing of candidate genes, segregated with the disorder in the family. Enzymatic analysis showed that the mutant protein had approximately 10-fold lower activity than wildtype.