BackgroundMutations in the PIGV, PIGO, PIGL, PIGY, PGAP2, PGAP3, and PIGW genes have recently been reported to cause hyperphosphatasia accompanied by mental retardation syndrome (HPMRS); the latter is an autosomal-recessive neurological disorder typically characterised by recurrent seizures, intellectual disability, and distinct facial features. Here, we report an extremely rare case of a Chinese boy with compound heterozygous PIGW mutations who suffers from severe pneumonia, mental retardation, and epilepsy.Case presentationA 70-day-old boy presented with fever and cough over 20days in duration at the time of admission. At the age of 6months, unusual facial features were apparent, and seizures were clinically observed, accompanied by obvious cognitive delay. Next-generation sequencing identified novel PIGW c.178G>A and c.462A>T mutations, confirmed by Sanger sequencing.ConclusionsMutations in the PIGW gene in infants can cause various symptoms and multiple anomalies. Next-generation sequencing efficiently detects such mutations. The compound PIGW mutations that we describe expand the genotype/phenotype spectrum of HPMRS and may aid in clinical treatment.