• PRODH
• deletion
• hyperprolinaemia
• mental retardation

Since the original reports of hyperprolinaemia by Scriver et al¹ and Shafer et al,² two types of this rare metabolic disorder have been biochemically characterised³: type I (MIM 239500) results from the defect of the enzyme proline dehydrogenase (oxidase), which ensures the conversion of proline into Δ-1-pyrroline-5-carboxylate (P5C), the first step in the conversion from proline to glutamate,⁴ and type II (MIM 239510) is the result of a defect of the P5C dehydrogenase/aldehyde dehydrogenase 4 enzyme and P5C is excreted in the urine.⁵

The phenotype of type II hyperprolinaemia is characterised by neurological manifestations including seizures and mental retardation.^3,6,7 Although type I hyperprolinaemia was originally described in a kindred with a familial nephropathy,^1,2 the renal disease was subsequently shown to be coincidental and type I hyperprolinaemia has been considered to be a benign disorder which can be asymptomatic.³ Nevertheless, two studies have reported severe neurological manifestations (mental retardation, epilepsy) in two male children with type I hyperprolinaemia.^8,9 While mutations of the ALDH4A1 gene, located on chromosome 1p36, have been identified in families with type II hyperprolinaemia,¹⁰ the molecular basis of type I hyperprolinaemia has not been characterised until recently. We have recently identified in schizophrenic patients a heterozygous deletion and mutations of the PRODH gene, located on 22q11, which were associated with moderate hyperprolinaemia. We …