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The severe form of type I hyperprolinaemia results from homozygous inactivation of the PRODH gene
  1. H Jacquet1,
  2. J Berthelot2,
  3. C Bonnemains2,
  4. G Simard3,
  5. P Saugier-Veber1,4,
  6. G Raux1,
  7. D Campion1,
  8. D Bonneau2,
  9. T Frebourg1,4
  1. 1INSERM EMI 9906 - IFRMP, Faculty of Medicine, Rouen, France
  2. 2Department of Genetics, CHU d’Angers, France
  3. 3Department of Biochemistry, CHU d’Angers, France
  4. 4Department of Genetics, CHU de Rouen, France
  1. Correspondence to:
 Dr T Frebourg, INSERM EMI 9906 - IFRMP, Faculty of Medicine, Rouen, France;

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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 …

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