Hyperprolinemia Type IA: Benign Metabolic Anomaly or a Trigger for Brain Dysfunction?

Abstract Objective: Hyperprolinemia type I (HPI) is a rare and inherited autosomal recessive disorder caused by proline oxidase deficiency. Hyperprolinemia type 1 is biochemically defined as high plasma proline levels without urinary ?-1-pyrroline-5-carboxylate excretion. Hyperprolinemia type 1 has been considered a benign metabolic disorder, but a relationship with neurological disorders has recently been suggested. Study Design: We retrospectively analyzed plasma amino acid values obtained by amino acid analysis from 10 030 children admitted for neurological reasons during the years 1996 to 2010 at the Regional Sicilian Centre for Metabolic Diseases. Patients with proline levels above the normal range of 129 to 245 ?M were identified. Results: Only 2 children showed high levels of proline (450-480 ?M and 380-470 ?M, respectively), but their disorders (tubercular neuroencephalitis and progressive mitochondrial encephalopathy) did not seem to be related to hyperprolinemia as a causative factor. Conclusion: The question of HPI as benign metabolic anomaly or as a direct cause of brain damage is still open. Since HPI is rare, other observations on this regard are necessary.

Isolated liver disease in a patient with a CFTR genotype F508del/12TG-5T and 470MV: A new face of an old disease.

Today the knowledge of genotype-phenotype correlation in cystic fibrosis is enriched by the growing discoveries of new mutations of the CFTR gene. Although the combination of two severe mutations usually leads to the classic disease (pulmonary and pancreatic insufficiency, sterility, nasal polyposis), the presence of a complex genotype characterized by severe and milder mutations or polymorphism can cause a hidden disease, which is often asymptomatic at early ages. We report on a case of a 15 years old boy, in whom the only clinical signs of CF were chronic hypertransaminasemia and hyperbilirubinemia, and in whom it was demonstrated the presence of the mutations F508del associated with TG11-9T-470M in one allele and TG12-5T-470V in the other allele. Although a clear genotype-phenotype correlation for liver disease is still missing for CF patients, it is possible to state that this isolated clinical presentation could represent an unusual phenotype of CF, related to a complex genotype characterized by a severe mutation and one (or more) polymorphism.