Long-term use of carglumic acid in methylmalonic aciduria, propionic aciduria and isovaleric aciduria in Italy: a qualitative survey.

OBJECTIVE: Organic acidurias (OAs) are a group of rare metabolic disorders that disrupt the regular amino acid metabolism. OAs are characterized by recurrent episodes of acidemia, ketonuria and hyperammonemia which can result in brain/liver damage and renal failure, and despite the life-long protein-restricted diet, impaired growth and long-term complications can occur. Consequently, a long-term management of OAs patients is required, aimed principally at reducing the frequency and duration of metabolic decompensation/hyperammonemia episodes. Nevertheless, unlike the acute phase, evidence on the chronic management of OAs patients is less consolidated. SUBJECTS AND METHODS: To expand the knowledge on this field, 13 Italian referral centers for the management of OAs were involved in a survey focused on the long-term use of carglumic acid (Carbaglu®, Recordati Rare Diseases). RESULTS: Participating centers reported a reduction between 69% and 81% in the annual number of metabolic decompensations with the chronic use of carglumic acid and an improvement in protein intake. Most centers reported no difficulty using carglumic acid as a long-term therapy, along with a great compliance. CONCLUSIONS: Taken together, obtained data align with the available literature and support a positive clinical experience with the long-term carglumic acid administration. Additional studies aimed at better defining a proper dosage for the chronic administration of carglumic acid and the clinical and biochemical characteristics of patients treated chronically are needed. In addition, the potential impact of this treatment regimen on the neurological development and growth of patients should be elucidated.

A novel frame-shift deletion causing analbuminaemia in an Italian paediatric patient.

BACKGROUND: Analbuminaemia (OMIM #103600) is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. The trait is caused by a variety of mutations within the albumin gene. DESIGN: We report here the clinical and molecular characterization of a new case of congenital analbuminaemia in a 4-year-old Italian girl diagnosed on the basis of the low level of circulating albumin (= 10.0 g L(-1)). The albumin gene was screened by single-strand conformation polymorphism and heteroduplex analysis and the mutated region submitted to DNA sequencing. RESULTS: The proband was found to be homozygous, and both parents heterozygous, for a novel deletion in exon 8 (c.920delT). The subsequent frame-shift should have given rise to a putative polypeptide chain of 304 amino acid residues, which we could not identify in the proband's serum. CONCLUSIONS: A novel analbuminaemia causing mutation was identified and characterized at the clinical level in a child. The molecular diagnosis of the trait is based on the rapid localization of the mutation within the albumin gene by single-strand conformation polymorphism and heteroduplex analysis, followed by DNA sequencing of the mutated region.