First case of Currarino syndrome and trimethylaminuria: two rare diseases for a complex clinical presentation

Background: Firstly described in 1981, Currarino syndrome is a rare condition characterized by a triad of three congenital malformations: partial sacral agenesis, presacral mass and anorectal malformation; however, often only one or two anomalies are present. The main symptom is chronic constipation. Mutations in MNX1 gene are the causes of familial cases and of about 30% of sporadic ones; MNX1 encodes for a transcription factor that regulates expression of genes involved in organs development. Exon 1 is the mutations hotspot and a polymorphic [(GCC)N] trait is contained within. If [(GCC)N] number’s repeats may contribute to CS development is still unknown. Trimethylaminuria is a metabolic disorder characterized by failure of trimethylamine N-oxidation due to deficit FMO3 enzyme. Odorous trimethylamine is converted in the non-odorous oxigenate form by FMO3 then, this is excreted mainly in the urine. FMO3 mutations and several polymorphisms leads to a reduced enzymatic activity resulting in excretion into body fluids of trimethylamine with consequent emission of unpleasant odor. Methods: Here we describe the first case of 64-year-old female presenting with fistulous sacral-coccygeal congenital malformation, anorectal stenosis. She complained of a long-standing fish odor affecting her sweat and breath. Events of halitosis, high transaminases levels, stomatitis and alopecia were also reported. CS was already diagnosed in her family member while Trimethylaminuria was suspected. Molecular analysis by direct sequencing was performed both for MNX1 and for FMO3 genes. Results: a known CS causative mutation was detected; while in FMO3 gene three polymorphisms were found, notoriously associated with a reduced enzymatic activity. Conclusions: Molecular analysis of MNX1 gene confirmed CS diagnosis; possible roles of [(GCC)N] repeats in CS development or in phenotype’s severity were also considered. A condition of transient trimethylaminuria was, instead, hypothesized.