RESUMO
Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations of the VPS33B encoding the vacuolar protein sorting 33B (VPS33B), which is involved in the intracellular protein sorting and vesicular trafficking. We report a rare case of ARC syndrome without arthrogryposis caused by a novel mutation of VPS33B. A female patient of Greek origin presented on the 14th day of life with renal tubular acidosis, Fanconi syndrome, nephrogenic diabetes insipidus, and cholestasis with normal gamma-glutamyl transpeptidase, without arthrogryposis and dysmorphic features. She was born to apparently healthy, nonconsanguineous parents. Additional features included dry and scaling skin, generalized hypotonia, hypoplastic corpus callosum, neurodevelopmental delay, failure to thrive, short stature, recurrent febrile episodes with and without infections, and gastrointestinal bleeding. DNA testing revealed that the patient was homozygous for the novel c.1098_1099delTG (p.Glu367Alafs∗17) mutation of exon 14 of VPS33B gene (NM_018668) on chromosome 15q26.1, leading to a nonsense frameshift variant of VPS33B with premature termination of translation. Her parents were heterozygous for the same VPS33B mutation. The prognosis was predictably poor in the context of the intractable polyuria necessitating long-term parenteral fluid administration via indwelling central catheter leading to catheter-related sepsis, to which she eventually succumbed at the age of 7 months. This is the first published VPS33B mutation in an ARC patient of Greek origin. The current case adds to the spectrum of ARC-associated VPS33B mutations and provides evidence supporting the existence of incomplete ARC phenotype. Increased awareness and early genetic testing for ARC are suggested in cases with isolated cholestasis and/or renal tubular dysfunction, even in the absence of arthrogryposis.
RESUMO
BACKGROUND: Controversy exists as to whether the outcome of vesicoureteral reflux (VUR) can be prognosticated by direct radionuclide cystography (DRC). OBJECTIVE: To correlate the quantitative data obtained by DRC with disease outcome in infants with VUR and positive DRC 1 year after diagnosis. MATERIALS AND METHODS: The medical records of 109 children with known primary VUR diagnosed during the first year of life were studied retrospectively. One year after diagnosis all patients underwent DRC. Children with a positive first DRC were followed up for the next 36 months. Fisher's exact test was used to calculate the statistical significance of differences in the number of ureters with resolved reflux, as related to quantitative data obtained during the first DRC. RESULTS: The first DRC, performed 1 year after the initial diagnosis, was positive in 49 children (26 with bilateral reflux). Quantitative data derived from this first examination could not establish any prognostic value for a refluxing volume of <2% of the total vesical volume or a reflux at a bladder volume of more than 60% of total bladder capacity. When this limit was lowered to 45%, a statistically significant difference was found ( P=0.046). Moreover, when a bladder pressure at the time of reflux of more than 20 cm H(2)O was set as a criterion, an extremely significant probability value was calculated ( P=0.0009). CONCLUSIONS: VUR occurring at a bladder pressure of less than 20 cm H(2)O and a filling volume of less than 45% of the total bladder volume indicate a low probability for VUR resolution within the subsequent 36 months, in infants with known reflux.