Objective: To describe the phenotypic features of an ethnically homogenous group of patients with Fanconi-Bickel syndrome harboring the p.R310X mutation.Methods: The study group consisted of eight patients from a single Bedouin family with clinically and molecularly diagnosed Fanconi-Bickel syndrome who had been followed at the same tertiary medical center for 8 years or more. All were homozygous for the p.R310X mutation. The medical files were reviewed for presenting signs and symptoms, laboratory and imaging findings, treatment regimens, and disease severity over time.

Hyperargininemia is a rare autosomal recessive disorder of the last step of the urea cycle characterized by a deficiency in liver arginase1. Clinically, it differs from other urea cycle defects by a progressive paraparesis of the lower limbs (spasticity and contractures) with hyperreflexia, neurodevelopmental delay and regression in early childhood. Growth is affected as well. Hyperammonemia is episodic, if present at all. The disease is caused by mutations in the ARG1 gene; there are approximately 20 different known ARG1 mutations with considerable genetic heterogeneity. We describe two Arab siblings with a late diagnosis of hyperargininemia and present the genetic findings in their family. As ARG1 sequencing was unrevealing despite suggestive clinical and laboratory findings, molecular cDNA analysis was performed. The ARG1 expression pattern identified a 125-bp out-of-frame insertion between exons 3 and 4, leading to the addition of 41 amino acids and a premature termination codon TGA at the sixth codon downstream. The insertion originated at intron 3 and was attributable to a novel c.305 + 1323 t > c intronic base change that enabled an enhancement phenomenon. This is the first reported exon-splicing-enhancer mutation in patients with hyperargininemia. The clinical course and genetic findings emphasize the possibility that hyperargininemia causes neurological deterioration in children and the importance of analyzing the expression pattern of the candidate gene when sequencing at the DNA level is unrevealing.

A total of 21 children with clinically and microbiologically proven craniofacial nontuberculous mycobacterial lymphadenitis managed by observation only at a tertiary medical center in 1993-2005 were evaluated for scar parameters at least 2 years after diagnosis. Parents completed a satisfaction questionnaire. Median follow-up time from presentation was 6.8 years (range = 2.3-16.9 years). In all, 18 patients showed scar formation, for a total of 26 scars; 21 scars (81%) had a maximal length of ≤3 cm. Vascularity was normal in 20 scars (77%), and pigmentation was normal in 18 (69%); 21 scars (81%) had a normal to only mildly uneven surface. Although 8 parents (44%) reported that the presence of the scar disturbed them, all responders but one (94%) expressed overall contentment of observation only as a conceivable management alternative. In conclusion, an observation-only approach to craniofacial nontuberculous mycobacterial lymphadenitis is associated with an acceptable outcome and may be an alternative to patients who wish to avoid surgery.