VARIABLE PRESENTATION OF PRIMARY HYPEROXALURIA TYPE-1 IN 2 PATIENTS HOMOZYGOUS FOR A NOVEL COMBINED DELETION AND INSERTION MUTATION IN EXON-8 OF THE AGXT GENE

Two unrelated patients of Pakistani origin presented with primary hype roxaluria type 1 (PH1) at 4 months and 3 years of age, respectively, W hile the younger patient failed to thrive and suffered from early rena l failure, the older one showed a relatively benign history with uroli thiasis as the main feature of the disease, In both patients the diagn osis was confirmed by assessment of alanine:glyoxylate aminotransferas e catalytic and immunoreactivity in liver biopsy specimens, The underl ying genetic defect was found to be a combined deletion and insertion in exon 8 which alters the reading frame of the protein, The nucleotid e change introduces a Stu1 restriction site which facilitated typing o f additional family members, Both patients and a further affected brot her were homozygous for this mutation, while their parents were hetero zygous for it. This mutation is the first deletion/insertion identifie d in PH1. Although rare in our PH1 patient cohort (2.5% of alleles), t he finding of 2 homozygous apparently unrelated individuals of the sam e ethnic origin suggests that it may prove worthwhile to screen other Asian patients for this mutation. These PH1 cases present further evid ence that factors other than genotype contribute significantly to the clinical presentation and severity of PH1.