The pancreatic beta cell fraction in children with errors of amino acid metabolism.

Blocks of pancreas were obtained from the following cases of errors of amino acid metabolism: eight cystinosis, eight tyrosinosis, five phenylketonuria, three hypermethioninemia, two hyperprolinemia and two maple syrup urine disease. Blocks were also obtained from four cases of homocystinuria and 72 control patients of the same age range who had died from a variety of conditions believed not to affect the pancreas. Sections were cut from each pancreatic block and stained with haematoxylin or for insulin and pancreatic polypeptide (PP) by the immunoperoxidase method. Measurements were performed separately in the PP rich and the PP poor regions of all sections. The fractional surface area of section occupied by insulin stained cells (%) and the cellular density (nuclei/100 microgram2) of each specimen were estimated. The beta cell fractional area in the PP poor region of the experimental cases was plotted against the logarithm of gestational age and compared to a reference grid of the 10th, 50th and 90th centile estimates of the control cases (Fig. 1). The distribution of results from the cases of tyrosinosis, phenylketonuria and cystinosis were skewed positively; four of eight tyrosinosis and three of five phenylketonuria cases lying above the 90th centile (P less than 0.001). The beta cell fractional area of the cystinosis cases was also significantly increased (Table 1, P less than 0.05). The results from the cases dying from maple syrup urine disease, hyperprolinemia, hypermethioninemia or homocystinuria were distributed as might be expected to occur by chance.