Argininemia, Hyperornithinemia, and 3-Hydroxyisovaleric Aciduria

A 50-year-old man with long-standing Crohn disease underwent metabolic investigation as part of evaluation for subacute cognitive decline and confusional state. An infected ulcer present on his left foot for several months was suspected to be pyoderma gangrenosum. Routine biochemistry results including plasma lactate and ammonia were within reference limits. Plasma amino acid examination (high-performance liquid chromatography) on 2 occasions revealed increased arginine at 309 and 377 (reference interval, 15–160) μmol/L and ornithine at 210 and 361 (30–150) μmol/L, while all other amino acids including citrulline and glutamine were within reference limits. Urine organic acid examination (Fig. 1) revealed massively increased excretion of 3-hydroxyisovaleric acid (3-OH-IVA)5 with an otherwise normal profile. Fig. 1. Urine organic acid chromatogram (by GC-MS). Urine organic acids were extracted into ethyl acetate/ether, converted to trimethylsilyl derivatives, and analyzed on an Agilent GC 7890A/MS 5975 system equipped with an Agilent HP-5MS (30 m, 0.25 mm × 0.25 μm) column. Internal standards: 2-phenylbutyric, tropic acid, and margaric acid. Increased arginine is a feature of the urea cycle disorder arginase deficiency, but ornithine, the …