No abstract

Extractscribed by Jellum e t al. (7) in an adult male who suffered from metabolic acidosis and neurologic symptoms such as mental Two sisters, One a neonate and the other years of age, retardation, spastic tetraparesis, ataxia, and intentional tremor. were found to suffer from pyroglutamic aciduria (5-oxoproWe have recently described a young girl who also had linuria). They had a chronic metabolic acidosis and required pyroglutamic aciduria and chronic metabolic acidosis but no with their parents, both excreted detectable neurologic damage (6). This patient was studied at large quantites of L-pyroglutamate in the urine.the age of 14 months, when her daily excretion of No ~~r o g l u t a m a t e could be demonstrated in aurine sample ~-~~~~~l~t~~~t in urine amounted to 50 mmol and her blood obtained from the pregnant mother at 30 weeks of gestation. plasma concentration was 4.5 mM. Pyroglutamate turnover Pyroglutamate was, however, detected in amniotic fluid and cord blood plasma as well as in urine from the neonate studies under steady state conditions showed that approxicollected during the first few hours after birth. Metabolic mately 75% of the amount synthesized was metabolized by acidosis developed during the 1st day of life and bicarbonate the patient. The level of 5-oxoprolinase in the patient's therapy was started. The patient also showed a moderate leukocytes was be hyperbilirubinemia but no further c o m p~~c a t~o n s were enIndependent studies by Eldjarn and coworkers (2)(3)(4)(5)7,16) countered in the neonatal period. on their adult patient have also failed to reveal the primary ~h~ 3-year-old girl had a daily excretion of pyroglutamate in defect in pyroglutamic aciduria. The daily excretion of urine corresponding to 195 mmo1/1.73 rn2, i.e., identical with pyr0glutamate in urine was 270 mmol (4, 7)that found at 14 months of age. ~h~ excretion showed no and was not affected significantly by variations in the dietary correlation with feeding or physical activity. The concentra-Protein intake (2). After an intravenous dose of (14 c )~~r o~l utions of pyroglutamate in plasma and cerebrospinal fluid were tamate the patient expired considerably less 14c02 than a 2.2 m~ and 1.3 m~, respectively. she had no evidence of a normal control subject, and this was taken as evidence of a disturbed renal transport of a-amino acids. Her psychologic block in the patient's capacity to metabolize ~~r o~l u t a m a t e and somatic development was normal, and she had no signs of (2). However, the patient had a normal level of 5-Oxoprolinase neurologic damage. in cultured fibroblasts (16) and subsequent studies have Both patients presented evidence of increased hemolysis and revealed evidence of an increased production of ~~r o~l u t a m a t e their levels of glutathione in erythrocytes were markedly ( 3 3 4). decreased, which indicated a defect in glutathione metabolism.The metabolic role of pyroglutamate has not been settled. Its involvement in the metabolism of glutathione has been Speculation proposed (14). A model for...