5-oxoprolinuria: biochemical observations and case report.

We have studied a patient with 5-oxoprolinuria who presented with hemolysis and metabolic acidosis as a neonate; he has had normal growth and development to one year of age. Compensated hemolytic anemia persists, and he requires alkalinizing agents for correction of acidosis. Biochemical studies have confirmed that a deficiency of glutathione synthetase is responsible for the 5-oxoprolinuria. Genetic heterogeneity was apparent on comparative study of glutathione synthetase kinetics in cells from two patients with this disorder. The consequences of the deficiency of glutathione synthetase, decreased intracellular glutathione, and overproduction of 5-oxoproline are discussed with reference to the possible cellular roles of these compounds.

Endocrine studies in cystinosis: compensated primary hypothyroidism.

Children with nephropathic cystinosis exhibit marked growth retardation. Improved medical management and renal transplantation have increased their life expectancy beyond the second decade. We have studied endocrine function in seven patients with cystinosis and reviewed autopsy findings of four patients and medical records of 24 others. One 10-year-old boy was overtly hypothyroid. The six other patients had normal studies of peripheral thyroid function but two had borderline and two had frankly elevated serum TSH levels. Stimulation tests of cortisol and growth hormone secretion and basal levels of serum NSILA-s were normal. Postmortem histology of the thyroid glands revealed extensive destruction and infiltration of the epithelium with cystine crystals. Despite the presence of cystine crystals in other endocrine tissues, there was no destruction of epithelium in glands other than in the thyroid. We conclude that in nephropathic cystinosis "compensated" primary hypothyroidism occurs frequently and early and may be diagnosed by measurement of serum TSH concentrations.