30-year follow-up of a patient with classic citrullinemia.

Citrullinemia is a urea cycle defect requiring long-term care with nutritional and pharmacological management. Despite treatment, morbidity and mortality of this disease remain high, and long-term complications include mild to profound mental retardation, seizures, and growth deficiency. We report a 31-year old woman with classic, neonatal-onset citrullinemia who developed progressive hypertrophic cardiomyopathy and cataracts, neither of which has been recognized previously as a complication of the disease or a consequence of long-term drug treatment.

Management of ornithine transcarbamylase deficiency in pregnancy.

Ornithine transcarbamylase (OTC) deficiency is the most common enzymatic deficiency in the urea cycle. In catabolic states, such as the intrapartum and immediate postpartum periods, hyperammonemic comas with permanent neurological damage and death can develop. We report six cases of OTC deficiency during pregnancy managed at our institution and review the literature on OTC deficiency during pregnancy. Using the patient database from our Metabolic Clinic, pregnant OTC deficiency carriers were identified. The antenatal, intrapartum, and postpartum periods were analyzed. Corresponding literature was reviewed and an extensive multidisciplinary management plan developed. All six pregnant women had favorable outcomes. No hyperammonemic episodes occurred, and intensive care unit admissions and hemodialysis were not required. Although risk to women with OTC deficiency during the intra- and postpartum period exists, multidisciplinary management and a coherent plan usually result in successful labor, delivery, and postpartum. A comprehensive plan for patients who develop hyperammonemia is recommended.

Epimerase-deficiency galactosemia is not a binary condition.

Epimerase-deficiency galactosemia results from the impairment of UDP-galactose 4'-epimerase (GALE), the third enzyme in the Leloir pathway of galactose metabolism. Originally identified as a clinically benign "peripheral" condition with enzyme impairment restricted to circulating blood cells, GALE deficiency was later demonstrated also to exist in a rare but clinically severe "generalized" form, with enzyme impairment affecting a range of tissues. Isolated cases of clinically and/or biochemically intermediate cases of epimerase deficiency have also been reported. We report here studies of 10 patients who, in the neonatal period, received the diagnosis of hemolysate epimerase deficiency. We have characterized these patients with regard to three parameters: (1) GALE activity in transformed lymphoblasts, representing a "nonperipheral" tissue, (2) metabolic sensitivity of those lymphoblasts to galactose challenge in culture, and (3) evidence of normal versus abnormal galactose metabolism in the patients themselves. Our results demonstrate two important points. First, whereas some of the patients studied exhibited near-normal levels of GALE activity in lymphoblasts, consistent with a diagnosis of peripheral epimerase deficiency, many did not. We detected a spectrum of GALE activity levels ranging from 15%-64% of control levels, demonstrating that epimerase deficiency is not a binary condition; it is a continuum disorder. Second, lymphoblasts demonstrating the most severe reduction in GALE activity also demonstrated abnormal metabolite levels in the presence of external galactose and, in some cases, also in the absence of galactose. These abnormalities included elevated galactose-1P, elevated UDP-galactose, and deficient UDP-glucose. Moreover, some of the patients themselves also demonstrated metabolic abnormalities, both on and off galactose-restricted diet. Long-term follow-up studies of these and other patients will be required to elucidate the clinical significance of these biochemical abnormalities and the potential impact of dietary intervention on outcome.