Retrospective survey of urea cycle disorders: Part 2. Neurological outcome in forty‐nine Japanese patients with urea cycle enzymopathies

Abstract

We analyzed neurological data, including DQ or IQ, EEG, and CT scan, in 49 patients with urea cycle enzymopathies, all of whom were included in a retrospective survey from 1978-1988 in Japan. We classified 3 groups depending on age-at-onset: group 1 (0-28 days, N = 11), group 2 (29 days-5 years, N = 31), and group 3 (greater than 5 years, N = 7). The least DQ or IQ score and the highest CT score, representing the most severe brain damage was found in group 1, and the highest DQ or IQ and the least CT score was found in group 3. Intermediate scores of both parameters were found in group 2. There was a negative correlation between these 2 parameters (r = -0.82, P less than 0.01). Abnormal EEG during the attack-free period was predominantly observed in patients with CT abnormalities compared to those with a normal CT scan (P less than 0.01). Approximately 40% of the patients, mostly in groups 2 and 3 (92.8%) had normal findings in all 3 parameters. Thus, the magnitude of developmental abnormalities is clearly related to the degree of brain damage and to the age-at-onset of these diseases.

Ornithine Transcarbamylase Deficiency with Persistent Abnormality in Cerebral Glutamate Metabolism in Adults

“…The time courses of glutamate C4 and C2 and [1][2][3][4][5][6][7][8][9][10][11][12][13] C]-glucose appearing in the brain of one control subject (Fig 3c) and of one OTCD patient (Fig 3d) illustrate the principal differences between OTCD patients and control subjects.…”

“…Investigators in most studies in which 13 C MR spectroscopy is used have determined cycling from isotopic labeling of glutamine and glutamate by using a [1][2][3][4][5][6][7][8][9][10][11][12][13] C]-glucose tracer, which provides the label through neuronal and glial pyruvate dehydrogenase or through glial pyruvate carboxylase. To measure the anaplerotic contribution, 13 C incorporation into glutamate and glutamine in the occipitalparietal region of patients who are awake, we also used an infusion of [2][3][4][5][6][7][8][9][10][11][12][13] C]-glucose, which labels the C2 and C3 positions of glutamine and glutamate exclusively through pyruvate carboxylase.…”

“…he urea cycle disorders (UCDs) are a common group of inborn errors of metabolism (1,2). Syndromes involving deficiencies of five urea cycle enzymes and three cofactors and transporters have been described (3)(4)(5).…”

The ornithine transcarbamylase (OTC) gene: Mutations in 50 Japanese families with OTC deficiency

“…In a group of male patients with neonatal onset (Յ30 days), OTC activity in the liver is often undetectable and they usually die neonatally. Another group, male patients with late onset (>30 days) have mild clinical symptoms and show decreased but detectable OTC activity in the liver Nagata et al, 1991a;Brusilow and Horwich, 1995]. Female heterozygotes have a wide clinical spectrum, ranging from asymptomatic to moderate or severe manifestations.…”

Inborn errors of urea synthesis

“…Children in coma for less than 3 days had a far better outcome than did those in coma for longer periods of time [22). Cognitive outcome also was better in prospectively treated infants with complete defects (mean IQ, 73) and in children with partial defects [45, 54,551.…”