Citrullinemia

Abstract

the second known case of citrullinemia. The child was the product of unwed and supposedly unrelated parents. During the first 5\m=1/2\months of life her foster mother felt that her growth and development were normal except for a severe, persistent diaper rash. At 6 weeks of age she smiled and at 3\ m=1/ 2\ months she began to roll over. Beginning at this time she suffered periods of non\x=req-\ projectile vomiting which lasted for several days at a time. She became less interested in her surroundings, and more irritable. Despite dietary changes her illness progressed and she was admitted at 8 months of age to the Children's Hospital of Philadelphia with hematemises, hematuria, and purpura.Physical examination at the time of admission revealed a responsive but somewhat irritable child who fell in the tenth percentile for both height and weight. The spleen and liver were not palpable. The child was placed on a baby-soft diet but demonstrated no improvement in vomiting or irritability. On the 13th day she had a grand mal seizure that was followed by several hours of unresponsiveness. It was felt retrospectively that this represented a cerebrovascular accident.Laboratory data revealed that the child had a PTC (factor IX) deficiency with prolonged prothrombin times of less than 15% normal. The SGOT was 1,280 units, albumen-globulin ratio 2.3/1/4 gm/ 100 cc, and BUN 6 mg/100 cc. The rest of the chemistries were within normal ranges.X-ray examination of the upper gastroin¬ testinal tract, abdomen, skull, and chest showed normal results except for marked osteoporosis, which was felt to have a nutri¬ tional basis. Two-way urinary chromatogram screen revealed an abnormal amino acid that was shown by Dr. Mary Efron to be citrulline.The child was placed on a low-protein diet (0.6 gm/lb/day as S-14 [Wyeth] ) and trans¬ ferred to the clinical research center for further investigation. Within two weeks of being placed on the low-protein diet, evidence of defective protein metabolism was reversed, ie, the albumen-globulin ratio returned to normal, 3.6/2.6 gm/100 cc, SGOT had fallen to 180 units, and cerebrospinal fluid protein had risen from 9 to 20 mg/100 cc. The marked osteoporsis which was noted at ad¬ mission was reversed several months later onx-ray films, as seen by formation of normally calcified bone. In addition, the PTC de¬ ficiency quickly reverted to normal, although vitamin was also administered.Once the diagnosis of citrullinemia was established, the ammonia, urea, and citrulline levels were monitored for evaluating therapy.Blood ammonia nitrogen was measured by the Seligson method and was initially nor¬ mal. Unfortunately, this was a fasting speci¬ men. During the first four months when dietary intake was restricted to S-14, post¬ prandial blood ammonia values ranged above

Citrullinaemia with Rapidly Fatal Neonatal Course

“…The citrulline concentration in blood, CSF, and urine was considerably higher, and the derangement of the amino acidi pattern of blood was much greater in our patient. McMurray et al (1963) and Morrow (1967) found, apart from the very high citrulline levels, only an increase of glutamic acid and methionine and a decrease of ornithine in the serum of their patients. In our patient, however, the concentration of most amino acids was greatly increased (Table I).…”

“…Only 3 cases have been reported previously (McMurray et al, 1962;1963;McMurray et al, 1964;Mohyuddin, Rathbun, and McMurray, 1967;Morrow, Barness, and Efron, 1967;Morrow, 1967;Wick, Brechbuhler, and Girard, 1970). The normal synthesis of argininosuccinic acid is blocked in this disease due to a deficiency of argininosuccinate synthetase, which has been demonstrated in liver cells and fibroblasts (McMurray et al, 1964;Tedesco and Mellman, 1967).…”

Variants of citrullinaemia.

“…The patients can be divided into two groups according to the severity of the disease. In 3 cases (McMurray et al, 1963;Morrow, 1967;Vidailhet et al, 1971) the disease was detected in early childhood between 7 and 18 months of age. The prominent features were severe mental retardation and spells of vomiting.…”

Video characterization of flume patterns of inhalation aerosols

“…When the alveolated regions of the lungs are the desired site of therapeutic action, the size is limited to 1-5 pm in diameter. The deposition of particles in the 1-10-pm aerodynamic diameter range is governed by inertial impaction and gravitational settling (14).…”