Secondary Cystathioninuria

Abstract

Increased urinary excretion of cystathionine has been reported in 6 patients and was associated in 5 of them with mental retardation. This patient group is interpreted as having an inborn error of metabolism due to a disturbance in the metabolic breakdown of cystathionine (primary cystathioninuria) 1(4). Several reports of increased urinary excretion of cystathionine in children in combination with various diseases, eg. pyridoxine deficiency, neuroblastoma galactosaemia and hepatoblastoma have been published (for review of such cases of secondary cystathioninuria see Shaw et al.)(1 1).The purpose of the present investigation was to study the frequency of cystathioninuria in larger groups of hospitalized children. MATERIAL AND METHODSThe material examined consists of 230 children in whom the urinary aminoacid pattern had been requested on the ground of suspected metabolic disorders, especially in patients with malformation, mental retardation or convulsions. The patients were all hospitalized a t the paediatric department, General Hospital, Malmo. The urine samples from patients had been stored at +4" and were analysed within 3 days.The urinary a-amino nitrogen were measured as described by Khachadurian ef al. (8). The urinary aminoacids were separated by high-voltage paper electrophoresis combined with paper chromatography (13). Samples of urine, which contained 5 mg of creatinine, were initially passed through a 3 cm column of Zeo-Karb 225 resin to remove urea and to reduce volume (2). The concentrated aminoacid solu-12 --692889 Aeta P a d i a t Scand 58 tion corresponding to 75 p g creatinine was then applicated to Whatman No. 3 M M paper and separated by electrophoresis with formateacetic acid, pH = 1.2. The voltage gradient was 40 V per cm; running time 90 minutes. Three parallel runs were performed on the same paper. After electrophoresis two strips were cut away from the large sheet of paper and were stained with ninhydrin (12) iodine-platinate (12) respectively. The last reagent was used for localizing the sulphur-containing aminoacids. The third strip was used for chromatography in the second dimension (n-butanol, acetic acid, water, 12 : 3 : 5 v/v) over night. Under the electrophoretic conditions described methionine and cystine migrated together but cystathionine had a greater migration rate towards the cathode, The only sulphur-containing aminoacid which had the same migration rate as cystathionine under these conditions was homocystine. Chromatography in the second dimension separates these two aminoacids as well as methionine and cystine. The following Rf-values were found: Cystine = 0,08; methionine = 032; homocystine 0,18; and cystathionine = 0,lO.Homocystine was never found. The sensitivity of the iodineplatinate reagent allows detection of cystathionine in concentrations as low as 0.2 p g per spot. The recovery of cystathionine by this method was about 90% thus the lower limit of detection was about 2 mg cystathionine per g creatinine.When a sulphur-positive aminoacid in the area of cystathionine...

Occurrence of secondary cystathioninuria in children with inherited metabolic disorders, liver diseases, neoplasms, cystic fibrosis and celiac disease

“…With regard to leukemia and tumors, our results are in accord with observations made by Geiser and Efron [4]. However, we expected a more frequent occurrence of secondary cystathioninuria in patients with liver diseases and hereditary metabolic disorders in view of the published data [1,8,10,11].…”

“…The same is true for increased transaminase activities (2/7~29% vs. 10/37 ~ 27%). This agrees with the results of other authors [1,8,11]. Thus, it may be concluded that hepatomegaly and increased transaminases are frequent findings in patients with secondary cystathioninuria, but not vice versa.…”

“…However, in these cases disturbed metabolism of metnionine due to liver damage by the tumor or metastases may also be partially responsible for the cystathioninuria. This is supported by the fact that liver metabolism in some patients with cystathionin-uria s e c o n d a r y to diseases o t h e r t h a n n e u r o b l a s t o m a a n d h e p a t o m a is d i s t u r b e d by the p r i m a r y disease [1,8,10,11].…”

“…Secondary cystathioninuria has been reported in patients with neuroblastoma [4,5,7,12], hepatoma [6,10,13], hepatitis [11], biliary atresia [1], liver cirrhosis [1,8], galactosemia [8,10], tyrosinosis [10], vitamin D intoxication [1], non-ketotic hyperglycinemia [1], reactive granulocytopoesis of the liver [1] and vitamin B6 deficiency [3,9,11]. I n patients with glycogenosis, type 4 [8,10], maple syrup urine disease [10] and congenital portal vein obstruction [10] it has been noticed shortly before death.…”