A novel compound heterozygous mutation in the arginase-1 gene identified in a Chinese patient with argininemia: A case report.

INTRODUCTION: Arginineemia, also known as arginase deficiency, is a rare autosomal recessive metabolic disease. The diagnosis sometimes may be delayed due to atypical clinical manifestations. Confirmation of arginineemia depends on genetic testing. PATIENT CONCERNS: We reported a Chinese male child presenting with hyperargininemia and progressive spastic diplegia, who has a novel compound heterozygous mutation in the arginase-1 (ARG1) gene (c.263-266delAGAA, p.K88Rfs45;c.674T>C,p.L216P), respectively, coming from his mother and father. DIAGNOSIS: The patient was diagnosed with argininemia with a novel compound homozygous mutation of the ARG1 gene at the age of 12 years. INTERVENTIONS: The patient had a low-protein diet (0.8 g/kg/day). Baclofen, eperisone hydrochloride, botulinum toxin, and rehabilitation training were used to improve his spastic diplegia symptoms for 3 months. OUTCOMES: The patient's blood arginine was still high after 3 months' low-protein diet. His spastic diplegia symptoms had not aggravated after 3 months' treatment. CONCLUSIONS: Argininemia should be considered in a patient with slowly progressive neurologic manifestations, especially spastic diplegia. This case also suggests that tandem mass spectrometry should be used as an effective tool in the validity of neonatal screening for early diagnosis.

Label-free quantitative urinary proteomics identifies the arginase pathway as a new player in congenital obstructive nephropathy.

Obstructive nephropathy is a frequently encountered situation in newborns. In previous studies, the urinary peptidome has been analyzed for the identification of clinically useful biomarkers of obstructive nephropathy. However, the urinary proteome has not been explored yet and should allow additional insight into the pathophysiology of the disease. We have analyzed the urinary proteome of newborns (n = 5/group) with obstructive nephropathy using label free quantitative nanoLC-MS/MS allowing the identification and quantification of 970 urinary proteins. We next focused on proteins exclusively regulated in severe obstructive nephropathy and identified Arginase 1 as a potential candidate molecule involved in the development of obstructive nephropathy, located at the crossroad of pro- and antifibrotic pathways. The reduced urinary abundance of Arginase 1 in obstructive nephropathy was verified in independent clinical samples using both Western blot and MRM analysis. These data were confirmed in situ in kidneys obtained from a mouse obstructive nephropathy model. In addition, we also observed increased expression of Arginase 2 and increased total arginase activity in obstructed mouse kidneys. mRNA expression analysis of the related arginase pathways indicated that the pro-fibrotic arginase-related pathway is activated during obstructive nephropathy. Taken together we have identified a new actor in the development of obstructive nephropathy in newborns using quantitative urinary proteomics and shown its involvement in an in vivo model of disease. The present study demonstrates the relevance of such a quantitative urinary proteomics approach with clinical samples for a better understanding of the pathophysiology and for the discovery of potential therapeutic targets.

Arginine and asymmetric dimethylarginine in pregnant women with major depression.

OBJECTIVE: Depression has been associated with vascular dysfunction, which may be of particular relevance in pregnancy. Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-arginine play a critical role in vascular function. The objective of this study was to investigate differences in ADMA, SDMA, and L-arginine among pregnant women with major depression compared with pregnant women without depression. METHODS: A case-control study was conducted in 21 depressed pregnant women and 42 matched controls. Maternal plasma ADMA, SDMA, and L-arginine were quantified, as well as C-reactive protein and urine excretion of ADMA, SDMA, L-arginine, and Arginase I. RESULTS: Plasma L-arginine and ADMA levels were significantly lower in the first trimester in women with depression (mean [standard deviation = 37.0 [9.2] and 0.298 [0.06] µM, respectively) compared with matched controls (42.1 [11.4] and 0.336 [0.08] µM, p = .004 and p = .002, respectively) and across pregnancies (p < .001 both). Depressed pregnant women had higher levels of plasma C-reactive protein (7.5 [3.7] versus 5.1 [4.0] µg/ml, p = .027), but no differences in urine excretion of ADMA, SDMA, or L-arginine, or plasma levels of Arginase I (p > .10). CONCLUSIONS: Pregnant women with depression show lower plasma levels of L-arginine and ADMA. These differences are not explained by urinary excretion or Arginase I levels. The mechanism responsible for the observed differences in depressed pregnant women requires further research.

The assessment of nephrotoxic effect of organophosphorous pesticides based on the determination of the activity of some selected enzymes in urine.

Pesticides and their metabolites are excreted mainly by the kidneys. The effect of these compounds on the kidney parenchyma was evaluated on the basis of determinations of the activity of the following enzymes: alkaline phosphate, N-acetylglucosaminidase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase and arginase in urine of workers employed at the department producing organophosphorous pesticides (32 males and 53 females) as well as those employed at the production of chlorfenvinphos (35 males). The activity of most of the estimated enzymes was significantly higher as compared to control groups. The dynamic of changes of enzyme activity was traced in the workers employed at the department producing chlorfenvinphos over their first 18 months of employment.