[Oculo-cerebro-renal Lowe syndrome: clinical, biochemical and molecular studies in a Moroccan patient]. / Syndrome oculo-cérébro-rénal de Lowe: étude clinique, biochimique et moléculaire chez un patient marocain.

The oculo-cerebro-renal syndrome of Lowe is a rare X-linked disorder, caused by the inositol biphosphate 5-phosphatase deficiency, localized to the Golgi complex. Several mutations were reported in patient's OCRL gene leading to enzyme deficiency. We report a Moroccan case of OCRL syndrome of Lowe with a neo mutation in exon 10. The patient aged of 19 months was referred to our medical centre because of a psychomotor retardation. He had a medical history of eye abnormalities including cataract and bilateral glaucoma, diagnosed when he was 5 weeks old. Cataract has been treated after chirurgical therapy but ocular hypertonia persisted. Physical examination revealed an axial hypotonia and walking difficulties. Laboratory tests revealed a moderate acidosis (20 mmol/L), a slight decrease of serum phosphate level (24 mg/L) and an increased serum phosphatase activity. Further studies showed mild proteinuria, urinary bicarbonates loosing and generalised hyperaminoaciduria. Based on both clinical and biological data, Lowe syndrome has been suggested. In this context, molecular investigation has been performed using dHPLC/sequencing techniques which allow identifying an original mutation c.776T>C (p.Phe259Ser), localized on the exon 10 of the OCRL gene. The mutation was not found in the probant's mother suggesting a neo mutation. Lowe syndrome is a rare hereditary X-linked disorder resulting from a variety of heterogeneous mutations of OCRL gene. Indeed, numerous mutations have been reported, variations were noted concerning their localization as well as their type. To our knowledge, this is the first report of the neo mutation c.776T>C of OCRL gene and the first published case report of the Lowe syndrome in a Moroccan patient.

Tests to localize free proteolytic enzymes in vivo by 14C-cysteine-aprotinin.

Aprotinin, a polyvalent protease inhibitor from bovine organs, has been labelled with 14C-cysteine in 6 M urea to produce a radioactive conjugate, without effect on the inhibitor activity. 138x10(3) dpm of radioactive product, containing 5 mg of protein (20.000 kal. inhibitor units) in 5 ml of Locke's solution were perfused in anesthetized rabbits via ascending aorta. Then the anesthetized rabbit was killed and specimens of some organs were admitted to autoradiographic analysis. Small intestine, ischiatic nerve and testis have been the most rich radiolabelled organs (+++). In kidney, stomach, large intestine, liver and eye the radiolabelled aprotinin was found in fair amounts (++); while in pancreas, spleen, spinal cord, brain, cava vein and aorta of rabbit the 14C-cysteine-Aprotinin was practically undetectable by autoradiography.

Method for measurement of human urinary kininase activity.

A method was developed to measure kininase activity in human urine. The method consists of dialysis of human centrifuged urine sample against phosphate buffer and partial fractionation of A-50 Sephadex column. The enzymatic property of urinary kininase, which destroys bradykinin when incubated, is estimated from its effect on a definite amount of bradykinin, using rat uterus.

Altered urinary excretion of human kininase activity in acute myocardial infarction.

This study concerns the determination of levels of human urinary kininase excretion in acute myocardial infarction (AMI). The results obtained by a biological method show that there is a significant reduction of the enzymatic activity in patients affected by AMI in comparison with normals (6.4 +/- 0.4 ng of destroyed bradykinin/min. versus 164.4 +/- 31.4 ng; P less than 0.001), while urinary kallikrein excretion was close to normal values.

Chemical relations between renal and urinary kallikrein of rat.

The ratio in micron-Moles between each aminoacid residue of both hydrolized renal and urinary kallikrein of rat, is about 1.00 +/- 0.3. Except for Glu, His and Glucosamine a good proportion between all residues of both enzymes was obtained. It is probable that the different molecular weight, respectively 40,000 for the renal kallikrein and 32,000 for the urinary enzyme, is an artefact of the different procedures used for the purification of rat kallikrein.

Purification of horse renal kallikrein and chemical relations with horse urinary kallikrein.

Kallikrein was purified from horse kidney by several steps of chromatographic procedure and by affinity chromatography on Sepharose-Concanavaline. Horse urinary kallikrein was previously purified by DE-32 hydroxylapatite and by Sephadex G-100 gel filtration. On the purified final sample of renal and urinary kallikrein the aminoacid composition and the gel electrophoretic molecular weight were determined. The ratio in micronMoles between each aminoacid residue of both hydrolyzed renal and urinary kallikrein of horse is about 1,00 +/- 0,30. Except for Pro, 1/2 Cys and basic aminoacid residues a good proportion was obtained. It is confirmed that the different molecular weight, respectively 47,500 for renal kallikrein and 28,000 for the urinary enzyme is an artefact of the different procedures used for the purification of horse kallikrein.

Altered urinary excretion of human kininase activity in hypertension.

This study describes the levels of urinary kininase activity in hypertension. Urinary kininase activity in essential and secondary hypertensive patients was higher than in controls (1010.2 +/- 102.7 versus 114.4 +/- 23.1 ng destroyed bradykinin/min.; p less than 0.001). In a group of hypertensive diabetics without nephropathy kininase activity in urine was decreased (46.0 +/- 12.7 ng destroyed bradykinin/min.). This investigation shows that in hypertension urinary kininase activity reaches higher levels. An inverse correlation was found between urinary kallikrein and urinary kininase activity from essential hypertensive patients.