Urine vapor pattern for olivopontocerebellar degeneration.

Autosomal dominant olivopontocerebellar degeneration was evaluated in a family numbering 414 living members. Urine samples were obtained from 5 affected and 5 unaffected not at-risk family members after 4 days on a synthetic diet. 159 urine vapor constituents were measured by gas-liquid and ion-exchange chromatography and a non-correlation index was calculated. 2 distinct populations of urine vapor patterns were identified which conformed to the normal and disease affected groups, thus a diagnostically useful pattern for this disease in this family has been demonstrated which will be helpful in genetic counselling and potential elimination of the disease.

[Urinary electrolyte excretion in autosomal dominant polycystic kidney]. / Urinna ekskretsiia na elektroliti pri avtozomna dominantna bubrechna polikistoza.

In 33 patients with autosomal dominant renal polycystosis the urine excretion of the electrolytes sodium and potassium was examined and analyzed in relation to the renal function and the arterial pressure. The clearances, the urine ratio and the excreted fractions of both electrolytes were calculated. It was established that by normal renal function and without arterial hypertension there were no significant differences in the parameters studied between the patients and the healthy controls. In the patients with arterial hypertension and preserved renal function the sodium clearance and urine excretion were lower, but the differences with the normotensive patients were not statistically significant. In the patients with chronic renal failure (when diuretic was applied) higher mean values of the excreted fractions of sodium and potassium were established. The results support the thesis that hypertension in renal polycystosis is of volumetric character.

Urinary hyperglycosylated hCG in first trimester screening for chromosomal abnormalities.

Hyperglycosylated human chorionic gonadotrophin (H-hCG), also known as Invasive Trophoblast Antigen or ITA, is a unique metabolic variant of hCG with more complex oligosaccharide side chains. Concentrations are independent of regular hCG. Urine H-hCG has recently proved to be a highly sensitive marker for Down syndrome screening in the second trimester of pregnancy. We evaluated H-hCG as a potential marker in the first trimester of pregnancy. Maternal urine samples were collected from 10(+0) to 11(+6) weeks of gestation prior to genetic analysis and stored in frozen form. Samples from eight cases of Down syndrome, two cases of trisomy 13, one case of trisomy 18, and 55 control pregnancies were hand-carried frozen to the USA and tested blindly. Samples were tested in a specific H-hCG immunoassay and values were normalized to creatinine concentration. Values were plotted against gestational age, and multiples of control pregnancy median (MoM) calculated. The median level of the MoMs of the eight Down syndrome cases was 3.6 MoM. Five of the eight Down syndrome cases exceeded the 90th centile of the 55 unaffected cases. The MoMs of the trisomy 13 and 18 pregnancies were 0.2, 0.2 and 0.3. All three cases were under the 10th centile of unaffected pregnancies. The results of this study indicate that H-hCG testing may be useful in screening for Down syndrome in the first trimester of pregnancy. Further studies are needed to assess the potential screening values of urine H-hCG and the combination of this test with free beta-subunit, PAPP-A and other markers for Down syndrome in the first trimester of pregnancy.

A vertical (pseudodominant) pattern of inheritance in the autosomal recessive disease primary hyperoxaluria type 1: lack of relationship between genotype, enzymic phenotype, and disease severity.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of alanine:glyoxylate aminotransferase (encoded by the AGXT gene). Primary hyperoxaluria type 1 is characterized by the elevated urinary excretion of oxalate and glycolate, and the deposition of insoluble calcium oxalate in the renal parenchyma and urinary tract. In the present study, we investigated an unusual family containing four affected individuals in two different generations. Based on our genetic, enzymic, metabolic, and clinical analyses, we have come to the following conclusions. First, although the pattern of inheritance of PH1 is usually horizontal (ie, all patients in the same generation), as expected for an autosomal recessive disease, it can sometimes show a vertical (pseudodominant) pattern of inheritance (ie, patients in more than one generation) due to the segregation within a family of three, rather than two, mutant AGXT alleles. Second, affected members of such a family can manifest very different clinical phenotypes both within and between generations. Although the clinical differences between generations might be at least partly due to differences in AGXT genotype, differences can equally occur within the same generation in individuals who possess the same AGXT genotype. Finally, individuals with PH1 at the level of the AGXT genotype might remain asymptomatic and undiagnosed for many years. The consequences of these findings for the clinical management and genetic counseling of families with PH1 are profound and wide-ranging.