[Chemotherapy-induced fetal anemia in maternal acute myelocytic leukemia]. / Chemotherapieinduzierte fetale Anämie bei akuter myeloischer Leukämie der Mutter.

This article discusses the management of a pregnancy of a 32-year-old primigravida with acute myelocytic leukemia treated with induction chemotherapy starting in the 20 + 5 week of gestation. Sonographic monitoring showed evidence of fetal ascites and anemia that could be treated with an intrauterine fetal transfusion. After maternal recovery, a caesarean section was performed in the 27 + 5 week of gestation. We delivered a vivid eutrophic female prematurely. The infant showed persisting signs of myelosuppression. Two further transfusions had to be performed. The present report describes the interdisciplinary therapeutic management when polychemotherapy during pregnancy is necessary for the mother. Cases of acute leukemia in pregnancy are complicated by severe prenatal risks caused by the hematologic illness and by the immediate beginning of chemotherapy. In the third trimester premature delivery is preferable to intrauterine exposition to cytostatic agents. In the second trimester the pregnancy has to be monitored for the typical risks and complications of chemotherapy. Fetal cytotoxic myelosuppression is detectable by prenatal observation so that interventional strategies are feasible.

The Uromodulin C744G mutation causes MCKD2 and FJHN in children and adults and may be due to a possible founder effect.

Autosomal dominant medullary cystic kidney disease type 2 (MCKD2) is a tubulo-in terstitial nephropathy that causes renal salt wasting, hyperuricemia, gout, and end-stage renal failure in the fifth decade of life. This disorder was described to have an age of onset between the age of 20-30 years or even later. Mutations in the Uromodulin (UMOD) gene were published in patients with familial juvenile hyperuricemic nephropathy (FJHN) and MCKD2. Clinical data and blood samples of 16 affected individuals from 11 different kindreds were collected. Mutational analysis of the UMOD gene was performed by exon polymerase chain reaction (PCR) and direct sequencing. We found the heterozygous C744G (Cys248Trp) mutation, which was originally published by our group, in an additional four kindreds from Europe and Turkey. Age of onset ranged from 3 years to 39 years. The phenotype showed a variety of symptoms such as urinary concentration defect, vesicoureteral reflux, urinary tract infections, hyperuricemia, hypertension, proteinuria, and renal hypoplasia. Haplotype analysis showed cosegragation with the phenotype in all eight affected individuals indicating that the C744G mutation may be due to a founder effect. Moreover, we describe a novel T229G (Cys77Gly) mutation in two affecteds of one kindred. Three of the affected individuals were younger than 10 years at the onset of MCKD2/FJHN. Symptoms include recurrent urinary tract infections compatible with the published phenotype of the Umod knockout mouse model. This emphasizes that MCKD2 is not just a disease of the young adult but is also relevant for children.

A stepwise approach to the treatment of early onset nephrotic syndrome.

We have retrospectively reviewed our single-center experience of the treatment of early onset nephrotic syndrome (NS). From 1991 to 1998, ten children with NS were treated. Kidney biopsy showed focal sclerosis (n=1), diffuse mesangial sclerosis (n=7), and congenital NS of the Finnish type (n=2). Associated conditions included incomplete Drash syndrome (n=1), Galloway-Mowat syndrome (n=1), and severe mental and motor retardation of unknown origin (n=3). From 1991 to 1997, five children with NS were treated. Bilateral nephrectomy (NX) was performed in three, one patient with severe retardation died at 4 years and NX was not performed in one patient who showed satisfactory growth and development. Three of these children were dialyzed and two were successfully transplanted. One patient was transplanted without previous dialysis. From 1997 to 1998, five children were treated with a regimen that included captopril and indomethacin (CAPTO/INDO). CAPTO/ INDO was successful in increasing serum protein in all patients and producing growth and development in four patients. In two patients CAPTO/INDO was successful only after unilateral NX. Our experience indicates that CAPTO/INDO may be a valuable treatment in patients with early onset NS. An individualized stepwise approach including unilateral NX should be considered to achieve optimal results.