Delayed hemolysis, elevated liver enzymes, low platelet count syndrome in succession of switches of preventive anticoagulant treatment in a 41-year-old patient with a history of recurrent assisted implantation failures: a case report.

BACKGROUND: For the past decades the mean age of primiparae in Western societies is constantly increasing. At the same time, there is a growing demand for assisted reproductive technologies such as in vitro fertilization and intracytoplasmic sperm injection. Subsequently, a higher prevalence of pregnancy-associated diseases such as gestational hypertension and preeclampsia is observed. To improve pregnancy rates after in vitro fertilization/intracytoplasmic sperm injection and to reduce the risk of pregnancy-associated diseases with a cardiovascular pathophysiology, two anticoagulants are the focus of current research: low molecular weight heparin and acetylsalicylic acid (aspirin). CASE PRESENTATION: A 41-year-old white woman, gravida 3, para 0, received low molecular weight heparin to reduce the risk of abortion after five unsuccessful intracytoplasmic sperm injections and two miscarriages. She autonomously discontinued the medication with low molecular weight heparin at 12 weeks and 2 days of gestation and took aspirin instead until 24 weeks and 2 days of gestation as preeclampsia prophylaxis. However, the pregnancy ended with an urgent cesarean section at 27 weeks and 4 days of gestation due to a fast progressing hemolysis, elevated liver enzyme levels, and low blood platelet count syndrome, a potentially life-threatening variant of preeclampsia. CONCLUSION: Based on the current demographic trend toward late-in-life pregnancy it is mandatory to establish clear guidelines concerning preventive treatment options of preeclampsia for patients with risk factors. The establishment of a special first-trimester screening for these women should be discussed. Moreover, it is necessary to raise the awareness among physicians of these contemporary issues to guarantee the best possible medical care.

Prenatal findings in four consecutive pregnancies with fetal Pierson syndrome, a newly defined congenital nephrosis syndrome.

OBJECTIVE: To describe the prenatal findings in Pierson syndrome, a newly defined autosomal recessive entity, comprising congenital nephrotic syndrome (CNS) with diffuse mesangial sclerosis and distinct eye abnormalities due to LAMB2 mutations. METHODS: Serial prenatal ultrasound examinations were performed in four consecutive pregnancies affected by Pierson syndrome in the same family. LAMB2 mutations were demonstrated in retrospect by direct sequencing of the gene in the newborn index patient and three abortuses. RESULTS: Fetal ultrasound consistently revealed marked renal hyperechogenicity associated with variable degree of pyelectasis. These features were detectable by 15 weeks of gestation in all fetuses. Hydrops fetalis due to severe hypalbuminemia demonstrated by chordocentesis occurred in one fetus. Placentas were significantly enlarged. Development of oligohydramnios indicated prenatal decline of renal excretory function. Anencephaly was detected in another fetus with molecularly proven Pierson syndrome at 12 weeks of gestation. CONCLUSION: We conclude that Pierson syndrome has to be considered in the differential diagnosis of nephrotic disorders with prenatal onset. Ultrasound criteria for differentiation from the most common type of CNS-congenital nephrosis of the Finnish type (CNF)-are discussed. Because of its prognostic relevance, we advocate molecular genetic testing of LAMB2 in any case of prenatally detected nephrotic syndrome with negative results of NPHS1 mutational screening, especially in the presence of the typical sonomorphologic findings of the kidneys and the development of oligohydramnios.

Human laminin beta2 deficiency causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities.

Congenital nephrotic syndrome (CNS) is clinically and genetically heterogeneous, with mutations in WT1, NPHS1 and NPHS2 accounting for part of cases. We recently delineated a new autosomal recessive entity comprising CNS with diffuse mesangial sclerosis and distinct ocular anomalies with microcoria as the leading clinical feature (Pierson syndrome). On the basis of homozygosity mapping to markers on chromosome 3p14-p22, we identified homozygous or compound heterozygous mutations of LAMB2 in patients from five unrelated families. Most disease-associated alleles were truncating mutations. Using immunohistochemistry and western blotting we could demonstrate that the respective LAMB2 mutations lead to loss of laminin beta2 expression in kidney and other tissues studied. Laminin beta2 is known to be abundantly expressed in the glomerular basement membrane (GBM) where it is thought to play a key role in anchoring as well as differentiation of podocyte foot processes. Lamb2 knockout mice were reported to exhibit congenital nephrosis in association with anomalies of retina and neuromuscular junctions. By studying ocular laminin beta2 expression in unaffected controls, we detected the strongest expression in the intraocular muscles corresponding well to the characteristic hypoplasia of ciliary and pupillary muscles observed in patients. Moreover, we present first clinical evidence of severe impairment of vision and neurodevelopment due to LAMB2 defects. Our current data suggest that human laminin beta2 deficiency is consistently and specifically associated with this particular oculorenal syndrome. In addition, components of the molecular interface between GBM and podocyte foot processes come in the focus as potential candidates for isolated and syndromic CNS.

Congenital nephrosis, mesangial sclerosis, and distinct eye abnormalities with microcoria: an autosomal recessive syndrome.

We observed the occurrence of congenital nephrotic syndrome (CNS) and distinct ocular anomalies in two unrelated families. Eleven children from both families presented with a similar course of renal disease starting with nephrotic syndrome and renal failure prenatally or immediately after birth that resulted in death before the age of 2 months. Kidney histopathology showed diffuse mesangial sclerosis (DMS). Clinically obvious eye abnormalities were recognized in six of the eight patients in whom sufficient clinical data were available. Ocular anomalies included enlarged or large appearing corneae in some cases suggesting buphthalmos, and extremely narrow, nonreactive pupils (microcoria). Pathological examination of the eyes of two aborted fetuses revealed a more complex ocular maldevelopment including posterior lenticonus as well as anomalies of cornea and retina. On the basis of these observations and other cases in the literature, we delineate a previously unrecognized distinct entity characterized by congenital nephrotic syndrome, DMS, and eye abnormalities with microcoria as the leading clinical feature. Pedigrees of affected families with parental consanguinity support autosomal recessive inheritance. We propose that this syndrome should be designated microcoria-congenital nephrosis syndrome or Pierson syndrome. Possible overlap with Galloway-Mowat syndrome and relations to other oculo-renal syndromes are discussed.