Hyperhomocysteinemia: a trigger for complement-mediated TMA?

A 34-year-old man of North African descent was referred to the emergency department because of malignant hypertension (220/113 mmHg), acute visual disturbances and acute kidney failure (serum creatinine 14.0 mg/dL). Blood analysis was compatible with thrombotic microangiopathy (TMA). Kidney biopsy confirmed this diagnosis with histological changes including intimal edema, arteriolar thrombi, and severe tubulointerstitial damage. Fundoscopy showed hypertensive retinopathy stage IV. Subsequent biochemical screening revealed normal complement testing and a marked elevation in homocysteine concentration (161 µmol/L; normal value 7-15 µmol/L). Other secondary causes of TMA were excluded. Further genetic testing for cobalamin C (cblC) deficiency showed no pathogenic mutations in the MMACHC gene. However, a homozygous c.665C>T polymorphism (NM_005957.4) in the methylenetetrahydrofolate reductase (MTHFR) gene was found explaining the severe hyperhomocysteinemia due to reduced activity of MTHFR. Additional genetic testing for alternative complement pathway proteins showed mutations in the genes encoding factor H and factor B, both categorized as possibly pathogenic using mutation prediction software. This is the first described case of TMA in a patient with severe hyperhomocysteinemia caused by a genetic defect other than cblC. We postulate that endothelial damage due to hyperhomocysteinemia and hypertension could have triggered the TMA episode in this patient with two possible predisposing pathogenic mutations in the alternative complement pathway. Furthermore, our case demonstrates the need for complete full diagnostic testing in patients with TMA.

Cinacalcet for managing secondary hyperparathyroidism in dialysis patients in clinical practice in Belgium: a 16-month observational study (ECHO-B).

In Belgium, the calcimimetic cinacalcet is initially reimbursed for < or = 4 months in dialysis patients with secondary hyperparathyroidism (SHPT) and intact parathyroid hormone (iPTH) > or = 800 pg/mL, or iPTH 300-800 pg/ mL and Ca x P > 55 mg 2/dL2 despite > or = 6 months' optimal treatment with vitamin D sterols and/or phosphate binders. The Belgian, multicentre, observational study ECHO-B evaluated cinacalcet in such patients. Patients who began cinacalcet treatment after March 1, 2007 were eligible. Data were collected retro/prospectively from 6 months before until 16 months after starting cinacalcet (whether or not cinacalcet was continued). Median iPTH was markedly elevated (816 [IQR 551-991] pg/mL) at baseline (the time of starting cinacalcet), but decreased continuously over the course of the study, reaching a value of 414 pg/mL (IQR 240-641; median change -41%) at 4 months, 335 pg/mL (IQR 159-616; -60%) at 12 months and 250 pg/mL (IQR 172-436; -64%) at 16 months. Reductions in serum calcium (-7%) and phosphorus (-13%) were already (near) maximal at 4 months. The primary outcome (iPTH 150-300 pg/mL and/or a > or = 30% reduction within 4 months of starting cinacalcet; criterion for continued reimbursement in Belgium) was achieved in 65/81 patients (80%; 95% CI 72-89%). Results show that in dialysis patients with SHPT in real-life clinical practice, mineral metabolism improves after starting cinacalcet: our study findings suggest that PTH levels may continue decreasing after 12 months' treatment in this setting.

Autoimmune pancreatitis and extrapancreatic manifestations of IgG4-related sclerosing disease.

In a review of the literature concerning autoimmune pancreatitis we had special interest for the concept of IgG4-related pathology as a systemic disease with several clinical manifestations. In general, IgG4-positivity can not only be found in the pancreas, but also at the level of the kidneys, extrahepatic biliary ducts, gallbladder, lungs, salivary glands, lacrimal glands, retroperitoneal tissue, ureters, prostate, meninges and lymph nodes. IgG4 seems to be a central key player in the pathophysiology of this disease.

A follow-up study on 12 prenatally diagnosed boys with Klinefelter syndrome.

Longitudinal follow-up data on males with Klinefelter syndrome are still scarce. In the present study we collected data on the general and psychosocial development of 12 prenatally diagnosed boys with Klinefelter syndrome.

Immunoglobulin related amyloidosis presenting as isolated lymph node and pulmonary involvement.

Here we present an unusual case of a 53-year old patient presenting AL-kappa amyloidosis with diffuse-type amyloidosis of lungs, lymph nodes and pleura. The underlying pathology was a B-cell immunoglobulin-secreting non-Hodgkin lymphoma, as proven by the presence of a monoclonal B-cell population in the bone marrow. Diffuse parenchymal infiltration of the lungs is extremely rare in non-systemic amyloidosis, with only 4 previous cases having been reported in the English literature.

Pseudomonas pickettii as a cause of pseudobacteremia.

An outbreak of pseudobacteremia caused by Pseudomonas pickettii biovariant 1 is reported. The common source was the aqueous chlorhexidine solution prepared by the hospital pharmacy. The contamination problem caused by the antiseptic solution was eventually solved by a series of preventive measures.