Preliminary Screening Results of Fabry Disease in Kidney Transplantation Patients: A Single-Center Study.

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficiency of alfa-galactosidase A (AGALA) and leads to progressive impairment of renal function in almost all male patients and in a significant proportion of female patients. FD is underdiagnosed or even misdiagnosed in patients undergoing kidney transplantation. We initiated a selective screening study for FD among kidney transplant patients in our center. In this study, 1095 male and female patients were included. Dried blood samples on Guthrie papers were used to analyze galactosidase A enzyme for male patients. Genetic analyses were performed in all female and male patients with low enzyme activity. In total, 648 female and 447 male patients with functioning grafts were evaluated. Among 1095 patients, 5 male patients had AGALA activity below threshold and 3 female patients had galactosidase alpha gene DNA variations. One male patient had a disease-causing mutation. The other 4 patients had polymorphisms causing low enzyme activity. All the 3 female patients had mutations that were associated with FD according to Human Gene Mutation Database (ID: CM025441). In contrast, these mutations were reported as unknown clinical significance in Clinvar (rs149391489). The patients with clinical findings suggesting FD were planned to be analyzed for Lyso Gb3. In our selective screening study, 8 variations were found among 1095 kidney transplantation patients, which needs further investigation to determine causes of FD. Clinical findings, physical examination, and family history are also necessary to evaluate the genetic changes as a mutation in this selected population.

A prospectively validated nomogram for predicting the risk of chemotherapy-induced febrile neutropenia: a multicenter study.

PURPOSE: There is clinical need to predict risk of febrile neutropenia before a specific cycle of chemotherapy in cancer patients. METHODS: Data on 3882 chemotherapy cycles in 1089 consecutive patients with lung, breast, and colon cancer from four teaching hospitals were used to construct a predictive model for febrile neutropenia. A final nomogram derived from the multivariate predictive model was prospectively confirmed in a second cohort of 960 consecutive cases and 1444 cycles. RESULTS: The following factors were used to construct the nomogram: previous history of febrile neutropenia, pre-cycle lymphocyte count, type of cancer, cycle of current chemotherapy, and patient age. The predictive model had a concordance index of 0.95 (95 % confidence interval (CI) = 0.91-0.99) in the derivation cohort and 0.85 (95 % CI = 0.80-0.91) in the external validation cohort. A threshold of 15 % for the risk of febrile neutropenia in the derivation cohort was associated with a sensitivity of 0.76 and specificity of 0.98. These figures were 1.00 and 0.49 in the validation cohort if a risk threshold of 50 % was chosen. CONCLUSIONS: This nomogram is helpful in the prediction of febrile neutropenia after chemotherapy in patients with lung, breast, and colon cancer. Usage of this nomogram may help decrease the morbidity and mortality associated with febrile neutropenia and deserves further validation.

Analysis of the sphingomyelin phosphodiesterase 1 gene (SMPD1) in Turkish Niemann-Pick disease patients: mutation profile and description of a novel mutation.

Niemann-Pick disease (NPD) is a lysosomal storage disorder that results from the deficiency of a lysosomal enzyme, acid sphingomyelinase. Niemann-Pick disease type A and B is caused by mutations in the sphingomyelin phosphodiesterase gene (SMPD1) coding for ASM. The aim of this study was to evaluate the spectrum of SMPD1 gene mutations in Turkish NPD patients and to study genotype-phenotype associations. We present a molecular analysis of 10 Turkish NPD type A/B patients. Four of the patients had type A and six had type B NPD. All mutant SMPD1 alleles were identified, including 5 different mutations, 1 of which was novel. These mutations included three missense mutations: c.409T>C (p.L137P), c.1262 A>G (p.H421R) and c.1552T>C (p.L549P), a common frameshift mutation in codon 189, identified in three patients, is caused by the deletion of the 567T, introducing a stop codon 65 amino acids downstream (p.P189fsX65), and a novel frameshift mutation c.1755delC (p.P585PfsX24) which was not reported previously.

A monocentric pilot study of an antioxidative defense and hsCRP in pediatric patients with glycogen storage disease type IA and III.

BACKGROUND AND AIMS: Patients with glycogen storage disease type Ia (GSD Ia) and III (GSD III) do not develop premature atherosclerosis despite hyperlipidemia. The aim of the study was to investigate the oxidative-antioxidative conditions and high sensitivity C-reactive protein (hsCRP) levels in patients with glycogen storage disease type Ia and III. METHODS: We measured lipid profile and lipid peroxidation products in comparison with hsCRP and antioxidative status: trolox equivalent antioxidant capacity, total antioxidant activity, proteinaceous antioxidant enzymes (catalase, superoxide dismutase, paraoxonase, arylesterase), aqueous antioxidants (vitamin C, uric acid, bilirubin, total protein) and lipid-soluble antioxidants (alpha-tocopherol, beta-carotene). The study included 50 individuals: 22 with GSD Ia, 9 with GSD III, and 19 healthy subjects. RESULTS: GSD Ia patients showed a marked hypertriglyceridemia, whereas GSD III patients demonstrated hypercholesterolemia with elevated LDL-cholesterol and decreased HDL-cholesterol levels. Lipid peroxidation levels increased in both GSD groups. The antioxidant activity elevated in GSD Ia group. No significant differences were found in the activities of antioxidant enzymes. Uric acid and alpha-tocopherol levels increased, however, vitamin C and beta-carotene reduced in both GSD groups. The hsCRP levels did not differ among the groups. CONCLUSIONS: In summary our study revealed normal levels of hsCRP in spite of the dyslipidemic status in both GSD patients. The increased plasma antioxidative defense in GSD Ia might be attributed not only to the elevated uric acid but also to the supplemented vitamin E levels. These findings should motivate further investigations in the area of atherosclerotic escape of GSDs.

Renal involvement as a rare complication of Dorfman-Chanarin syndrome: a case report.

Dorfman-Chanarin syndrome is a rare, autosomal recessive inherited lipid storage disease with congenital ichthyotic erythroderma due to an acylglycerol recycling defect. It is characterized by accumulation of neutral lipids in different tissues. Liver, muscle, ear, eye, and central nervous system are generally involved, so we presented a patient with severe ichthyosis, lipid vacuoles in neutrophils, and multiorgan involvement including a very rare complication, renal involvement. A 7-month-old girl was presented with frequent respiratory infection, congenital ichthyotic erithroderma and suspicion for immune deficiency. On her physical examination hepatomegaly, developmental delay, palmar and plantar hyperkeratosis and increased deep tendon reflexes with clonus and high tonus were found. Laboratory investigations revealed elevation at transaminases levels, hypoalbuminemia, hypergammaglobulinemia, presence of autoantibodies and eosinophilia. Vacuolization in leukocytes confirmed Dorfman-Chanarin syndrome, whereas no mutation at RAG1-2 and ARTEMIS genes ruled-out immune deficient status of the patient. At the age of eight months the patient died from severe renal failure. Her necropsies demonstrated microvesicular lipid accumulation not only at the liver but also at the renal species. The variability of involvement of different systems in Dorfman-Chanarin syndrome is well described, however the renal findings has not been reported previously at the literature.

Percutaneous rhizotomy of the articular nerve of Luschka for low back and sciatic pain.

The results of percutaneous facet rhizotomy for the treatment of low back and sciatic pain in 30 patients are reported. Satisfactory results were obtained in 76% of cases. No complications were found. This procedure should be tried in every patient with low back and extremity pain and no major neurological deficit before resorting to laminectomy.

Increased intracranial pressure associated with spinal cord tumours.

Two cases of spinal cord tumour associated with increased intracranial pressure are reported and the 44 cases described in the literature are reviewed. The different hypotheses produced to explain the pathogenic mechanism of this syndrome are discussed. We think that several factors working together, rather than an isolated mechanism, take part in the production of this syndrome.

Changes in serum and cerebrospinal fluid enzyme activity after head injury.

We studied simultaneously in serum (S) and CSF (L) the enzyme activities of GOT, GPT, LDH, ICDH, MDH, ALD, and CPK in 28 patients with head injuries divided into three groups according to the severity of the trauma. We found a correlation between severity of brain lesion and enzyme activity. The best correlation was found for SGOT, SCPK, LGOT, LLDH, LMDH and LCPK. We do not believe that enzyme activity is of prognostic value. We think that further studies should be made of the specific isoenzymes of the Central Nervous System.

The occult intrasacral meningocele.

Three cases of occult intrasacral meningocele, one of them with an intrasacral and presacral neurofibroma, are reported. The literature is briefly reviewed. Pathogenesis, clinical picture, radiological findings and surgical treatment are discussed.