A case of type I Gaucher disease with cardiopulmonary amyloidosis and chitotriosidase deficiency.

Severe cardiopulmonary amyloidosis developed several months after a total splenectomy in a patient with type 1 Gaucher disease and led within a year to his death at 48 years of age. The autopsy findings were dominated by extensive pulmonary and cardiac amyloid infiltration. No Gaucher cells were found in the lungs. Aside from a glucocerebrosidase deficiency the patient was also deficient in chitotriosidase, an enzyme whose activity is usually greatly increased in the serum of Gaucher patients. Analysis of mutations in the glucocerebrosidase gene revealed heterozygosity for N370S and D409H mutations. The normal amount of glucocerebrosidase was found in the spleen by Western blotting. We suggest that amyloidosis should be considered in the differential diagnosis of severe cardiopulmonary disease in Gaucher patients.

[Congenital aplastic anemia caused by parvovirus B19 infection]. / Kongenitální aplastická anémie zpusobená infekcí parvovirem B19.

Human parvovirus B19 causes the fifth disease (erythema infectiosum) in childhood. Intrauterine infection by parvovirus in immunocompromised fetus can lead to the severe congenital aplastic anemia. Here we report the case of 2.5-year-old girl with congenital infection with parvovirus B19. The girl was born as a pre-term baby with hydrops, congenital aplastic anemia, and low level of immunoglobulins IgG and IgM. She depended on the repeated blood transfusions and she did not respond to erythropoietin therapy. The parvovirus B19 infection in bone marrow was detected by polymerase chain reaction and its therapy started with intravenous administration of immunoglobulins. Hemoglobin reached normal level one year later, but low levels of parvovirus B19 were detectable for another 6 months. Immunoglobulin treatment was finished when the virus could not be detected in the circulation. However, one-month later parvovirus B19 DNA was detected again. The two months course of immunoglobulin treatment was repeated, and the DNA analysis of blood cells for parvovirus B19 has been negative since then. Five months after the final withdrawal of the immunoglobulin therapy the girl is in a good shape and all lab tests, except for the decreased levels of IgM, are within the normal range. The PCR monitoring of the presence of parvovirus B19 DNA in blood and bone marrow cells during and after the treatment of congenital aplastic anemia caused by parvovirus B19 chronic infection becomes the necessity for the rational therapy.

[Enzyme therapy in children with severe forms of Gaucher's disease]. / Enzymová terapie u detí s tezkou formou Gaucherovy nemoci.

The enzyme therapy with Ceredase in patients with Gaucher's disease is at present probably the most expensive treatment in the whole world. One-year treatment of an adult patient with Gaucher's disease costs more than 7 million crowns. Indications for treatment in individual patients as well as financial provisions are so far problematic in the Czech Republic. From a total of 28 patients of varying age with Gaucher's disease diagnosed by the authors Ceredase was administered to two boys with a severe course of the disease. Within one year of treatment the health status of both children improved, growth became normal, the spleen diminished in size by 20-35%, haematological manifestations of hypersplenism are receding, there was a 32-46% decline of the activity of serum chitotriosidase and biochemical parameters of the disease improved.

Analysis of the beta-glucocerebrosidase gene in Czech and Slovak Gaucher patients: mutation profile and description of six novel mutant alleles.

The aim of this study was to characterize the spectrum of 13-glucocerebrosidase gene mutations in Czech and Slovak Gaucher patients and to study genotype/phenotype associations. We have analyzed fifty-eight chromosomes from twenty-six type I, two type 2, and one type 3 13-glucocerebrosidase deficient subjects by direct sequencing of PCR products. Fifty-eight mutant alleles were identified. Seventy-eight percent of mutant alleles carried common mutations (N370S 28/58, L444P 11/58, recNciI 5/58, and IVS2(+1)A 1/58), the remaining twenty-two percent carried rare and private mutations (1263del55, l326insT, S196P, rec(g4889-6506), 2O3delC, G202E, F216Y, R257X, R12OW, R359Q, S1O7L, L444P + V460V, and D409H + T369M). Six of these alleles have not been previously described (rec(g4889-6506), 1326insT, SI96P. G202E, D409H + T369M, and L444P + V460V). The most common genotypes were N370S/L444P (8/29). N370S/recNciI (5/29), and N370S/N370S (2/29). The spectrum of the mutations is characteristic for a Caucasian (non-Jewish) population, with N370S, L444P and recNciI being the most prevalent mutations. The absence of the mutation 84insG that is frequently associated with severe bone disease may have contributed to the low incidence of severe bone disease in Czech and Slovak Gaucher subjects.

Hb Nottingham or alpha 2 beta 2 98 (FG5) Val-->Gly in a Czech child.

We report a fourth case of Hb Nottingham [alpha 2 beta 2 98 (FG5) Val-->Gly] observed in an 8-year-old girl in the Czech Republic with clinical and laboratory symptoms of severe hemolytic anemia. The unstable hemoglobin probably represents a de novo mutation, since the parents of the patient and the two siblings do not exhibit any hematological abnormalities. Splenectomy had a beneficial effect on the degree of hemolysis, as well as on the Hb level.