Extended interval between enzyme therapy infusions for adult patients with Gaucher's disease type 1.

BACKGROUND: Enzyme replacement therapy (ERT) for Gaucher's disease with alglucerase or imiglucerase is efficacious, well-tolerated and safe. However, cost considerations, visits to medical facilities, potentially duration of theray for life, are issues of major concern to a proportion of treated patients and has, in some cases, led to the withdrawal of therapy. AIMS: To elucidate whether an extension of the interval between enzyme infusions to once every three weeks is as effective in maintaining the clinical responses achieved with the bi-monthly regimen. MATERIALS AND METHODS: Four patients with an optimal response to ERT (at 30 units/kg every two weeks for an average of 27 months), were subjected to enzyme dose/frequency changes that essentially constituted a reduction in cumulative dose over the treatment period. Patients were assessed every 6 months for alterations in haematological parameters, plasma chitotriosidase levels, liver and spleen size, and bone symptoms. RESULTS: All patients had to resume the previous infusion schedule of once every two weeks; one because of new bone marrow infiltrates, two because of visceral enlargement, and the fourth due to progressive anaemia. CONCLUSIONS: This limited experience suggests that a reduction in enzyme dose associated with an extended interval between infusions may lead to variable disease control, and underscores the need for individualization of enzyme therapy.

Carbamazepine induced transient monoclonal gammopathy and immunodeficiency.

Immune abnormalities have been found in many patients receiving anti-epileptic drugs. However, the effects of carbamazepine are still conflicting. We report the case of a 31-year-old woman who began carbamazepine treatment because of idiopathic epilepsy of adulthood. After three years of treatment she developed arthralgias and malaise. Complete immunologic evaluation showed a total absence of immunoglobulin M with decreased levels of immunoglobulin A, positive antinuclear antibodies and monoclonal paraproteinemia type IgG-kappa. The possibility of B cell lymphoma or myeloma was ruled out. Skin testing was negative. Bone marrow examination was normal. After carbamazepine discontinuation, levels of IgA and IgM increased until reaching normal values over 3 years. The monoclonal gammopathy of undetermined significance also disappeared over this period. During this period of immunodeficiency, the patient did not complain of any infectious complications.

[Leprosy: identification of an isolated case]. / Lepra: detección de un caso aislado.

Leprosy is an infrequent disease in Spain. 4,714 cases of leprosy was registered in the last national census (1979). The disease is still common in certain regions, such as Levant, Andalusia, Extremadura, Canary Island and Galicia. Lepromatous type is more frequent, a typical hallmark of endemies with low activity or characterized by regression. We report a patient affected of borderline lepromatous leprosy with the following characteristics: 1) the only known case in his locality, 2) lack of reaction after the treatment, and 3) due to its clinic, histological, and bacteriological characteristics was quite difficult to determine the leprosy's type. Even though the leprosy is an infrequent disease, it can be seen in everyday's practice, so that the internist and specialist. Have to know the disease in order to make an early diagnosis and to treat the patient effectively.

[Anemia secondary to lead poisoning. Our experience with 12 cases]. / Anemia secundaria a intoxicación por plomo. Nuestra experiencia a propósito de 12 casos.

BACKGROUND: A decrease in hemoglobin production is probably the main cause of anemia observed in patients poisoned by lead although hemolysis caused by the effects on membrane or by inhibition of other enzymes such as 5'-pyrimidine nucleotidase may also play a key role. The main lead exposure source comes from lead use in industry; however, outside occupational exposure, food and water consumption is the main cause of lead exposure. MATERIALS AND METHODS: Clinical and analytical characteristics are reported of twelve patients with lead poisoning of food and water source occurred in the last 14 years in two health areas in north Extremadura. RESULTS: The exposure source was wine, vinegar and olives in one case, hand-made brandy in five, water consumption in houses with lead piping, and in two cases the cause was not determined. The clinical picture was similar in all cases with the exception of one female patient who had encephalopathy and hepatic failure. Diagnosis was suggested by regenerative anemia with basophilic stippling of erythrocytes. All patients received oral calcium disodium EDTA. CONCLUSIONS: Lead poisoning in non-industrial areas is a rare entity. Nevertheless, owing to the use of artisanal procedures for wine elaboration and derivatives, its occurrence is increasing. In a patient with symptoms of lead poisoning and regenerative anemia, a peripheral blood smear should be reviewed.

[Detection campaign for hemoglobinopathies and thalassemias among school children in northern Extremadura]. / Campaña de detección de hemoglobinopatías y talasemias en la población escolar del norte de Extremadura.

PURPOSE: To detect carriers of thalassaemia and haemoglobin variants among the northern Extremadura school population. MATERIAL AND METHODS: The study was carried out in the Plasencia health service area, comprising about 120,000 people. All children between 4 and 15 years of age were offered to take part in the programme. The first-stage screen was mean corpuscular volule (MCV) measured in a Coulter STKS automatic counter. When low VCM was detected, ferritin estimation was carried out; if ferritin was normal, hemoglobin A2 was quantified. Haemoglobin electrophoresis at pH 8.4 was performed in all samples whatever the MCV, and patients were classified into the following groups: iron deficiency, beta-thalassaemia, Hb Lepore, structural haemoglobin variant, or atypical microcytosis. RESULTS: Out of 22 schools from 20 towns, 2,818 children were studied, the participation reaching 75.48%. Lower than normal MCV was found in 162 children (5.74%), who were grouped as follows: thalassaemia, 15 cases (0.53%), Hb Lepore, 8 cases (0.28%), iron deficiency, 77 cases (2.73%), atypical microcytosis, 55 cases (1.95%), and structural variants 7 cases (0.24%). These variants were further identified as HbS (3), Hb Hofu (1), in natives, and HbC (3) in children from Morocco. Higher prevalence of anomalies was seen in some places: Riolobos, 1.5%, Galisteo, 2.5%, Jaraiz de la Vera, 3.02%; a significant group of Hb Lepore carriers was detected in this last town. CONCLUSIONS: The prevalence of abnormalities seen in some small towns or villages grants this type of programmes as such places, which could be considered as isolated communities, might provide a number of high-risk couples.

Hb Lepore-Baltimore (delta 68Leu-beta 84Thr) and Hb Lepore-Washington-Boston (delta 87Gln-beta IVS-II-8) in central Portugal and Spanish Alta Extremadura.

Hb Lepore is one of the most common abnormal haemoglobins in Caucasians in Central Portugal and in the Spanish Alta Extremadura (0.28% in a survey of school children). A group of 19 Portuguese and 14 Spanish Hb Lepore carriers (all unrelated) was characterised at the molecular level by the polymerase chain reaction, sequencing and restriction enzyme analysis. The Portuguese and one Spanish carrier were heterozygous for Hb Lepore-Baltimore, whereas all other Spanish subjects were Hb Lepore-Washington-Boston carriers. Sequencing of the Hb Lepore-Baltimore gene further established the crossover at delta 68-beta 84, a region two codons (CDs) shorter than that previously described and easily confirmed by digestion with MaeI and BanI. Data from haplotype analysis suggest that this crossover occurred as an independent event on the Iberian Peninsula. The haematological data were similar in both groups except for the levels of Hb F and the G gamma chain, which were significantly higher in the Hb Lepore-Baltimore heterozygotes. Quantification of the globin chains and the mRNA transcripts showed that the delta beta gene is transcribed at a higher level than the delta gene with levels of translation giving rise to 10%-15% of Hb Lepore. The different levels of Hb F observed in the two groups are the results of the higher transcription rate of the gamma genes in Hb Lepore-Baltimore heterozygotes and an apparently less efficient translation of G gamma genes in Hb Lepore-Washington-Boston heterozygotes.