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Background: Measles incidence in the 53 Member States of the World Health Organization (WHO) European Region has fallen dramatically in recent decades. The European Regional Verification Commission for Measles and Rubella Elimination (RVC) verified that 43 member states had interrupted endemic measles transmission for ≥12 months by the end of 2017. However, measles incidence in the region increased sharply in 2018 compared to 2017. The purpose of this article is to assess the current status of measles in the Region in relation to its elimination goal. It also discusses challenges and actions needed to reach this goal., Methods: Measles surveillance data presented for 2017 and 2018 (as of 1 February 2019) were submitted by all 53 member states. The measles elimination status of countries was obtained from the 2018 report of the seventh meeting of the RVC., Results: In 2017, 25,863 measles cases were reported in 44 countries of the WHO European Region. In 2018, 82,596 measles cases were reported in 47 countries. Most cases were reported by Ukraine (64%) and Serbia (6%). Age was known in 82,588 cases: 8% were <1 year old, 17% were 1-4 years old, 38% were 5-19 years old and 37% were ≥20 years old. Data on vaccination status were provided for 76% of the cases, of which 62% were unvaccinated. Seventy-two measles-related deaths were reported from 10 countries., Conclusions: For the elimination of measles in the European Region, a high population immunity rate and accurate epidemiological surveillance remain essential. Long-term political commitment by all Member States in these areas is crucial to attain the elimination goal.

Malignant hyperthermia (MH) is a potentially fatal, inherited pharmacogenetic disorder characterised by a dysfunction of the intracellular calcium regulation. Linkage to DNA markers from the chromosome 19q12-13.2 region and the MHS-phenotype (MH susceptible) has been shown in about 50% of families with a history of MH. The ryanodine receptor gene encoding the human skeletal muscle ryanodine receptor has been localised to the chromosome 19q13.1-13.2 region. The ryanodine receptor, which is an intracellular calcium release channel, has been proposed to be one of the candidate structures for the MH defect. At present, eight different single point mutations have been identified in the human skeletal muscle ryanodine receptor gene in families with disposition to MH. The incidence of the various mutations has been reported as 2-10% each. A combination of different mutations within one pedigree has not been demonstrated. A few years ago, linkage of the MHS-phenotype to DNA markers from the chromosome 17q11.2-24 region was published by an American group. However, this observation has not been confirmed in any of the several European families susceptible to MH. Genes encoding for subunits of the dihydropyridine receptor and the sodium channel of the human skeletal muscle have been found to be located in the chromosome 17q11.2-24 region which, in fact, could be additional candidates for the MH defect. The dihydropyridine receptor is linked to the ryanodine receptor and involved in the calcium regulation of skeletal muscle. Very recent studies have shown linkage to DNA markers from chromosome 7q- and chromosome 3q13.1 regions and the MHS phenotype in two distinct families with history of MH. However, the relevance of this observation is so far unknown. At present, unambiguous preoperative screening of MH disposition based on molecular genetic characteristics is not available because of the enormous heterogeneity of the human MH syndrome. Thus, the halothane-caffeine in-vitro contracture test according to the standard protocol of the "European MH Group" must be performed in order to discover MH susceptibility.

We are reporting a girl aged eight years with ketotic hypoglycemia, mental deficiency and retarded motor and somatic development. Investigation of plasma amino acid concentrations during a spontaneous hypoglycemia revealed an increase in the branched-chain amino acids valine (4.1), leucine (7.8) and isoleucine (1.7 mg/100 ml), while alanine was decreased (1.2 mg/100 ml) and ketonuria was present. The determination of the branched-chain ketoacid decarboxylase in leukocytes showed a decrease of approximately 50% of normal for alpha-ketoisocaproic acid (KIC) as substrate, whereas values for alpha-ketoisovaleric acid (KIVA) and alpha-keto-beta-methylvaleric acid (MEVA) were normal. In fibroblasts activities for all three substrates were in the normal range. Intermittend maple-syrup-urine disease was excluded by oral loading tests with the branched-chain amino acids and with an isocaloric, high-protein diet. Impairment of oxydative decarboxylation of leucine, valine, and isoleucine secondary to increased ketogenesis may play an etiologic role in ketotic hypoglycemia, since we observed, by gaschromatographic analysis, an increase in the urinary excretion of KIVA (5.5 mumol/h), KIC (29.4), and MEVA (47.9) after a provocative test with an isocaloric ketogenic diet for 36 hrs. The significance of branched-chain hyperaminoacidemia and branched chain alpha-ketoaciduria is discussed in this context.

In a family study with two patients showing hyperuricaemia, discrete neurological symptoms, as well as gouty arthritis in the older proband, hypoxanthine phosphoribosyl transferase (HPRT) and adenine phosphoribosyl transferase (APRT) were determined in haemolysates and fibroblast extracts. 6 normal subjects and 3 patients with the Lesch-Nyhan syndrome were examined as controls. Reduced HPRT activity by 18% and 12% in the proband and his nephew, respectively, together with an increase to values of 206% and 113% in APRT activity was observed in haemolysates. In fibroblasts the HPRT activity was reduced to 40--43%, but the APRT activity was within the normal range. The studies indicate the presence of a possible variant form of HPRT in these patients.