In the near future, the burden of CD will increase tremendously. Few Mediterranean countries are able to face this expanding epidemic alone.

There have been very few reports dealing with liver failure related to hepatitis A in children. Moreover, the criteria usually used for selecting patients with fulminant hepatitis A for liver transplantation have not been evaluated in children. Therefore, the current study was conducted retrospectively in a single French urban pediatric liver transplantation center to serve as a reminder of the potential severity of hepatitis A in children and to identify predictors of outcome. Children were selected by chart review using a data base system and were grouped according to outcome for analyses purposes. Over a 15-year period, 24 children with hepatitis A showed evidence of liver failure, including 6 children who did not develop hepatic encephalopathy, 7 children in whom encephalopathy occurred but resolved spontaneously, and 11 children in whom death or liver transplantation was the outcome. The mean age at onset was 6.5 years. Those with the most rapid onset of liver failure from onset of jaundice had the best chance of recovery without developing encephalopathy. Otherwise, no predictive factors of outcome were found at onset of liver failure. Among the 18 children who developed encephalopathy, the best early prognostic indicator of a poor outcome irrespective of the grade of encephalopathy, appeared to be a prothrombin time level below 21% of normal combined with a serum bilirubin level above 400 micromol/L. Therefore, these two prognostic indicators may be helpful in deciding liver transplantation in children with hepatitis A-induced fulminant liver failure.

Gaucher disease (GD) is a lysosomal storage disorder that responds well to enzyme replacement therapy (ERT). Certain laboratory parameters, including blood concentration of glucosylsphingosine (Lyso-Gb1), the lyso-derivate of the common glycolipid glucocerebroside, correlate with clinical improvement and are therefore considered candidate-monitoring biomarkers. Whether they can indicate a reduction or loss of treatment efficiency, however, has not been systematically addressed for obvious reasons. We established and validated measurement of Lyso-Gb1 from dried blood spots (DBSs) by mass spectrometry. We then characterized the assay’s longitudinal performance in 19 stably ERT-treated GD patients by dense monitoring over a 3-year period. The observed level of fluctuation was accounted for in the subsequent development of a unifying data normalization concept. The resulting approach was eventually applied to data from Lyso-Gb1 measurements after an involuntary treatment break for all 19 patients. It enabled separation of the “under treatment” versus “not under treatment” conditions with high sensitivity and specificity. We conclude that Lyso-Gb1 determination from DBSs indicates treatment issues already at an early stage before clinical consequences arise. In addition to its previously shown diagnostic utility, Lyso-Gb1 thereby qualifies as a monitoring biomarker in GD patients.

Gaucher disease (GD) is a lysosomal storage disorder that is associated with bi-allelic pathogenic variants in GBA. Its wide clinical spectrum, ranging from mild organomegaly to significant skeletal and neurological involvement, is partially explained by genotype-phenotype correlations. We present a family, in which all members over two generations presented with at least splenomegaly. Comprehensive clinical, biochemical and genetic workup was required to diagnose GD, which is caused by as many as four distinct GBA genotypes.

Gaucher disease (GD) is a recessive metabolic disorder caused by a deficiency of the GBA gene-encoded enzyme β-glucocerebrosidase. We characterized a cohort of 36 Albanian GD patients, 31 with GD type 1 and 5 affected by GD types 2, 3, and an intermediate GD phenotype between type 2 and type 3. Of the 12 different GBA alleles that we detected, the most frequently observed was p.Asn409Ser, followed by p.[Asp448His;His294Gln]. The prevalence of the p.Leu483Pro allele was approximately 10-fold lower than reported in other populations. We identified a novel pathogenic missense variant (c.1129G>A; p.Ala377Thr). All five of our non-type 1 patients had genotypes consisting of the p.[Asp448His;His294Gln] allele in combination with another severe GBA allele. The median Lyso-Gb1 level of treated patients carrying the p.[Asp448His;His294Gln] and no p.Asn409Ser allele was significantly higher than that of treated individuals homozygous or compound heterozygous for the p.Asn409Ser allele. In conclusion, the most important distinguishing features of the Albanian GD patient population are the underrepresentation of the p.Leu483Pro allele and an unusually high number of p.[Asp448His;His294-Gln] alleles originating from a common Balkan founder event. The presence of at least one p.Asn409Ser allele is associated with mild disease and low Lyso-Gb1 biomarker levels, while compound heterozygosity involving p.[Asp448His;His294Gln] and no p.Asn409Ser entails severe phenotypes and high Lyso-Gb1 levels.