The overall prevalence of LSDs in the Czech population (12.25 per 100,000), which represents a typical Central European population, is comparable to prevalences reported for Australia (12.9 per 100,000), the Netherlands (14 per 100,000) and Italy (12.1 per 100,000) (Meikle et al. 1999
; Poorthuis et al. 1999
; Dionisi-Vici et al. 2002
). The higher prevalence of LSDs reported for the northern Portuguese population (25 per 100,000) might reflect the relative geographic isolation and more extensive studying of that particular population of this region (Pinto et al. 2004
). The most frequent single LSD is Gaucher disease in the Czech Republic, Italy and Australia, GM2 gangliosidosis in Portugal, and Pompe disease in the Netherlands.
In the Czech population, lipidoses were most frequently diagnosed (5.0 per 100,000 live births), followed by MPS (3.72) and NCL (2.29). In addition to the LSD diagnoses in Czech patients, 96 cases from Slovakia were confirmed at our Institute during the studied period; 41% with lipidoses, 39% with MPS, and 20% with GSD II or NCLs. These Slovakian patients have not been included in our prevalence calculations as former Czechoslovakia was divided into two independent states, the Czech Republic and the Slovak Republic, in 1993. Interestingly, the four cases of prosaposin deficiency so far diagnosed at our Institute came from neighboring populations (Slovak, German) (Hulkova et al. 2001
; Elleder et al. 2005
; Kuchar et al. 2009
The birth prevalence of the most frequent LSD in the Czech Republic, Gaucher disease, is 1.13 per 100,000 live births, followed by Niemann-Pick C (0.91), MPS III (0.91), MPS IV (0.73), and MPS I (0.72). Comparison of these prevalences to those in selected foreign populations (Tables , and ) is complicated by the differences in methods used for calculation. When we compared the calculations of prevalence in the Czech population based on the method of Poorthuis et al. (1999
) used in this study (see “Patients and Methods
”) to the method reported by Meikle et al. (1999
) (the prevalence calculated as the number of patients divided by the total number of live births during the study period), the calculations resulted in underestimation or overestimations of some individual disorders. This is the case for disorders with delayed onset (e.g., frequencies of Fabry disease were 0.52 and 1.14 per 100,000, and frequencies of cholesterol ester storage disease were 0.27 and 0.42, if calculated using the methods of Poorthuis et al. (1999
) and Meikle et al. (1999
), respectively). Also, unavailability of some diagnostic methods during the study period (some methods were introduced as late as the 1990s) may explain some discrepancies found in our calculations using the two methods. Although prevalence values for some disorders calculated using either of the methods were within the confidence intervals (data not shown), for other disorders prevalence values fell outside this interval (e.g., the frequencies differed for MPS III C (0.42 and 0.11 per 100,000), MPS IVA (0.71 and 0.32), NCL 2 (0.36 and 0.65) and NCL 7 (0.85 and 0.42), if calculated according to the methods used by Poorthuis et al. (1999
) and Meikle et al. (1999
Thus, establishment of standard rules for calculation of birth prevalence-a defined term in clinical epidemiology-is highly recommended. This would enable more reliable comparison of data from different populations. Based on our experience, the calculation of the ratio of the number of patients to the number of live births during the patients’ births period (Poorthuis et al. 1999
) fits well to the definition of prevalence. Underestimation of the birth prevalence may result from lack of recognition of early clinical signs and symptoms or phenotypic diversity, including adult forms of the disease (e.g., Fabry disease, adult Krabbe disease, adult MLD, cholesteryl ester storage disease, and adult GSD II). Thus, the calculated birth prevalence is probably the lowest estimate as the diagnosis is commonly delayed for years. Screening studies have shown that certain groups of patients, for example individuals with renal failure on haemodialysis, may harbor missed Fabry patients (Nakao et al. 2003
; Kotanko et al. 2004
). The nationwide screening study among 3,370 chronic haemodialysis patients in the Czech Republic disclosed four previously unrecognized Fabry males and one female from five unrelated families. Subsequent family screening ascertained Fabry disease in another 12 individuals, including 8 females (Merta et al. 2007
). Patients with unexplained cardiomyopathy represent another group at risk of having Fabry disease where screening is justified (Monserrat et al. 2007
). Such LSD screening initiatives for selected LSDs will contribute to the identification of the true prevalence of these disorders (Spada et al. 2006
; Chien et al. 2008
Fabry heterozygotes have not been included in the calculation of birth prevalence in previous reports (Meikle et al. 1999
; Poorthuis et al. 1999
; Pinto et al. 2004
). However, they commonly develop clinical symptoms and severe complications, generally a few years later, as in affected men (Deegan et al. 2006
; Wilcox et al. 2008
). When we included Fabry heterozygotes in the calculations, the prevalence of Fabry disease increased by 2.5 times to 1.29 per 100,000 live births, that of lipidoses from 5.0 to 5.77 per 100,000 and the overall prevalence of LSDs reached 13.02 per 100,000 (Table ). Therefore, we propose that Fabry heterozygotes ought to be included in the calculation of the birth prevalence of Fabry disease.
Reliable calculation of the birth prevalence is dependant on a correctly defined pathogenic cause underlying the condition. Recent molecular studies have provided evidence for at least ten separate genetic loci (CLN1–CLN10) for NCL (Peltonen et al. 2000
; Siintola et al. 2007
). These new findings necessitated reclassification of our 37 cases that had formerly been provisionally classified as NCL6 into NCL5, NCL6, and NCL7 subgroups. The latter turned out to be of high prevalence in the Roma Gypsy population (Kousi et al. 2009
). About a quarter of the NCL cases remain unspecified due to the lack of material suitable for mutation analysis.
Athough specific LSDs are generally reckoned to be rare disorders, as a group of inherited metabolic disorders they are quite common, as seen from published and our data. The information on birth prevalencies of LSDs is available from countries with a long tradition of diagnosis of LSDs; however, for most populations, these date are missing. Epidemiological data on these disorders are important in genetic counselling for calculation of the risk for the disorders in the other members of affected families and subsequently for the public health care systems.
Importantly, awareness of the clinical aspects of these life-threatening and progressively disabling genetic diseases among the medical community should increase, allowing earlier diagnosis. In turn, this will offer an opportunity for early therapeutic intervention. Dependant on the diagnosed disorder, such intervention may include enzyme replacement therapy, bone marrow transplantation, or other current or future therapies. Last but not least, it should be borne in mind that genetic counselling and prenatal diagnosis in families affected by a genetic metabolic disorder still form the basic strategy for lowering the number of patients with these severe disorders.