During the last few years, clinical, epidemiological, and pathological
evidence has suggested that inherited alpha-1 antitrypsin [AAT] deficiency might play a role in the development of the fibromyalgia syndrome [FMS], probably because of the loss of AAT anti-inflammatory
efficacy. The objective of this study was to estimate the prevalence and number of
FMS patients, and their AAT phenotypic distribution worldwide. Methods: A critical review selecting
reliable studies on the subject.
Results: Studies on AAT gene frequencies and FMS prevalence were retrieved for ten countries
worldwide, namely Canada, the United States of America [USA], Denmark, Finland, Germany, Italy,
the Netherlands, Spain, Sweden, and Pakistan. The severe deficiency Z allele was found in all
these countries, with very high frequencies in Denmark and Sweden [23 and 27 per 1,000, respectively],
high frequencies in Italy and Spain [16 and 17], intermediate frequencies in Germany, the
Netherlands, Canada, and the USA [10 to 14], and a low frequency in Pakistan [nine per 1,000].
The calculated prevalence of AAT deficiency and the number of FMS patients with AAT deficiency
were 1/10 and 25,408 in Canada, 1/11 and 478,681 in the US, 1/9 and 3,124 in Denmark, 1/
36 and 726 in Finland, 1/16 and 48,523 in Germany, 1/13 and 84,876 in Italy, 1/15 and 9,639 in the
Netherlands, 1/4 and 114,359 in Spain, 1/11 and 9,065 in Sweden, and 1/25 and 85,965 in Pakistan.
Our calculations predict that AAT deficiency would remain undetected in around nine percent of
FMS patients, with about eight percent of them carrying moderate deficiency phenotypes [MS, SS,
and MZ], and less than one percent with severe deficiency phenotypes [SZ and ZZ].
Conclusions: Therefore, AAT phenotype characterization should be recommended in FMS patients
and the possible efficacy of AAT replacement therapy in severe deficiency FMS patients
should warrant further studie
