What is Alpha1 Antitrypsin Deficiency

Alpha1 Antitrypsin provides antiprotease protective screens throughout the entire body, not just the lungs!

Alpha1 Antitrypsin Deficiency can be many things, and defining it can be tricky because of so many variations in defining precisely what it is. Many define Alpha1 Antitrypsin as having specific alleles. Therefore, Alpha1 Antitrypsin Deficiency is a condition that is extremely poorly defined and can lead to misconceptions.

Mark Egly has done extensive research on the condition. Mark is a person who has Alpha1 Antitrypsin Deficiency. The world recognizes the disease as rare, and Mark would instead teach that Alpha1 Antitrypsin Deficiency is a rarely diagnosed disease. Under current definitions, identification, and potential subsequent treatment of AATD needs an additional standard of care to be implemented. Our Foundation is moving forward with new definitions that are less restrictive with respect to patient awareness and care!

What can be defined about Alpha1 Antitrypsin Deficiency is:

It is a genetic disorder involving the SERPINA1 gene
A genetic situation where the SERPINA1 gene do not allow the body to make enough Alpha1 Antitrypsin to protect the body adequately from excess neutrophils and/or
It is a genetic situation in which the person has improperly unfolded Alpha1 Antitrypsin from the liver. This improper unfolding causes potential liver damage and lowers the amount of Alpha1 Antitrypsin capable of protecting the body and its tissue to the best of its ability.

Alpha1 Antitrypsin Deficiency can be described by allele variations, with the M allele typically considered the best allele for high levels of protection. Here is a list of almost all the known alleles at the time of Mark's patent submission.

Known Alleles of the SERPINA1 Gene

Allele	Pathogenic Mutation	Consequence (SIFT and Polyphen scores)
Q0_Faro	c.-5+ 2dupT	AATD: protein absence
I	p.Arg39Cys	AATD: protein deficiency (0.03; 0.591)
M_Malton	p.Phe52del	AATD: protein deficiency (0; 0.99)
M_Palermo	p.Phe52del	AATD: protein deficiency (0; 0.99)
Q0_Lisbon	p.Thr68Ile	AATD: Protein absence (0; 0.98)
P_Gaia	p.Glu162Gly	AATD: protein deficiency (0.01; 0.80)
P_Lowell	p.Asp256Val	AATD: protein deficiency (0; 0.97)
Q0_Gaia	p.Leu263Pro	AATD: protein absence (0; 0.972)
T	p.Glu264Val	AATD: protein deficiency (0; 0.93)
Q0_{Oliveira do Douro}	p.Arg281Lysfs*17	AATD: protein absence
Q0_Ourém	p.Leu353Phefs*24	AATD: protein absence
M_Herleen	p.Pro369Leu	AATD: protein deficiency (0; 0.99)
M_Wurzburg	p. Pro369Ser	AATD: protein deficiency (0; 0.99)
Q0_{Vila Real}	p.Met374Leufs*19	AATD: protein absence
-	p.Pro-23Leu	Possibly damaging (0.03; 0.50)
Z_Wrexham	p.Ser-19Leu	Not linked to AATD (0.05; 0.50)
-	p.Trp-18Cys	Probably damaging (0.01; 0.91)
-	p.Leu-13Met	Probably damaging (0; 0.99)
V_Munich	p.Asp2Ala	Not linked to AATD (0.06; 0.02)
-	p.Pro3Leu	Benign (0.55; 0)
-	p.His15Asn	Benign (0.41; 0)
-	p.His16Arg	Benign (0.13; 0)
-	p.Ala34Ser	Possibly damaging (0.06; 0.61)
M5_Karlsruhe	p.Ala34Thr	Not linked to AATD (0.13; 0.277)
Q0_Knowloon	p.Tyr38Ter	AATD: protein absence
M_Procida	p.Leu41Pro	AATD: protein deficiency (0.19; 0.99)
M_Varallo	p.Leu41-Phe51delfs*20	AATD: protein deficiency
-	p.His43Gln	Benign (0.35; 0.011)
M6_Bonn	p.Ser45Phe	Not linked to AATD (0; 0.867)
-	p.Ser47Arg	Not linked to AATD (0.05; 0.01)
M_Nichinan	p.Phe52del	AATD: protein deficiency (0; 0.99)
S_iiyama	p.Ser53Phe	AATD: protein deficiency (0; 1)
M6_Passau	p.Ala60Thr	Not linked to AATD (0; 0.668)
-	p.Leu66Arg	Probably damaging (002; 0.99)
M_{Mineral Springs}	p.Gly67Glu	AATD: protein deficiency (0:0.99)
-	p.Thr72Ala	Possibly damaging (0; 0.82)
-	p.Leu84Arg	Benign (0.02; 0.10)
Z_Bristol	p.Thr85Met	AATD: protein deficiency (0.02; 0.94)
Q0_Ludwisghafen	p.Ile92Asn	AATD: protein absence (0; 0.96)
Q0_Soest	p.Thr102Profs*10	AATD: protein absence
Q0_Devon	p.Gly115Ser	AATD: protein deficiency (0.1; 0.97)
Q0_Newport	p.Gly115Ser	AATD: protein deficiency (0.1; 0.97)
Z_Newport	p.Gly115Ser	AATD: protein deficiency (0.1; 0.97)
-	p.Leu120Phe	Possibly damaging (0; 0.87)
-	p.Glu122Lys	Benign (0.15; 0.27)
-	p.Lys129Glu	Probably damaging (0.07; 0.91)
-	p.Phe130Leu	Probably damaging (0; 0.99)
-	p.Ala142Asp	Probably damaging (0; 0.98)
V	p.Gly148Arg	Not linked to AATD (1; 0)
M2_Obernburg	p.Gly148Trp	Not linked to AATD (0.01; 0.70)
-	p.Glu151Lys	Benign (0.27; 0.14)
Queen's	p.Lys154Asn	AATD: protein deficiency (0.06; 0.844)
Q0_Chillichote	p.Gln156Ter	AATD: protein absence
Q0_{Granite Falls}	p.Tyr160Ter	AATD: protein absence
Q0_Bredevoort	p.Tyr160Ter	AATD: protein absence
Q0_amersfoort	p.Tyr160Ter	AATD: protein absence
-	p.Val161Met	Probably damaging (0; 0.99)
-	p.Leu172Ser	Probably damaging (0; 0.99)
Q0_Cork	p.Thr180Serfs*11	AATD: protein absence
-	p.Lys193Ter	AATD: protein absence
Q0_Trastevere	p.Trp194Ter	AATD: protein absence
-	p.Pro197His	Probably damaging (0; 0.98)
-	p.Asp207Glu	Benign (0.09; 0.01)
-	p.Val210Met	Possibly damaging (0; 0.86)
-	p.Val216Met	Probably damaging (0; 0.99)
Q0_Bellingham	p.Lys217Ter	AATD: protein absence
F	p.Arg223Cys	Altered function (0.02; 0.52)
-	p.Arg223His	Benign (0.09; 0.33)
P_brescia	Gly225Arg	AATD: protein deficiency (0.01; 0.95)
-	p.Gly225Ala	Probably damaging (0; 0.97)
-	p.Lys233Asn	Benign (0.14; 0)
Q0_Perugia	p.Val239Cysfs*3	AATD: protein absence
P_Duarte	p.Asp256Val	AATD: protein deficiency (0; 0.97)
-	p.Gly258Arg	Probably damaging (0; 0.99)
Q0_Brescia	p.Glu257Ter	AATD: protein absence
M_Pisa	p.Lys259Arg	AATD: protein deficiency (0; 0.958)
Q0_Cairo	p.Lys259Ter	AATD: protein absence
Q0_Milano	p.Lys259-Glu264delTer	AATD: protein absence
-	p.His262Tyr	Benign (0.11; 0.06)
-	p.His269Gln	Benign (0.31; 0.00)
-	p.Leu276Pro	Probably damaging (0.03; 0.92)
-	p.Asn278Ile	Benign (0.31; 0.00)
I_Euskadi	p.Arg281del	Not linked to AATD
-	p.Ala284Ser	Benign (0.02; 0.15)
-	p.Ile293Hisfs*6	AATD: protein absence
Q0_Torino	p.Try297Ter	AATD: protein absence
-	p.Asp298Glu	Benign (0.05; 0.08)
-	p.Val302Ile	Not linked to AATD (1; 0.04)
Q0_Cosenza	p.Gln305Ter	AATD: protein absence
-	p.Gly307Ser	Probably damaging (0; 0.97)
-	p.Val311Ile	Benign (0.29; 0.07)
-	p.Gly315Glu	Benign (1; 0.01)
Q0_{Hong Kong}	p.Leu318Serfs*17	AATD: protein absence
Q0_{New Hope}	p.Gly320Glu	AATD: Protein absence (0; 0.98)
-	p.Gly320Arg	Probably damaging (0.02; 0.99)
-	p.Ala325Pro	Benign (0.26; 0.01)
Q0_Pordenone	p.Leu327Argfs*12	AATD: protein absence
S_Munich	p.Ser330Phe	Not linked to AATD (0; 0.89)
-	p.Val333Met	Possibly damaging (0.08:0.53)
King's	p.His334Asp	AATD: protein deficiency (0.02; 0.943)
-	p.Lys335Glu	Possibly damaging (0; 0.56)
W_Bethesda	p.Ala336Thr	AATD: protein deficiency (60%) (0; 0.93)
-	p.Val337Gly	Probably damaging (0; 0.99)
-	p.Val337Valfs*2	AATD: protein absence
-	p.Asp341Glu	Possibly damaging (0.03; 0.66)
P_donauworth	p.Asp341Asn	Not linked to AATD (0.06; 0.44)
P_{Saint albans}	p.Asp341Asn	Not linked to AATD (0.06; 0.44)
Z_Augsburg	p.Glu342Lys	AATD: protein deficiency (0.07; 0.99)
-	p.Gly344Glu	Probably damaging (0.08; 0.99)
Q0_Mattawa	p.Leu353Phefs*24	AATD: protein absence
M_Pittsburgh	p.Met358Arg	Altered function (0.24; 0.00)
-	p.Met358Ile	Likely Altered function (0.25; 0.00)
L_Offenbach	p.Pro362Thr	Not linked to AATD (0; 0.10)
São Tomé	p.Pro362His	Not linked to AATD (0.04; 0.289)
Q0_Bolton	p.Pro362Argfs*12	AATD: protein absence
Q0_Clayton	p.Pro362Profs*15	AATD: protein absence
Q0_Saarbruecken	p.Pro362Profs*15	AATD: protein absence
X_Christchurch	p.Glu363Lys	Not linked to AATD (0.74; 0.192)
E_Taurisamo	p.Lys368Glu	AATD: protein deficiency (0.01:0.083)
Q0_Dublin	p.Phe370Leufs*4	AATD: protein absence
-	p.Ile375Val	Benign (0.4; 0.00)
-	p.Met385Val	Benign (1; 0.01)
Y_Barcelona	p.Pro391His	AATD: protein deficiency (0; 1)
Y_orzinuovi	p.Pro391His	AATD: protein deficiency (0; 1)
Q0_{Isola di Procida}	Del 17 Kb including exons II-V	AATD: protein absence
Q0_Riedenburg	SERPINA1 deletion	AATD: protein absence
Q0_Savannah	g.5307_5308ins8bp	AATD: protein absence
Q0_Porto	c.-5 + 1G > A	AATD: protein absence
Q0_Madrid	c.-5+ 2dupT	-
Q0_{Bonny blue}	c.-4+1Gdel	AATD: protein absence
Q0_West	c.-4+1G>T	AATD: protein absence

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What is Alpha1 Antitrypsin Deficiency

Known Alleles of the SERPINA1 Gene