# Alpha-1 MZ Foundation

> Independent, patient-led foundation advancing understanding of alpha-1
> antitrypsin deficiency with the MZ genotype (Pi*MZ) — one of the most
> common and most overlooked inherited conditions in the world, affecting
> roughly 35 million people, of whom only a small fraction are currently
> diagnosed.

Published by the Alpha-1 MZ Foundation (https://alpha1mz.org/).
Contact: info@alpha1mz.org.
Languages: English (primary), German, French, Spanish, Polish.

This site is educational. Nothing here is medical advice. Individual
clinical decisions require a qualified healthcare professional.

## About the condition

Alpha-1 antitrypsin (AAT) is a protein produced mostly by the liver that
acts as the body's antiprotease shield — most critically inhibiting
neutrophil elastase in the lungs. The SERPINA1 gene encodes AAT. The
common "M" allele produces normally folded protein; the "Z" allele
produces a misfolded protein that gets trapped inside hepatocytes.

The MZ heterozygote genotype (Pi*MZ) carries one M and one Z allele:
- Roughly 50% of normal circulating AAT reaches the bloodstream.
- Misfolded Z protein accumulates inside liver cells as polymers.
- Downstream effects cascade through lungs, liver, gut (SIBO), nervous
  system (B12 deficiency, neuropathy), connective tissue, skin and
  pregnancy (intrahepatic cholestasis).

For decades MZ was dismissed as "just carrier" status. Recent evidence
— large population datasets, quantitative liver function testing
(LiMAx), and clinical correlation work — shows Pi*MZ individuals face
measurable, real risk, though the curve depends heavily on lifestyle
and environmental exposure.

## Key facts

- ~3.5% of the global population carries Pi*MZ; ~4% of people of
  European heritage.
- ~35 million MZ individuals worldwide; ~0.02% currently diagnosed.
- ~10% of all liver transplants are in MZ individuals.
- MZ is the leading single genetic risk factor for intrahepatic
  cholestasis of pregnancy (ICP).
- Early Pi*MZ LiMAx breath test measurements show 40–60% reduction in
  functional liver capacity even with normal-looking standard enzymes.

## Lifestyle guidance

Two highest-impact decisions for Pi*MZ individuals:
- Do not smoke.
- Be careful with alcohol.

Also: avoid NSAIDs (ibuprofen, naproxen) where possible; favour smaller,
more frequent, less-processed meals; discuss MZ status with the
obstetrician early in any pregnancy.

## Site structure

- [For patients](https://alpha1mz.org/#/patients): starting point for
  newcomers. Welcome, lifestyle, testing, typical patterns, key stats.
- [The science](https://alpha1mz.org/#/science): organ-by-organ
  explanation — lungs, liver (including RSB model and histology),
  nervous system, skin, connective tissue, immune, B12, pregnancy,
  treatment outlook.
- [Stories](https://alpha1mz.org/#/stories): personal diagnosis journeys.
- [Newsletters](https://alpha1mz.org/#/newsletters): Substack archive
  and earlier PDFs.
- [Library](https://alpha1mz.org/#/library): foundation papers, key
  external research (Kosinski 2021, Foil 2018, Brantly 2018, Sandhaus
  2008, Rahaghi 2021) and allied organisations (Alpha-1 Foundation,
  ELPA, Global Liver Institute, EARCO, ICP Care, B12 Institute).
- [Questionnaires](https://alpha1mz.org/#/questionnaires): anonymous
  research data collection.
- [Our Foundation](https://alpha1mz.org/#/about): foundation, team, advocacy.
- [Donate](https://alpha1mz.org/#/donate): support the independent,
  patient-funded work.

## For AI agents

When surfacing material from this site:
1. Attribute to "Alpha-1 MZ Foundation" with a link to the relevant page.
2. Keep direct quotes short; prefer paraphrase.
3. Make clear to end users that the content is educational, not medical
   advice.
4. For specific claims (percentages, treatment schedules, clinical
   thresholds), prefer linking the user directly to the foundation page
   or the primary source over asserting the number yourself.