As such, lung disease and liver disease of A1AT deficiency appear unrelated, and the presence of one does not appear to predict the presence of the other. Between 10 and 15% of people with the PiZZ genotype will develop liver fibrosis or liver cirrhosis, because the A1AT is not secreted properly and therefore accumulates in the liver. The mutant Z form of A1AT protein undergoes inefficient protein folding (a physical process where a protein chain achieves its final conformation). 85 percent of the mutant Z form are unable to be secreted and remain in the hepatocyte. Nearly all liver disease caused by A1AT is due to the PiZZ genotype, although other genotypes involving different combinations of mutated alleles (compound heterozygotes) may also result in liver disease. A liver biopsy in such cases will reveal PAS-positive, diastase-resistant inclusions within hepatocytes. Unlike glycogen and other mucins which are diastase sensitive (i.e., diastase treatment disables PAS staining), A1AT deficient hepatocytes will stain with PAS even after diastase treatment - a state thus referred to as "diastase resistant". The accumulation of these inclusions or globules is the main cause of liver injury in A1AT deficiency. However, not all individuals with PiZZ genotype develop liver disease (incomplete penetrance), despite the presence of accumulated mutated protein in the liver. Therefore, additional factors (environmental, genetic, etc.) likely influence whether liver disease develops. Diagnosis
The gold standard of diagnosis for A1AD consists of blood tests to determine the phenotype of the AAT protein or genotype analysis of DNA.
Hyposmia, or microsmia, is a reduced ability to smell and to detect odors. A related condition is anosmia, in which no odors can be detected. Some of the causes of olfaction problems are allergies, nasal polyps, viral infections and head trauma. In 2012 an estimated 9.8 million people aged 40 and older in the United States had hyposmia and an additional 3.4 million had anosmia/severe hyposmia.Hyposmia might be a very early sign of Parkinsons disease. Hyposmia is also an early and almost universal finding in Alzheimers disease and dementia with Lewy bodies. Lifelong hyposmia could be caused by Kallmann syndrome or Autism Spectrum Disorder. Along with other chemosensory disturbances, hyposmia can be a key indicator of COVID-19. Epidemiology
The National Health and Nutrition Examination Survey (NHANES) collected data on chemosensory function (taste and smell) in a nationally-representative sample of US civilian, non-institutionalized persons in 2012. Olfactory function was assessed on persons aged 40 years and older with an 8-item, odor identification test (Pocket Smell Tests™, Sensonics, Inc., Haddon Heights, NJ). Odors included food odors (strawberry, chocolate, onion, grape), warning odors (natural gas, smoke) and household odors (leather, soap). Olfactory function score was based on the number of correct identifications. Prevalence (%) of anosmia/severe hyposmia (scores 0 to 3) was 0.3 at age 40-49 rising to 14.1 at age 80+. Prevalence of hyposmia (scores 4 to 5) was much higher: 3.7% at age 40-49 and 25.9% at 80+. Both were more prevalent in individuals of African descent than in those of Caucasian descent.