Signs and symptoms
Individuals with A1AD may develop chronic obstructive pulmonary disease (emphysema) during their thirties or forties even without a history of smoking, though smoking greatly increases the risk. Symptoms may include shortness of breath (on exertion and later at rest), wheezing, and sputum production. Symptoms may resemble recurrent respiratory infections or asthma.A1AD may cause several manifestations associated with liver disease, which include impaired liver function and cirrhosis. In newborns, alpha-1 antitrypsin deficiency can result in early onset jaundice followed by prolonged jaundice. Between 3% and 5% of children with ZZ mutations develop life-threatening liver disease, including liver failure. A1AD is a leading reason for liver transplantation in newborns. In newborns and children, A1AD may cause jaundice, poor feeding, poor weight gain, hepatomegaly and splenomegaly. Apart from COPD and chronic liver disease, α1-antitrypsin deficiency has been associated with necrotizing panniculitis (a skin condition) and with granulomatosis with polyangiitis in which inflammation of the blood vessels may affect a number of organs but predominantly the lungs and the kidneys. Genetics
Serpin peptidase inhibitor, clade A, member 1 (SERPINA1) is the gene that encodes the protein alpha-1 antitrypsin. SERPINA1 has been localized to chromosome 14q32. Over 75 mutations of the SERPINA1 gene have been identified, many with clinically significant effects. The most common cause of severe deficiency, PiZ, is a single base-pair substitution leading to a glutamic acid to lysine mutation at position 342 (dbSNP: rs28929474), while PiS is caused by a glutamic acid to valine mutation at position 264 (dbSNP: rs17580). Other rarer forms have been described.
The third symptom would be recovery, followed by a Parkinson-like syndrome. If patients of Stern followed this course of disease, he diagnosed them with encephalitis lethargica. Stern suspected encephalitis lethargica to be close to poliomyelitis, without evidence. Nevertheless, he experimented with the convalescent serum of survivors of the first acute syndrome. He vaccinated patients with early-stage symptoms, telling them that it might be successful. Stern is author of the definitive 1920s book, Die Epidemische Encephalitis.In 2010, in a substantial Oxford University Press compendium reviewing the historic and contemporary views on EL, its editor, Joel Vilensky, of the Indiana University School of Medicine, quotes another researcher, writing in 1930, who states, "we must confess that etiology is still obscure, the causative agent still unknown, the pathological riddle still unsolved…", and goes on to offer the following conclusion, as of that publication date:

Does the present volume solve the "riddle" of EL, which… has been referred to as the greatest medical mystery of the 20th century? Unfortunately, no: but inroads are certainly made here pertaining to diagnosis, pathology, and even treatment." Subsequent to publication of this compendium, an enterovirus was discovered in encephalitis lethargica cases from the epidemic. In 2012, Oliver Sacks, the author of the book Awakenings, about institutionalized survivors, acknowledged this virus as the probable cause of the disease. Other sources have suggested Streptococcus pneumoniae as a cause. Diagnosis
There have been several proposed diagnostic criteria for encephalitis lethargica.