Alpha-1 antitrypsin (AAT) is the most abundant irreversible serine proteinase inhibitor in the circulation and plays a major role in protecting lung tissue against destruction from neutrophil serine proteinases. Genetic mutation of AAT leads to reduced circulating levels and AAT deficiency (AATD) which is associated with an increased risk of developing emphysema. This observation suggests that the balance between AAT and neutrophil serine proteinase is crucial in maintaining tissue homoeostasis. In AATD, the overexuberant proteinase activity resulting from inadequate AAT control creates a self-perpetuating inflammatory cycle, driving progressive tissue injury. Re-establishing this physiological balance is therefore critical for preserving lung architecture, function, and abrogating disease progression.

Several avenues within this pathophysiological pathway are being explored. This chapter addresses the pathophysiological process, current treatments targeting the pathway, and alternative approaches within the pathway that can potentially mitigate proteinase imbalance.

Aim: This research assessed the needs of family caregivers of children with cerebral adrenoleukodystrophy (cALD), focusing on the diagnostic process; the burden of the disease on the child and their caregiver’s quality of life; and the physical, social, psychological, professional, and financial impacts on the whole family.

Methods: Family caregivers of children with cALD were recruited via the European Leukodystrophies Association International’s online platform, Leuconnect, to respond to a quantitative survey and a quality-of-life questionnaire and participate in a qualitative semi-structured interview. The questions focused on disease experience from onset to diagnosis and consequences on current life. Twelve family caregivers of 14 children were interviewed.

Results: cALD diagnosis took an average of 16.5 months, and 8 of 12 children were misdiagnosed, with parents often describing a lack of listening from doctors. Caregivers described bedridden children whose poor quality of life correlated with a high Neurologic Function Score. On average, they needed to care for their children 7.7 h/day, with serious consequences for their employment, social life, and psychological state.

Conclusion: Our interviews with family caregivers helped us to consider limiting diagnostic wandering by improving the skills of general practitioners and public knowledge of pathology. By gathering information on precise daily routines centered around a dependent child, we can better understand how to effectively support families by adapting not only the global care of the child but also to the following needs expressed for the entire family: better information, coordination of both care and administrative procedures, and real respite.