HGPS and PL: Premature aging diseases
HGPS and PL, collectively known as progeria, are ultra-rare genetic diseases of premature aging. They are distinct illnesses but are often grouped together as types of laminopathies that result in accelerated morbidity and mortality.1,2,3
Similarities of HGPS and PL:
Low prevalence rates
Both diseases are extremely rare. The worldwide prevalence of HGPS is 1 in 20 million, while other progeroid laminopathies, of which PL is only a subset, have a prevalence of 1 in 36.4 million.1,4
Shared disease pathophysiology processes
Both diseases are caused by genetic mutations that affect the same nuclear architecture pathway. These mutations lead to the accumulation of harmful proteins that damage the cells, resulting in early mortality.1
Accelerated morbidity and mortality
Cardiovascular manifestations are commonly seen through the course of disease, although select manifestations and severity can vary between HGPS and PL. In HGPS, patients often experience progressive atherosclerosis leading to cardiovascular disease, stroke and early mortality, primarily caused by heart failure, at a mean age of 14.6 years if untreated.2,5
Did you know?
Patients with HGPS age 8 to 10 times faster than normal.3
The underlying cause of HGPS and PL
HGPS and PL are caused by mutations that lead to the accumulation of harmful proteins in the nuclear membrane.1
HGPS is caused by single-base pathogenic variants of the LMNA gene; LMNA codes for lamin A, an inner nuclear membrane protein that is crucial to many cellular functions. In HGPS, the mutant gene results in an enzymatically modified form of lamin A called progerin.1
Progeroid laminopathies are caused by a range of genetic mutations within the same cellular pathway, ultimately resulting in the accumulation of progerin-like proteins.2
The accumulation of progerin or progerin-like proteins inside the cell nucleus impairs tissue repair functions and further damages cells as they age, leading to early mortality.1
These cellular defects result in morbidities such as failure to thrive, generalised lipodystrophy, alopoecia, bone dysplasia, and progressive atherosclerosis that leads to cardiac disease and stroke.1
The root cause of premature aging in HGPS and PL is the enzymatic modification of prelamin A or a downstream protein.1
Early diagnosis of progeria allows for earlier, targeted intervention
Children appear normal at birth but start to develop symptoms during the first 12 to 18 months of life.
Clinical evaluation of a child’s appearance
- Evaluation of height and weight (failure to thrive, typically during first year of life)
- Examination for distinct visible clinical features
- Assessment of vital signs
Medical history and records
- Evidence of vascular dysfunction; early cardiac changes can manifest between 5 and 8 years of age, usually start after age 8
Genetic testing to detect LMNA or ZMPSTE24 mutations
- Consult your physician for genetic testing information in your location