Wrinkly skin syndrome
[1] The disorder exhibits an autosomal recessive inheritance pattern with mutations in the ATP6V0A2 gene, leading to abnormal glycosylation events.
[1] Some skin symptoms recede with increasing age, while progressive neurological advancement of the disorder causes seizures and mental deterioration later in life for some patients.
[1] Microscopic analysis of epidermal samples of a four-month-old with WSS revealed an irregular pattern of elastic fiber distribution.
[5] Vacuolar ATPases (V-ATPase) regulate the pH of the subcellular compartments found within the endosomal membrane system.
The V1 domain catalyzes the hydrolysis of ATP to power the pumping of protons through the V0 channel, which spans the lipid bilayer of endosomal compartments.
The ATP6V0A2 pump is found in virtually all cells and is thought to play an important role in the process of vesicular fusion in the secretory pathway, including the secretion of extracellular matrix components.
The Golgi apparatus is an important part of the endomembrane system because it processes proteins and lipids prior to their delivery to the plasma membrane and/or secretion into the extracellular environment.
Proteins destined for secretion or delivery to the plasma membrane arrive first at the cis-Golgi, before being trafficked through the medial and trans-Golgi.
In the context of WSS, the most significant PTM events are the glycosylation of proteins comprising the extracellular matrix (ECM) of epidermal cells.
WSS is characterized by defects in the elastic fiber system that comprises the extracellular matrix of epidermal cells.
[6] The skin's elastic fiber system consists of elastin (which is normally non-glycosylated) and glycosylated proteins (fibulin, fibronectin, and collagen).
[9] It is thought that increased pH levels (lower acidity) lead to the premature aggregation (coacervation) of tropoelastin inside the vesicle.
[9] However, it is believed that abnormal/impaired secretion of the brain and bone-specific ECM proteins caused by dysregulation of Golgi acidification is what leads to the neural and skeletal defects in ARCL2.
[10] In addition to assessment of clinical physical symptoms, diagnosis may be aided by:[citation needed] The pigmentation patterns observed in skin biopsies reveal a characteristic lack of elastic fibers in the papillary dermis and clumping of elastic fibers in the reticular dermis.
[10] Despite assessment of each of these diagnostic factors, a definitive diagnosis differentiating WSS from cutis laxa requires genetic testing.
[3] Therapeutic treatment options include physical therapy to improve muscular development while patient growth and osteoporosis can be monitored via developmental assessments and bone density scans, respectively.
Due to therapeutic interventions for developmental symptoms, long-term outcomes are improved by diagnosis of the disorder during childhood.
[16] In 2008, Kornak et al. investigated glycosylation of serum proteins with individuals with WSS and found that they had defects in N-glycosylation at the level of the Golgi apparatus.
