Mechanisms Underlying Induced Pseudo-Scleroderma among Patients with Phenylketonuria Metabolic Disorder
DOI:
https://doi.org/10.12970/2310-998X.2021.09.01Keywords:
Pseudo-sclerodermas, Phenylalanine metabolic disorder, phenylketonuria (PKU), Dermatological disorders, Phenylalanine hydrolase (PAH), Dihydrobiopterin reductase (DHPR), Current therapeutic advance, Neurological disorder, Melanocytogenesis.Abstract
Pseudo-sclerodermas are neglected dermatological conditions associated with metabolic dysfunction of phenylalanine. Phenylalanine metabolic disorder is an autosomal genetic mutation in phenylalanine hydrolase (PAH). This mutation results in phenylalanine metabolism deficiency and subsequent accumulation of phenylalanine and phenylpyruvic acid in the blood and the cutaneous tissues. The accumulation induces several systemic complications including neurological and dermatological disorders. This report focuses on the mechanisms underlying the induction of the dermatological disorders, current advances in the treatment of phenylketonuria (PKU), and the prospective research areas of interest for the management of dermatological abnormalities in PKU. This metabolic disorder induces chronic bleeding, cellulitis, dermatitis, eczema, psoriasis and parapsoriasis, benign neoplasms of the skin, and melanomas of the skin causing dysregulation of immune cells. The infiltration of CD4+ T-cells and macrophages stimulates IL-4, IL-10, IL-13, and IL-17 leading to the destruction of cutaneous tissues. The insufficiencies of phenylalanine hydroxylase (PAH) and dihydrobiopterin reductase (DHPR) in PKU leads to the accumulation of phenylalanine and phenylpyruvic acid in the corium of the skin. The neurological and psychosocial manifestations of PKU have attracted current advances in therapeutic management targeting the correction of the enzymatic defects in the metabolic pathways or immunoregulation underlying inflammatory conditions to improve the quality of life in PKU patients. However, there is a knowledge gap on the effectiveness of the current therapeutic advance to restore variations in dermatological abnormalities in PKU. Further studies on comorbidities, etiologies, environmental exposures, psychosocial and social effects, and the effects of new therapeutic strategies would provide an insight into the management of pseudo-sclerodermas in PKU disorders.
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