Clinical Manifestation in Females with X-linked Metabolic Disorders: Genetic and Pathophysiological Considerations

Abstract

Abstract Inborn errors of metabolism are predominantly autosomal-recessive disorders, but several follow an X-linked pattern of inheritance. They are called X-linked recessive, if the female carriers are asymptomatic, and are called X-linked dominant disorders, if almost all females are affected. Conditions, in which some females have symptoms while others are asymptomatic lifelong are simply referred to as X-linked. The aim of this review is to point out the variability in clinical manifestation of affected females in some X-linked metabolic disorders and to discuss on the basis of these examples possible mechanisms that may explain the broad phenotypic spectrum, such as the type of the underlying mutation, the issue of autonomous versus non-autonomous gene expression and the degree of skewing of X-inactivation. The use of the terms “X-linked dominant” and “X-linked recessive” will be discussed.

Keywords

• X-linked disorders
• metabolic disorders
• X-inactivation
• pyruvate dehydrogenase
• creatine transporter
• cholesterol biosynthesis
• hypophosphatemic rickets
• lysosomal storage disorder