Background <p>Living with children with disabilities has a significant impact on parental health-related quality of life (HRQoL) and family functioning. Barth syndrome (BTHS) is a rare, X-linked disorder that primarily affects males, presenting symptoms such as cardiomyopathy, neutropenia, muscle weakness, and growth delays. In this study, we investigated how a child’s functional performance, family cohesion, and satisfaction with healthcare affect parents of children with BTHS.</p> Methods <p>Thirty-three parents of children with BTHS and 31 parents of age-matched unaffected children participated in this study. The parents completed a series of questionnaires. The Double ABCX model was applied to select measurement variables for this study. An independent samples <i>t</i>-test was used to compare HRQoL and family functioning between the two groups. Regression analysis was conducted to determine how a child’s functional performance, family cohesion, and satisfaction with healthcare affect HRQoL and family functioning of parents of children with BTHS.</p> Results <p>The HRQoL and family functioning of parents of children with BTHS were significantly lower than those of unaffected children (<i>p</i> &lt;.05). In the regression analysis, the child’s functional performance was a significant predictor of HRQoL and family functioning (<i>F</i>(3, 32) = 6.047, <i>p</i> =.003) for parents of children with BTHS.</p> Conclusions <p>This study lays the groundwork for examining the impact of raising children with BTHS on parents and families. It is crucial for health professionals to understand the clinical features of BTHS and to consider not only the child but also the family in order to address their unmet needs and provide holistic healthcare services.</p>