Barth syndrome in a female patient
Highlights
► First case of Barth syndrome in a female patient with mosaic ring X.
Introduction
Barth syndrome (BTHS, MIM#302060) is an X-linked recessive disorder firstly described in 1983 and characterized by cardiomyopathy, skeletal myopathy, neutropenia, growth delay, increased urinary excretion of 3-methylglutaconic acid and respiratory chain dysfunction in male patients [[1], [2], [3]]. It is caused by mutations in the TAZ gene, located at Xq28 and coding for tafazzin, a protein involved in the remodeling of cardiolipin [[4], [5], [6], [7], [8]]. Until now, more than 150 mutations in the TAZ gene have been identified, mainly point mutations. Loss of cardiolipin in the inner mitochondrial membrane results in respiratory chain dysfunction, most specifically of complexes I, III and IV [2], [7], [9]. Recently, a mouse model of human BTHS confirmed the pathophysiological relationship between altered mitochondrial phospholipids, myocardial and mitochondrial dysfunction and the clinical outcome [10]. Male patients present cardiomyopathy, mainly of the dilated type, during the first year of life, associated with cardiac arrhythmias or abnormal electrocardiogram patterns for most of them [2], [3]. Growth deficiency, muscle weakness and increased exertional fatigue are also reported later in the clinical course. Neutropenia and low levels of plasma cholesterol have been noted in some patients. Survival rate indicates high mortality in infancy and childhood, even if early diagnosis and rigorous treatment of infections and cardiomyopathy may have contributed to improve the prognosis [2]. In contrast, no specific symptom has been identified in female carriers. We report the case of a girl with a severe clinical phenotype compatible with the diagnosis of BTHS, further confirmed by TAZ gene analysis.
Section snippets
Patient
This girl, first child of unrelated healthy parents with no family history, was born at full term after uneventful pregnancy and delivery, except for intrauterine growth retardation (birth weight 2530 g, height 46 cm, and head circumference 32 cm, all below the third percentile). During the first weeks of life, she had feeding difficulties associated with a progressive polypnea. At one month of age, she was admitted to intensive care unit for severe acute heart failure. Physical examination
Discussion
BTHS is an X-linked recessive disorder caused by mutations in the TAZ gene, located at Xq28, and coding for tafazzin, a protein involved in the remodeling of cardiolipin. BTHS affects male patients, whereas female carriers are usually non-symptomatic [2], [3]. We report the first case of a girl with a severe clinical phenotype in keeping with the diagnosis of BTHS, further confirmed by TAZ gene analysis.
This girl presented many similarities with the clinical and biochemical features of BTHS
Acknowledgments
We are grateful to Philippe Reuge and Wolfgang Berger (Institute of Medical Genetics, University Hospital, Zurich, Switzerland) for their contribution to the molecular analysis of the TAZ gene.
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FGF21 and GDF15 are elevated in Barth Syndrome and are correlated to important clinical measures
2023, Molecular Genetics and MetabolismTAZ encodes tafazzin, a transacylase essential for cardiolipin formation and central to the etiology of Barth syndrome
2020, GeneCitation Excerpt :Characterized initially by Barth et al. in 1983 (Barth et al., 1983) as a uniformly lethal disease that affects only males, it has now been found that the age distribution ranges between 0 and 49 years, and symptoms peak around puberty (Barth et al., 2004). At least one female patient with BTHS has been identified (Cosson et al., 2012). The Barth Syndrome Foundation reports that 151 living Barth patients have been identified up to 2012 and 10 new patients are diagnosed each year in the United States with no apparent racial or ethnic predilections.
A Bayesian Analysis to Determine the Prevalence of Barth Syndrome in the Pediatric Population
2020, Journal of PediatricsCitation Excerpt :Cardiomyopathy and neutropenia are often the most serious symptoms experienced by individuals with Barth syndrome, and we consider them markers of the disease for this analysis. Because this is an X-linked disease, the disease presents almost always in male patients, but there are reports of female cases.14,15 Nevertheless, in this report we focused on cardiomyopathy and neutropenia in the male population for our estimates.
Acquired noncompaction in Barth syndrome due to the TAZ mutation c.481_482ins20
2017, Journal of PediatricsLeft Ventricular Noncompaction Cardiomyopathy
2017, Cardioskeletal Myopathies in Children and Young AdultsLeft ventricular non-compaction cardiomyopathy
2015, The LancetCitation Excerpt :Inheritance of LVNC is most often X-linked recessive or autosomal dominant, although autosomal recessive and mitochondrial (maternal) inheritance also occur.10,14,30,79 X-linked LVNC, which is usually associated with the multisystem disorder Barth syndrome (caused by a mutation in the TAZ gene), affects men almost exclusively, although a woman with cardiomyopathy has been described.80 When LVNC is associated with congenital heart disease, the congenital cardiac defect might be heterogeneous; this type of LVNC is transmitted as an autosomal dominant trait along with the congenital heart abnormality.10