Abstract
BackgroundThis study describes the natural history of Barth syndrome (BTHS).MethodsThe medical records of all patients with BTHS living in France were identified in multiple sources and reviewed.ResultsWe identified 16 BTHS pedigrees that included 22 patients. TAZ mutations were observed in 15 pedigrees. The estimated incidence of BTHS was 1.5 cases per million births (95%CI: 0.2–2.3). The median age at presentation was 3.1 weeks (range, 0–1.4 years), and the median age at last follow-up was 4.75 years (range, 3–15 years). Eleven patients died at a median age of 5.1 months; 9 deaths were related to cardiomyopathy and 2 to sepsis. The 5-year survival rate was 51%, and no deaths were observed in patients ≥3 years. Fourteen patients presented with cardiomyopathy, and cardiomyopathy was documented in 20 during follow-up. Left ventricular systolic function was very poor during the first year of life and tended to normalize over time. Nineteen patients had neutropenia. Metabolic investigations revealed inconstant moderate 3-methylglutaconic aciduria and plasma arginine levels that were reduced or in the low-normal range. Survival correlated with two prognostic factors: severe neutropenia at diagnosis (<0.5 × 109/L) and birth year. Specifically, the survival rate was 70% for patients born after 2000 and 20% for those born before 2000.ConclusionsThis survey found that BTHS outcome was affected by cardiac events and by a risk of infection that was related to neutropenia. Modern management of heart failure and prevention of infection in infancy may improve the survival of patients with BTHS without the need for heart transplantation.
Highlights
This study describes the natural history of Barth syndrome (BTHS)
We asked these sources to identify their patients with known BTHS or patients who presented with dilated cardiomyopathy and neutropenia
Six individuals that were referred as potential BTHS patients in different pedigrees were excluded because of a lack of clinical data
Summary
Demographic data We analysed data from 22 subjects in 16 pedigrees (Additional file 2: Figure S2). During follow-up, a median of 8 CBC values per patient was available (range, 1–46 values). Four patients died during an infectious episode, 2 of septic shock and 2 of cardiac failure associated with high fever without bacterial documentation. One of the oldest patients of the cohort (UPN 7112, age 12.6 years) never showed any clinical signs of cardiomyopathy. Skeletal myopathy and other clinical features The age for walking was available for 8 patients who survived until the age of 2.5 years, and the median age for walking was 19 months (range, 12 –24). The following potential prognostic factors for survival were studied in univariate analysis: heart function parameters at diagnosis (including shortening fraction, ejection fraction and LV mass), neutrophil count, platelet count, haemoglobin levels at diagnosis, birth weight and the year of birth (before vs in or after 2000). When these two prognostic factors were analysed together in a Cox model, they both remained associated with mortality
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