TAZ encodes tafazzin, a transacylase essential for cardiolipin formation and central to the etiology of Barth syndrome.

Tafazzin, which is encoded by the TAZ gene, catalyzes transacylation to form mature cardiolipin and shows preference for the transfer of a linoleic acid (LA) group from phosphatidylcholine (PC) to monolysocardiolipin (MLCL) with influence from mitochondrial membrane curvature. The protein contains domains and motifs involved in targeting, anchoring, and an active site for transacylase activity. Tafazzin activity affects many aspects of mitochondrial structure and function, including that of the electron transport chain, fission-fusion, as well as apoptotic signaling. TAZ mutations are implicated in Barth syndrome, an underdiagnosed and devastating disease that primarily affects male pediatric patients with a broad spectrum of disease pathologies that impact the cardiovascular, neuromuscular, metabolic, and hematologic systems.

Cardiolipin metabolism and its causal role in the etiology of the inherited cardiomyopathy Barth syndrome.

Cardiolipin (CL) is a phospholipid with many unique characteristics. CL is synthesized in the mitochondria and resides almost exclusively within the mitochondrial inner membrane. Unlike most phospholipids that have two fatty acyl chains, CL possesses four fatty acyl chains resulting in unique biophysical characteristics that impact several biological processes including membrane fission and fusion. In addition, several proteins directly bind CL including proteins within the electron transport chain, the ADP/ATP carrier, and proteins that mediate mitophagy. Tafazzin is an enzyme that remodels saturated fatty acyl chains within CL to unsaturated fatty acyl chains, loss of function mutations in the TAZ gene encoding tafazzin are causal for the inherited cardiomyopathy Barth syndrome. Cells from Barth syndrome patients as well as several models of Barth have reduced mitochondrial functions including impaired electron transport chain function and increased reactive oxygen species (ROS) production. Mitochondria in cells from Barth syndrome patients, as well as several model organism mimics of Barth syndrome, are large and lack cristae consistent with the recently described role of CL participating in the generation of mitochondrial membrane contact sites. Cells with an inactive TAZ gene have also been shown to have a decreased capacity to undergo mitophagy when faced with stresses such as increased ROS or decreased mitochondrial quality control. This review describes CL metabolism and how defects in CL metabolism cause Barth syndrome, the etiology of Barth syndrome, and known modifiers of Barth syndrome phenotypes some of which could be explored for their amelioration of Barth syndrome in higher organisms.

Left ventricular noncompaction (LVNC) and low mitochondrial membrane potential are specific for Barth syndrome.

Barth syndrome (BTHS) is an X-linked mitochondrial defect characterised by dilated cardiomyopathy, neutropaenia and 3-methylglutaconic aciduria (3-MGCA). We report on two affected brothers with c.646G > A (p.G216R) TAZ gene mutations. The pathogenicity of the mutation, as indicated by the structure-based functional analyses, was further confirmed by abnormal monolysocardiolipin/cardiolipin ratio in dry blood spots of the patients as well as the occurrence of this mutation in another reported BTHS proband. In both brothers, 2D-echocardiography revealed some features of left ventricular noncompaction (LVNC) despite marked differences in the course of the disease; the eldest child presented with isolated cardiomyopathy from late infancy, whereas the youngest showed severe lactic acidosis without 3-MGCA during the neonatal period. An examination of the patients' fibroblast cultures revealed that extremely low mitochondrial membrane potentials (mtΔΨ about 50 % of the control value) dominated other unspecific mitochondrial changes detected (respiratory chain dysfunction, abnormal ROS production and depressed antioxidant defense). 1) Our studies confirm generalised mitochondrial dysfunction in the skeletal muscle and the fibroblasts of BTHS patients, especially a severe impairment in the mtΔΨ and the inhibition of complex V activity. It can be hypothesised that impaired mtΔΨ and mitochondrial ATP synthase activity may contribute to episodes of cardiac arrhythmia that occurred unexpectedly in BTHS patients. 2) Severe lactic acidosis without 3-methylglutaconic aciduria in male neonates as well as an asymptomatic mild left ventricular noncompaction may characterise the ranges of natural history of Barth syndrome.

Síndrome de Bart: reporte de caso / Bart's syndrome: a case report / Síndrome de bart: reporte de caso

El Síndrome de Bart es un trastorno congénito poco frecuente, caracterizado por la asociación de epidermolisis ampollosa, ausencia congénita localizada de piel y anormalidades ungueales. En éste artículo se reporta el caso de un neonato masculino remitido al Hospital Militar Central de Bogotá, para valoración de lesiones cutáneas extensas presentes desde el nacimiento, a quien se le diagnosticó Síndrome de Bart y quien después del tratamiento mostró mejoría, con una evolución acorde a la registrada en la literatura, en la que con el tiempo se va observando una gradual resolución...

Bart's Syndrome is a rare congenital disorder, characterized by the association of bullous epidermolysis, congenital absence of areas of skin and ungueal abnormalities. This is the report of a newborn male referred to the Hospital Militar Central in Bogotá, for evaluation of extensive cutaneous lesions present a birth, who was diagnoses with Bart's syndrome and who improved with treatment, showing a gradual resolution with time, in agreement with what is seen in the literature...

A Síndrome de Bart é um transtorno congênito pouco freqüente, caracterizado pela associação de epidermolisis bolhosa, ausência congênita localizada de pele e anormalidades ungueais. Neste artigo se reporta o caso de um neonato masculino remetido ao Hospital Militar Central de Bogotá, para valoração de lesões cutâneas extensas presentes desde o nascimento, a quem se lhe diagnosticou Síndrome de Bart e quem depois do tratamento mostraram melhoria, com uma evolução conforme à registrada na literatura, na que com o tempo se vai observando uma gradual resolução...