Acute metabolic decompensation and sudden death in Barth syndrome: report of a family and a literature review

Abstract

Barth syndrome presents in infancy with hypotonia, dilated cardiomyopathy, and neutropenia. We report a patient whose family history included two males who had died suddenly at the age of 15 days and 2 years, respectively. The index case presented with acute metabolic decompensation at 13 days of age. Within 8 h of presenting with metabolic acidosis (pH 7.13), lactic acidemia (18.5 mmol/l), hyperammonemia (375 microg/dl), hypoglycemia (25 mg/dl), and coagulopathy, the patient developed respiratory failure and required intubation. The diagnosis was established by the presence of left ventricular noncompaction and molecular analysis (c.C153G or Y51X mutation of the TAZ gene). The gene product, taffazin, is a homologue of the glycerolipid transferases involved in the phospholipid metabolism as tetralinoleoyl-cardiolipin, a component of the mitochondrial inner membrane. In conclusion, mutations in taffazin impair mitochondrial respiratory chain complexes, which may results in the acute metabolic decompensation and sudden death; cardiac transplantation is the only possibility at the present time.

Tissue-specific splicing of an Ndufs6 gene-trap insertion generates a mitochondrial complex I deficiency-specific cardiomyopathy

“…Thus, Ndufs6 gt/gt mice are anticipated to be vulnerable to energy deficits and myocardial injury during conditions of high work stress or ischemia reperfusion. This is consistent with the observation that patients with mitochondrial cardiomyopathy often have prolonged periods of clinical stability but are susceptible to acute metabolic decompensation precipitated by fasting, infection, or other stresses (28,29). This metabolic fragility is also seen in OXPHOS disorders affecting other tissues.…”

Clinical manifestations and outcomes of pediatric chronic neutropenia

“…Only four out of 11 patients with an active disease at transplantation survived (survival rate was about 36%). 29 Cardiac transplantation can cure cardiomyopathy of patients with Barth syndrome, 19 and liver transplantation can cure the enzymatic defect of patients with glycogen storage disease type 1b.…”

“…In all these patients, BMA findings demonstrated typical hypocellular marrow with maturation arrest at the promyelocyte level (Table 1). Another four patients (three males and one female) had congenital neutropenia associated with syndromes, such as CHS, X-linked HIGM with a CD40 ligand gene mutation, glycogen storage disease type Ib with a glucose-6-phosphatetransporter (G6PT) gene mutation, and Barth syndrome with a G4.5/TAZ gene mutation 19 (Table 1). The patient with CHS diagnosed using clinical manifestations and laboratory findings was in the accelerated phase before receiving partial matched unrelated donor UCBT (HLA compatibility: 5/6 match) and died shortly after transplantation due to graft failure and severe infection.…”

Differing clinical courses and outcomes in two siblings with Barth syndrome and left ventricular noncompaction

“…LVNC patients exhibit varying degrees of deterioration in cardiac function that result in congestive heart failure, arrhythmias, thromboembolic events, and sudden cardiac death. Cardiomyopathy or LVNC most severely affects the prognosis in Barth syndrome, and cardiac decompensation may become difficult to treat, necessitating cardiac transplantation [2,6,25].…”