Sengers Syndrome

At a glance

Mitochondrial energy metabolism disorder. Characterized by congenital cataract, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis. Severe neonatal form with death in infancy and milder form (survival into fourth decade) recognized.

Synonym

Cataract-Cardiomyopathy Syndrome.

Incidence

A total of 17 affected families reported. Originally described in families originated from the southeast region of the Netherlands, now other non-Caucasian ethnicities recognized.

Genetic inheritance

Autosomal recessive.

Pathophysiology

Mutation of the Acylglycerol Kinase (AGK) gene on 7q34. The infantile form of Sengers Syndrome is caused by homozygous AGK nonsense mutations and is characterized by early onset (within the first few months of life) cardiomyopathy and lactic acidosis that causes death in infancy. Some patients who carry at least one AGK splice site variant or a start codon mutation develop a milder form of Sengers Syndrome and have a markedly better prognosis. Acylglycerol kinase catalyzes the formation of phosphatidic acid and lysophosphatidic acid that can participate in phospholipid synthesis or act as signaling molecules regulating a number of cell processes. Histologically, abnormality of mitochondria and storage of lipid and glycogen are found in both skeletal and heart muscle.

Diagnosis

Clinical features and measurement of plasmatic levels of lactate obtained at rest and after exercise. A biopsy of the skeletal and cardiac muscle confirms the diagnosis.

Clinical aspects

Patients usually present with congenital cataract and followed by hypertrophic cardiomyopathy, usually a diffuse and symmetrical type. Hypertrophic cardiomyopathy is progressive and by far the main cause of premature death. A distinct feature is the development of marked lactate acidemia on mild exercise. Other features include easy fatigue, muscular hypotonia, and delayed motor development. Significant arrhythmia may occur in later stages of disease. No treatment currently available, genetic counselling necessary. Screening for AGK mutations in infants with cataracts.

Precautions before anesthesia

An anesthesiology consultation is highly recommended before elective surgical procedure. A complete cardiac medical history must be obtained, including exercise tolerance and fatigability. Full cardiac evaluation including ECG, chest radiograph, echocardiogram for left ventricular and valvular function, Holter monitoring for arrhythmia, cardiac catheterization, and endocardial biopsy when indicated. Check plasma lactate level before, during, and after procedure if possible. Patients receiving cardiotonic medications must continue until the day of surgery. Check plasma electrolyte (eg, potassium in patients on digoxin).

Anesthetic considerations

Anesthetic technique should be tailored to the condition of the cardiac function and to the surgical procedure planned. Many of these patients are anesthetized for various ophthalmological procedures without problems. Continuous ECG monitoring is mandatory because of the potential for arrhythmia and coronary ischemia. Premedication to avoid stress and anxiety is recommended. ...