Sengers Syndrome

Sengers syndrome is a rare autosomal recessive condition characterised by congenital cataract, hypertrophic cardiomyopathy, muscle weakness and lactic acidosis after exercise.

Signs and symptoms

There are two forms of the disease - a lethal neonatal form and a chronic form.

Hypertrophic cardiomyopathy is diagnosed at birth in half. Death in the first year is usually due to cardiac failure. Marked lactic acidemia occurs with even limited muscular exertion.

The chronic form have stable cardiomyopathy and myopathy with a normal intellect.

Other reported features include nystagmus, strabismus, hypotonia, hyporeflexia and delayed motor development.

Genetics

This disease is caused by mutations in AGK or SLC25A4 genes. The AGK gene encodes the mitochondrial acylglycerol kinase which plays a role in the assembly of adenine nucleotide translocator. The SLC25A4 gene encodes the heart and muscle specific isoform 1 of the mitochondrial adenine nucleotide translocator.

Diagnosis

The diagnosis may be provisionally made on clinical grounds. Further diagnostic tests include serum and urine analysis for lactic acid, a chest X-ray (or cardiac CT or MRI) and echocardiography. Biopsies from cardiac and skeletal muscle will show the presence of lipid and glycogen. testing for mitochondrial abnormalities, ANT deficiency and decreases of respiratory chain complexes I and IV can also be done.

Differential diagnosis

• Isolated ATP synthase deficiency
• Barth syndrome
• TMEM70 deficiency

Treatment

Surgery for the cataracts may be needed. Medical treatment for the cardiac failure will be required. Treatment is otherwise supportive.

Prognosis

About half the patients die within the first year of life. Because of its rarity the prognosis for the chronic form is not well established but survival into adulthood has been reported.

Epidemiology

Sengers syndrome is a rare disorder. About 40 cases have been reported worldwide.

History

This condition was first described in 1975.