Alpers syndrome

Alpers syndrome, also known as Alpers-Huttenlocher syndrome or progressive cerebral poliodystrophy, is a rare childhood neurodegenerative POLG-related disorder. Along with Leigh syndrome, it is one of the commonest childhood mitochondrial disorders ¹. 

Epidemiology

Alpers syndrome is incredibly rare. The estimated prevalence is 1 per 100,000. 

Clinical presentation

Alpers syndrome generally affects infants within the first year of life, but cases have been reported later in childhood through to early adulthood ^2-4. Affected individuals often present with severe, refractory status epilepticus ². Loss of motor coordination, decreased muscle tone, cognitive decline, optic nerve atrophy, and hepatic impairment are often reported in disease progression ^1,5. 

Pathology

Genetics

Autosomal recessive mutations in the DNA Polymerase Gamma, Catalytic Subunit (POLG) gene have been implicated in the majority of cases ⁵. 

Radiographic features

Neuroimaging findings are most frequently described.

CT

Findings are often subtle and include low densities in the cortex and white matter, especially in the occipital lobes, and cerebral atrophy ⁷.

MRI

Features described include:

• regions of increased signal intensity on T2-weighted sequences and DWIwith associated diffusion restriction, most often in the occipital lobes and thalami, involving both the cortex and deep gray matter ^7-9

  • these regions often correspond to areas of pathological electroencephalogram (EEG) activity and may even be absent if no recent seizure activity has occurred ^7-9

• generalised cerebral atrophy, although may have an occipital preponderance ^7-9

• prior to development of POLG-related neurological manifestations, features of chronic hepatic encephalopathy, such as increased signal intensity on T1-weighted sequences in the globi pallidi and subthalamic regions, or acute hepatic encephalopathy may be seen ¹⁰

• these features may be detected in prenatal MRI ⁸

MR spectroscopy may demonstrate an elevated lactate signal intensitypeak and a reduced NAA signal intensity-creatine ratio, in areas of high diffusion signal restriction¹⁰.

Treatment and prognosis

Treatment focuses on symptoms control. Sodium valproate as an agent for epilepsy control is generally avoided due to its hepatotoxicity which may result in rapid decline in liver function in patients with a predisposition to liver failure, such as those with Alpers syndrome ⁶.

Alpers syndrome often progresses rapidly, leading to death in childhood ⁵. 

History and etymology

Alpers syndrome was first described by Bernard Alpers in 1931 ¹¹. In the late 1970s, Peter Huttenlocher associated further patient phenotypes with that of Alpers' patient and the eponymous name was coined ¹².

See also

• POLG-related disorders