Very rare progressive neurologic disorder,
predominantly involving the gray matter, and characterized by spasticity and
myoclonia. Dementia ensues combined
with hepatic cirrhosis. Poor prognosis, generally within a few months.
Possible exacerbation by stress or infection.
Progressive Sclerosing Poliodystrophy; Alpers
Huttenlocher Syndrome; Alpers Diffuse Degeneration of Cerebral Gray Matter
with Hepatic Cirrhosis; Alpers Progressive Infantile Poliodystrophy;
Christensen Disease; Christensen-Krabbe Disease; Diffuse Cerebral
Degeneration in Infancy; Progressive Cerebral Poliodystrophy; Progressive
Neuronal Degeneration of Childhood with Hepatic Cirrhosis.
First recognized by Alfons Maria Jakob and first described
by Bernard Alpers in 1931.
Fewer than 50 cases have been described. Both genders
are equally affected.
Autosomal recessive. Certain affected
individuals may inherit the genetic predisposition for the disorder.
However, some researchers do not believe in a genetic cause, and increasing
evidence indicates that Alpers syndrome may be a manifestation of childhood prion
Acute impairment of mitochondrial function leading
to a potentially reversible cytotoxic cerebral edema could play an important
pathogenetic mechanism in Alpers syndrome. Mitochondrial mutations or
deletions may cause a defect in the electron transport chain and
consequently impaired oxidative phosphorylation, oxidative stress, and
Onset is early in life, with convulsions (most often in
the second year of life). The diagnosis of Alpers syndrome usually follows a
thorough clinical examination followed by special investigations. Abnormal
electroencephalography (high-amplitude slow waves in combination with
lower-amplitude polyspikes), progressive brain atrophy on CT or MRI,
microcephaly, loss of visual evoked potentials, and abnormal liver function
tests point to the diagnosis of Alpers syndrome. Histopathologic examination
of the brain reveals spongiform degeneration and microcystic lesions with
loss of neurons and demyelination, reactive cortical gliosis, and
accumulation of lipids. Severe loss of almost all granular cells and
persistent Purkinje cells can be found in the cerebellar cortex. The
cerebral lesions can be unilateral or bilateral and predominately affect the
occipital and parietal cortex, but cerebellum, brainstem, and basal ganglia
also are involved. Widespread necrosis may involve the hippocampus,
thalamus, substantia nigra, and amygdala.
Alpers disease usually begins in early childhood,
predominantly affects the cerebral gray matter, and is characterized by
progressive dementia and/or regression (loss of milestones), growth
retardation, audiovisual impairment (blindness is possible), intractable
seizures, myoclonus, ataxia, spasticity, areflexia, nystagmus, hypotonia,
partial paralysis, dysphagia, and often liver damage. Liver involvement
usually is a late sign and may result in jaundice, liver failure, and
hepatic cirrhosis. Liver transplant does not result in clinical improvement
and is not recommended at this point. Clinical exacerbation of seizures
during stress (surgery) or infections has been described. Several
biochemical abnormalities have been described in patients with Alpers
disease, including dysfunction of the citric acid cycle, decreased levels of
cytochromes a and aa3, decreased utilization of pyruvate, and deficiency of
pyruvate dehydrogenase. As the disease progresses, many children become
hypotonic, anemic, and thrombocytopenic. Progressive psychomotor
deterioration (commonly with status epilepticus) in combination with acute
hepatic failure finally ...