[MIM 203 700]

( Progressive infantile Poliodystrophy, Alpers-Huttenlocher syndrome)

Very rare: incidence estimated at 1/100,000 to 1/250,000 births. Autosomal recessive Transmission. Mitochondrial cytopathy due in 90 % of cases to a mutation of POLG gene (15q25)  coding for the mitochondrial DNA polymerase, leading to mitochondrial DNA depletion and reduced activity of the complexes I, III and IV of the respiratory chain within the affected mitochondria. 

Association to varying degrees of: psychomotor regression, epilepsy, liver disease.

The first symptoms appear during the two first years of life in 80 % of cases (extremes: from 3 months to 8 years of age), but the onset is later (between 17 and 24 years of age) in 20 % of the cases. 

Development is initially normal. The onset and the severity of signs and symptoms is highly variable. 

Clinical presentation:

-         hypoglycemia during fasting

-         encephalopathy complicating usual viral infections

-         difficult to control epilepsy, sometimes status epilepticus

-         psychomotor regression in steps (often post-infectious)

-         fulminant hepatitis; sometimes chronic liver disease with microvesicular steatosis and bile duct proliferation and evolution to cirrhosis.

-        cortical blindness appears in 25 % of cases. 

-        gastrointestinal motility disorders and cardiomyopathy (10 %) may appear. 

:MRI: reduced brain volume, asymmetrical cortical, thalamic and basal ganglia damage. 

Prognosis is bad; death is generally rapid after the diagnosis.

Precautions: avoid valproic acid to treat epilepsy because there is a risk of acute liver failure; contraindication to liver transplantation.

Despite liver failure, cases of vascular thrombosis following the insertion of a central venous catheter have been described (probably due to a  deficiency in factor C or S, or antithrombin).

Anesthetic implications: 

echocardiography; check liver function; management of a mitochondrial cytopathy (see this topic)

References : 

-         Saneto RP, Cohen BH, Copeland WC, Naviaux RK. 
Alpers-Huttenlocher syndrome. 
Pediatr Neurology 2013; 48: 167-78.

-         Lee WS, Sokol RJ. 
Mitochondrial hepatopathies : advances in genetics, therapeutic approaches and outcomes. 
J Pediatr 2013 ; 163 :  942-8.

Updated: December 2019