Also known as: Bilateral striatal degeneration and progressive polyneuropathy; Striatal necrosis, bilateral, and progressive polyneuropathy


1. The Disease:

Thiamine metabolism dysfunction syndrome-4 is an autosomal recessive metabolic disorder characterized by childhood onset of episodic encephalopathy, often associated with a febrile illness, and causing transient neurologic dysfunction. Most patients recover fully, but some may have mild residual weakness. Affected individuals also develop a slowly progressive axonal polyneuropathy beginning in childhood. Brain imaging during the acute episodes shows lesions consistent with bilateral striatal degeneration or necrosis.

2. The symptoms:

Acute encephalopathic episodes associated with striatal necrosis on brain imaging as well as a progressive chronic polyneuropathy. All patients had normal early psychomotor development, with onset of episodic acute encephalopathic episodes between ages 3.5 and 6.5 years old. Lack of early signs or symptoms does not exclude the diagnosis.

Episodes characterized by lethargy, muscle weakness resulting in paralysis, areflexia, and dysarthria associated with nonspecific febrile illness; followed by complete resolution and no loss of psychomotor development, although most had residual mild distal weakness.

In addition to encephalopathic episodes, all sibs had childhood onset of progressive chronic polyneuropathy characterized by motor difficulties, frequent falls, and distal weakness and atrophy of the lower limbs, accompanied by lower limb contractures and foot deformities. Electrophysiologic studies showed an axonal motor neuropathy. All sibs had age-appropriate cognition at ages 7 to 20 years.

Laboratory investigations showed mild increased lactate in the cerebrospinal fluid (CSF) during the acute phase, and brain imaging showed bilateral multiple T2-hyperintense lesions in the caudate and putamen, with sparing of the globus pallidus.

3. Actions to take in case of early diagnosis:

Biochemical correlation is recommended with lactate in CSF.

Brain MRI can show T2-hyperintense lesions basal ganglia.

THMD4 is a lifelong disease requiring lifetime management and regular follow-up with a Paediatric Neurology Center Management is provided by multidisciplinary team.

Acute episodes are prevented by high-dose thiamine treatment (600 mg/day). Mild clinical signs and basal ganglia involvement can precede the acute encephalopathic onset of the disease, potentially allowing treatment anticipation and prevention of acute brain damage.

Thiamine therapy did not improve peripheral axonal neuropathy in some patients, but who were treated early, peripheral neuropathy did not occur, suggesting a possible preventative effect.

Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings.

4. For more information:

Biblio: Porta F, Siri B, Chiesa N, et al. SLC25A19 deficiency and bilateral striatal necrosis with polyneuropathy: a new case and review of the literature. J Pediatr Endocrinol Metab. 2020;34(2):261-266. Published 2020 Nov 19. doi:10.1515/jpem-2020-0139