Rare Disease Report

More Classifications for Juvenile Huntington's Disease Needed

OCTOBER 08, 2018
Rachel Lutz
It might be prudent to reclassify certain types of juvenile Huntington’s disease patients, as they are not all alike—and vastly differ from adult-onset Huntington’s disease patients, according to a recent study, which was the first of its kind to examine the available worldwide juvenile Huntington’s disease patient cohort on a longitudinal basis.

Juvenile cases account for about 6% to 10% of all Huntington’s disease patients, the investigators said, and can even affect the very young.

A multinational team of investigators conducted a retrospective analysis of juvenile Huntington’s disease patients in order to characterize the disease, as well as the effects of the disease presentation, progression, and survival. The patients in the analysis were all aged 20 years or younger and had disabling psychiatric symptoms and/or motor symptoms, but not psychiatric symptoms alone. These patients were compared to Huntington’s disease patients between the ages of 30 and 60 years.

The investigators classified the juvenile patients into 2 groups: highly expanded (HE) or low expansion (LE) mutations after longitudinal analysis. Primarily, the investigators compared the CAG repeat mutation between these cohorts to arrive at their conclusions.

Between June 2004 and March 2018, the study authors identified 580 possible patients, of which 36 met their juvenile Huntington’s definition and 197 met the adult-onset definition. After reviewing caregiver reports, the investigators found that the HE subgroup often presented gait disturbance as a first symptom. Loss of hand dexterity was more common in the LE subgroup as a first symptom.

Other symptoms included developmental delay (zero vs. 9 in the LE and HE groups, respectively), severe gait impairment (9 in LE vs. 9 in HE), and seizures (3 in LE and 8 in HE). It appeared to the investigators that disease progression was more rapid in the juvenile groups compared with the adult-onset Huntington’s patients.

"Our study identifies the most aggressive juvenile-pediatric variant, that affects children, with clinical manifestations and brain damage characteristics in which a deep part of the brain, called striatum, does not seem to develop properly, starting the neurodegeneration process much later during life”, said lead author Dr. Ferdinando Squitieri in a recent statement. “Our hope, therefore, is to act on the malfunction of nerve cells, even before their death, to prevent the onset and progression of the disease.”
There were 121 deceased patients involved in the study, and investigators determined that median survival was shorter in the juvenile cohort (17 patients) compared with the adult-onset group (104 patients).

The study authors believe that their findings will pave the way for future therapies especially because current treatment options are so limited.

In a related editorial, Julie C. Stout of Monash University in Australia argued that juvenile Huntington’s disease patients “should not be left behind.”

In the study, Dr. Stout wrote, the team had a small sample size; however, that should not be overlooked because of the small number of patients with the disease compared to adult-onset cases. By dividing the pediatric patients, the investigators showed there were more nuances to juvenile Huntington’s than previously thought.

“The retrospective study of 36 children and adolescents with juvenile Huntington’s disease reported by Caterina Fusilli and colleagues in The Lancet Neurology is extraordinary because this sample size, which is large considering the low prevalence rate, provides a rich opportunity to examine key features of juvenile Huntington’s disease,” she wrote. “This study is also a reminder of how little is known about the clinical and biological manifestations of this form of Huntington’s disease.”

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