Incidence and carrier frequency of Sandhoff disease in Saskatchewan determined using a novel substrate with detection by tandem mass spectrometry and molecular genetic analysis.

Sandhoff disease is a rare progressive neurodegenerative genetic disorder with a high incidence among certain isolated communities and ethnic groups around the world. Previous reports have shown a high occurrence of Sandhoff disease in northern Saskatchewan. Newborn screening cards from northern Saskatchewan were retrospectively screened in order to investigate the incidence and determine the carrier frequency of Sandhoff disease in these communities.

A polymerase chain reaction-based genotyping assay for detecting a novel Sandhoff disease-causing mutation.

Sandhoff disease is a rare genetic disorder, however, some northern Saskatchewan communities have a high incidence of the disease (for which the causative mutation has not been described). We discovered a novel mutation causing Sandhoff disease in this community and validated a molecular assay to detect the mutant allele. DNA sequencing was used to search for mutations in the HEXB gene from the most recently affected patient.

Elevated neonatal 3-OH isovalerylcarnitine due to breast milk sources in maternal 3-MCC deficiency.

We report a positive newborn screen for 3-hydroxyisovalerylcarnitine (C(5)OH) with an absence of 3-methylcrotonyl-coenzyme A carboxylase deficiency in the neonate. Subsequent blood tests demonstrated persistently elevated C(5)OH. Serial testing of the mother identified markedly elevated C(5)OH in both maternal blood and breast milk.