The Hunter's Hope Krabbe Family Database

Newborn screening for Krabbe disease in New York State: the first eight years’ experience

“…It is fairly well accepted that an individual homozygous for the 30-kb deletion will develop EIKD, and an individual carrying p.G270D in conjunction with any other mutation will develop later-onset KD. 2 Others have found little association between GALC activity and disease onset or severity, 1 and there is still limited knowledge of the effects of specific mutations on GALC activity. It is unclear whether novel variants detected in our population represent pathogenic mutations or are rare variants that slightly modify GALC activity in a manner similar to other more common polymorphisms such as p.I546T and p.R168C but are not sufficient to cause disease.…”

Krabbe disease: the importance of early diagnosis for prognosis

“…DK is rare, with an incidence of 1/100,000 liveborns (4) . It presents as a hereditary recessive autosomal disorder, with a deficiency of GALC due to the mutation of the GALC gene located in chromosome 14q31 -there are also more than 60 known mutations in this gene (5) .…”

“…In the infantile form, the main symptoms are excessive crying, irritability, stiffness, seizures, and difficulty holding up the head. In the late onset form there are alterations in gait, motor development delay, stiffness, loss of vision, dysphagia, and seizures (4) .…”

Should states adopt newborn screening for early infantile Krabbe disease?

“…The natural history is well described for clinically identified individuals with Krabbe disease (Hunters Hope registry data). 3,4 The original evidence review in 2009 concluded that there is poor genotype-phenotype correlation 5 other than homozygosity of the 30-kb deletion, which is strongly predictive of EIKD. Low levels of galactocerebrosidase activity 4,6 do not entirely predict the age of symptom onset or severity of white matter changes.…”

“…3,4 The original evidence review in 2009 concluded that there is poor genotype-phenotype correlation 5 other than homozygosity of the 30-kb deletion, which is strongly predictive of EIKD. Low levels of galactocerebrosidase activity 4,6 do not entirely predict the age of symptom onset or severity of white matter changes. Subsequent conclusions from the registry suggest "The later onset Krabbe phenotypes differ from those with early infantile disease, but no specific predictor of phenotype was identified. "…”