FAHN/SPG35: a narrow phenotypic spectrum across disease classifications.

The endoplasmic reticulum enzyme fatty acid 2-hydroxylase (FA2H) plays a major role in the formation of 2-hydroxy glycosphingolipids, main components of myelin. FA2H deficiency in mice leads to severe central demyelination and axon loss. In humans it has been associated with phenotypes from the neurodegeneration with brain iron accumulation (fatty acid hydroxylase-associated neurodegeneration, FAHN), hereditary spastic paraplegia (HSP type SPG35) and leukodystrophy (leukodystrophy with spasticity and dystonia) spectrum. We performed an in-depth clinical and retrospective neurophysiological and imaging study in a cohort of 19 cases with biallelic FA2H mutations. FAHN/SPG35 manifests with early childhood onset predominantly lower limb spastic tetraparesis and truncal instability, dysarthria, dysphagia, cerebellar ataxia, and cognitive deficits, often accompanied by exotropia and movement disorders. The disease is rapidly progressive with loss of ambulation after a median of 7 years after disease onset and demonstrates little interindividual variability. The hair of FAHN/SPG35 patients shows a bristle-like appearance; scanning electron microscopy of patient hair shafts reveals deformities (longitudinal grooves) as well as plaque-like adhesions to the hair, likely caused by an abnormal sebum composition also described in a mouse model of FA2H deficiency. Characteristic imaging features of FAHN/SPG35 can be summarized by the 'WHAT' acronym: white matter changes, hypointensity of the globus pallidus, ponto-cerebellar atrophy, and thin corpus callosum. At least three of four imaging features are present in 85% of FA2H mutation carriers. Here, we report the first systematic, large cohort study in FAHN/SPG35 and determine the phenotypic spectrum, define the disease course and identify clinical and imaging biomarkers.

Factors associated with prevalence and severity of caries experience in preschool children.

OBJECTIVES: The aim of the present study was to examine the prevalence and severity of caries experience in the primary dentition of preschool children and to assess the association of disease distribution with oral hygiene levels, reported oral health behaviours and socio-demographic factors. METHODS: Study samples comprised 1250 3-year-old and 1283 5-year-old pre-school children from four distinct geographical areas in Flanders. Information on oral hygiene and dietary habits, oral health behaviours and socio-demographic variables was collected using questionnaires completed by the parents. Clinical examinations were performed using standardized criteria. Caries experience was recorded at the level of cavitation (d(3) level). Simple as well as multivariable logistic regression analyses were performed in order to identify factors associated with prevalence and severity of caries experience. RESULTS: Visible plaque was present in 31% of 3-year-olds and 37% of 5-year-olds. In 3-year-olds, 7% presented with caries experience while this was the case in 31% of 5-year-olds. Multivariable logistic regression revealed significant associations, in 3-year-olds, of caries experience with presence of dental plaque (OR = 7.93; 95% CI: 2.56-24.55) and reported consumption of sugared drinks at night (OR = 7.96; 95% CI: 1.57-40.51). In 5-year-olds, significant associations were seen with age (OR = 7.79; 95% CI: 2.38-25.43), gender (OR = 0.37 with 95% CI: 0.19-0.71 for girls), presence of visible dental plaque (OR = 3.36; 95% CI: 1.64-6.89) and reported habit of having sugar-containing drinks in between meals (OR = 2.60 with 95% CI: 1.16-5.84 and OR = 3.18 with 95% CI: 1.39-7.28, respectively for 1x/day and > 1x/day versus not every day). In 5-year-olds with caries experience (30.8% of total sample), the severity of disease was further analysed (d(3)mft between 1 and 4 versus d(3)mft 5 or higher). Multivariable analyses showed a significant association with gender [girls more likely to have higher disease levels; OR = 4.67 (95% CI: 1.65-13.21)] and with presence of plaque (OR = 3.91 with 95% CI: 1.23-12.42). CONCLUSIONS: Presence of visible plaque accumulation and reported consumption of sugared drinks were associated with prevalence of caries experience in Flemish preschool children. Severity of disease was associated with gender and with presence of plaque. Results underline the importance of plaque control and diet management from very young age on.