Wolfram syndrome: Important implications for pediatricians and pediatric endocrinologists
Department of Pediatrics, Amrita Institute of Medical Sciences, Cochin, Kerala, India. Pediatric Diabetes
(Impact Factor: 2.57).
12/2009; 11(1):28-37. DOI: 10.1111/j.1399-5448.2009.00518.x
Kumar S. Wolfram syndrome: important implications for pediatricians and pediatric endocrinologists.
Available from: Sanna Häkli
- "Some case series have suggested a higher prevalence of diabetes mellitus and psychiatric disorders among relatives of patients with WS (Kumar, 2010). Furthermore, increased risk of HI has been reported in heterozygous carriers in WS families (Ohata et al, 1998). "
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ABSTRACT: Abstract Objective: Mutations in the WFS1 gene can cause Wolfram syndrome or nonsyndromic hearing impairment (HI). The objective of this study was to ascertain the presence of mutations in WFS1 among children with HI from unknown causes. Design: We screened 105 Finnish children with HI for mutations in exon 8 in WFS1. Study sample: Children were born in a defined area in Northern Finland and they had sensorineural, mild to profound, syndromic, or nonsyndromic HI. They were negative for GJB2 mutations and for the m.1555A> G and m.3243A> G mutations in mitochondrial DNA. Results: We found three rare variants and the novel p.Gly831Ser variant in WFS1. Segregation analysis suggested that the novel variant had arisen de novo. The p.Gly831Ser variant may be a new member to the group of heterozygous WFS1 mutations that lead to HI, while the pathogenicity of the rare variant p.Gly674Arg remained unclear. The other two rare variants, p.Glu385Lys and p.Glu776Val, did not segregate with HI in the families. Conclusions: WFS1 gene mutations are a rare cause of HI among Finnish children with HI.
Available from: Ryan P Duncan
- "Specifically, in young people, visual impairment correlates with spatiotemporal gait deficits [23,33]. In WFS, visual deficits are well described (for review see ) thus we expected gait impairments in individuals with WFS to correlate with measures of visual impairment. However, we did not find any correlation between visual acuity and any spatiotemporal measures of gait function, suggesting that vision may not be a key factor in the gait differences noted in WFS compared to TD individuals. "
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Classically characterized by early onset insulin-dependent diabetes mellitus, optic atrophy, deafness, diabetes insipidus, and neurological abnormalities, Wolfram syndrome (WFS) is also associated with atypical brainstem and cerebellar findings in the first decade of life. As such, we hypothesized that gait differences between individuals with WFS and typically developing (TD) individuals may be detectable across the course of the disease.
Gait was assessed for 13 individuals with WFS (min 6.4 yrs, max 25.8 yrs) and 29 age-matched, typically developing individuals (min 5.6 yrs, max 28.5 yrs) using a GAITRite ® walkway system. Velocity, cadence, step length, base of support and double support time were compared between groups.
Across all tasks, individuals with WFS walked slower (p = 0.03), took shorter (p ≤ 0.001) and wider (p ≤ 0.001) steps and spent a greater proportion of the gait cycle in double support (p = 0.03) compared to TD individuals. Cadence did not differ between groups (p = 0.62). Across all tasks, age was significantly correlated with cadence and double support time in the TD group but only double support time was correlated with age in the WFS group and only during preferred pace forward (rs= 0.564, p = 0.045) and dual task forward walking (rs= 0.720, p = 0.006) tasks. Individuals with WFS also had a greater number of missteps during tandem walking (p ≤ 0.001). Within the WFS group, spatiotemporal measures of gait did not correlate with measures of visual acuity. Balance measures negatively correlated with normalized gait velocity during fast forward walking (rs = −0.59, p = 0.03) and percent of gait cycle in double support during backward walking (rs = −0.64, p = 0.03).
Quantifiable gait impairments can be detected in individuals with WFS earlier than previous clinical observations suggested. These impairments are not fully accounted for by the visual or balance deficits associated with WFS, and may be a reflection of early cerebellar and/or brainstem abnormalities. Effective patient-centered treatment paradigms could benefit from a more complete understanding of the progression of motor and other neurological symptom presentation in individuals with WFS.
Available from: Joo-Hark Yi
- "The coexistence of DI and DM in the same patient has been rarely reported in Wolfram syndrome (known as DIDMOAD) as a congenital genetic disorder in pediatric age group, which has the concurrent association of central diabetes insipidus (CDI) with type 1 DM accompanied by optic atrophy, deafness, and infantilism2). The coexistence of CDI and type 2 DM has been noted in less than 10 adult patients, most of whom had 2 to 15 years history of type 2 DM before developing CDI3-6). "
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ABSTRACT: We report a rare case of the concurrent manifestation of central diabetes insipidus (CDI) and type 2 diabetes mellitus (DM). A 56 year-old man was diagnosed as a type 2 DM on the basis of hyperglycemia with polyuria and polydipsia at a local clinic two months ago and started an oral hypoglycemic medication, but resulted in no symptomatic improvement at all. Upon admission to the university hospital, the patient's initial fasting blood sugar level was 140 mg/dL, and he showed polydipsic and polyuric conditions more than 8 L urine/day. Despite the hyperglycemia controlled with metformin and diet, his symptoms persisted. Further investigations including water deprivation test confirmed the coexisting CDI of unknown origin, and the patient's symptoms including an intense thirst were markedly improved by desmopressin nasal spray (10 µg/day). The possibility of a common origin of CDI and type 2 DM is raised in a review of the few relevant adult cases in the literature.
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