Protection From Clinical Peripheral Sensory Neuropathy in Alström Syndrome in Contrast to Early-Onset Type 2 Diabetes

Paisey, Richard; Paisey, Rosamund M.; Thomson, Mary P; Bower, L; Maffei, Pietro; Shield, Julian; Barnett, Sue; Marshall, Jan D.

doi:10.2337/dc08-1584

Cited by 19 publications

(11 citation statements)

References 13 publications

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“…In addition, he suffered from peripheral neuropathy, which has been reported to be remarkably absent in Alström patients. 12 However, the early-onset retinitis pigmentosa and complete blindness by age 17, the early-onset hearing impairment, insulin resistance, cirrhosis and liver steatosis, and splenomegaly were suggestive of Alström syndrome. In the absence of many key features of Alström syndrome, this diagnosis was not evoked prior to the genetic study.…”

Section: Discussionmentioning

confidence: 99%

A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient

et al. 2013

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Insulin-dependent juvenile-onset diabetes may occur in the context of rare syndromic presentations suggesting monogenic inheritance rather than common multifactorial autoimmune type 1 diabetes. Here, we report the case of a Lebanese patient diagnosed with juvenile-onset insulin-dependent diabetes presenting ketoacidosis, early-onset retinopathy with optic atrophy, hearing loss, diabetes insipidus, epilepsy, and normal weight and stature, who later developed insulin resistance. Despite similarities with Wolfram syndrome, we excluded the WFS1 gene as responsible for this disease. Using combined linkage and candidate gene study, we selected ALMS1, responsible for Alströ m syndrome, as a candidate gene. We identified a novel splice mutation in intron 18 located 3 bp before the intron-exon junction (IVS18-3T4G), resulting in exon 19 skipping and consequent frameshift generating a truncated protein (V3958fs3964X). The clinical presentation of the patient significantly differed from typical Alströ m syndrome by the absence of truncal obesity and short stature, and by the presence of ketoacidotic insulin-dependent diabetes, optic atrophy and diabetes insipidus. Our observation broadens the clinical spectrum of Alström syndrome and suggests that ALMS1 mutations may be considered in patients who initially present with an acute onset of insulin-dependent diabetes.

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Section: Discussionmentioning

confidence: 99%

A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient

et al. 2013

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“…In another UK study, 12 of 30 (40%) patients aged 13–35 years had evidence of neuropathy, six (20%) of whom had evidence of ulceration 52. This would suggest that neuropathy can present in younger adults with T2DM at an earlier stage (mean duration of diabetes was 1.8 years).…”

Section: Clinical Outcomesmentioning

confidence: 97%

Type 2 diabetes in younger adults: the emerging UK epidemic

Wilmot

Davies

Yates

et al. 2010

Postgraduate Medical Journal

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There is an emerging epidemic of type 2 diabetes (T2DM) in younger adults. They represent an extreme phenotype: likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black or minority ethnic origin, and come from less affluent socioeconomic groups. An accurate diagnosis of T2DM in younger adults, while essential to guide management, can be challenging even for the experienced diabetologist. Comorbidities such as hypertension, nephropathy and hyperlipidaemia are prevalent in this group, and, despite the lack of longitudinal data, they represent a very high risk group, with a need for aggressive management. This focused review of the epidemiology, aetiology, clinical outcomes, comorbidities and management of younger adults with T2DM will provide the non-specialist with up-to-date insight into the UK's emerging epidemic.

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“…This concerns the striking absence of peripheral neuropathy in Alström syndrome participants despite severe hyperglycemia and hypertriglyceridemia from adolescence compared with weight and height and age-matched persons with onset of type 2 DM in adolescence. 34 …”

Section: Discussionmentioning

confidence: 99%

Prediction of protective sensory loss, neuropathy and foot ulceration in type 2 diabetes

Paisey

Darby

George

et al. 2016

BMJ Open Diab Res Care

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ObjectivesTo prospectively determine clinical and biochemical characteristics associated with the development of peripheral neuropathy, loss of protective sensation, and foot ulceration in persons with type 2 diabetes mellitus (DM) over 7 years.Research design and methodsGraded monofilament (MF) testing, vibration perception threshold, and neuropathy symptom questionnaires were undertaken in 206 participants with type 2 DM without peripheral vascular disease or history of foot ulceration and 71 healthy participants without DM at baseline and after 7 years. 6 monthly glycosylated hemoglobin (HbA1c) levels and annual serum lipid profiles were measured during follow-up of those with DM. Incident foot ulceration was recorded at follow-up.ResultsTaller stature and higher quartiles of serum triglyceride and HbA1c levels were associated with neuropathy at follow-up (p=0.008). Remission of baseline neuropathy was observed in 7 participants at follow-up. 9 participants with type 2 DM developed foot ulcers by the end of the study, only 1 at low risk. Mean HbA1c levels were higher in those who developed foot ulceration (p<0.0001). 1 participant with neuropathy throughout developed a Charcot foot. Failure to perceive 2 or more 2, 4 and 6 g MF stimuli at baseline predicted loss of protective sensation at follow-up.ConclusionsTall stature and worse metabolic control were associated with progression to neuropathy. Mean HbA1c levels were higher in those who developed foot ulcers. Graded MF testing may enrich recruitment to clinical trials and assignation of high risk for foot ulceration.

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Protection From Clinical Peripheral Sensory Neuropathy in Alström Syndrome in Contrast to Early-Onset Type 2 Diabetes

Cited by 19 publications

References 13 publications

A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient

A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient

Type 2 diabetes in younger adults: the emerging UK epidemic

Prediction of protective sensory loss, neuropathy and foot ulceration in type 2 diabetes

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