Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report on one case of Wolfram syndrome, a rare condition, which is characterized by juvenile onset diabetes mellitus, diabetes insipidus, optic atrophy and sensorineural deafness. The findings of this 13-year follow-up show that this patient developed typical neurological complications of long-standing diabetes mellitus as in the common type 1 variant. Moreover, some peculiar signs occurred such as anosmia, ophthalmoplegia interna, and central nystagmus. Since Wolfram syndrome is probably part of a more generalized neurodegenerative disorder, long-term prognosis will depend both upon the severity of chronic diabetic complications and upon the rapidity, by which degeneration of cerebellar, pontine and brain stem structures appear. Prognosis of the cardinal clinical signs is such that optic atrophy, though usually quite rapid in the beginning, generally does not lead to complete blindness. Sensorineural hearing loss progresses very slowly so that deafness might be expected exceptionally only. The hearing deficit in classical diabetics, however, is of retrocochlear origin. Therefore, in Wolfram syndrome, a combined inner-ear and retrocochlear hearing loss may occur.
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PMID:Juvenile onset diabetes mellitus, central diabetes insipidus and optic atrophy (Wolfram syndrome)--neurological findings and prognostic implications. 185 94

Among 18 NIH probands with anosmia and hypogonadotropic hypogonadism (AHH), seven had affected relatives and three had consanguineous parents. Both sexes were equally affected and parents were phenotypically normal. Parental age was not increased. Cleft lip and palate occurred in both eugonadal and hypogonadal persons, a previously reported association that may represent variable expression of AHH. Diabetes mellitus, usually insulin-dependent, was frequent in probands and their families. Other common traits included obesity, cryptorchidism, and hearing loss. All probands were chromosomally normal. The frequency of some dermatoglyphic traits of probands differed from normal, but no trait was unique to AHH. Segregation analysis of our proband sibships was consistent with a hypothesis of autosomal-recessive inheritance with variable expression. However, genetic heterogeneity was apparent when previous reports of familial AHH were surveyed. An X-linked or male sex-limited autosomal-dominant form with unilateral renal agenesis, mental retardation, and hypotelorism has been observed. The infrequent reports of direct male-to-male transmission limit characterization of an autosomal-dominant form of AHH. Our phenotypic analysis suggests that the traits of mental retardation, renal anomalies, hypotelorism, diabetes, and hearing loss may help to distinguish various forms of AHH, whereas cryptorchidism, clefts, and obesity appear in several types of families. At present, genetic counseling is dependent upon establishing inheritance pattern after examination for the known associated anomalies.
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PMID:The syndrome of anosmia with hypogonadotropic hypogonadism: a genetic study of 18 new families and a review. 688 Dec 9

Wolfram syndrome was originally described as a combination of familial juvenile-onset diabetes mellitus and optic atrophy. Other neurological features subsequently emerged, and "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) became a commonly accepted acronym. Here, we describe 4 further cases from 2 families, in whom there occurred previously unrecognized neurological features, central apnea and neurogenic upper airway collapse, together precipitating primary respiratory failure (fatal in 1 case), startle myoclonus (in 2 unrelated cases), axial rigidity, and Parinaud's syndrome. Magnetic resonance images revealed striking brainstem atrophy affecting, in particular, the pons and midbrain. The mitochondrial DNA from 3 cases (and relatives) showed no evidence of any of the previously reported abnormalities. These neurological and neuroradiological features, in conjunction with (1) analyses showing the neurodegenerative origin of optic atrophy, deafness, diabetes insipidus, and incontinence, (2) other previously reported neurological complications (including anosmia, ataxia, epilepsy, and neuropsychiatric and cognitive abnormalities), and (3) the very small number of published postmortem studies, indicate that Wolfram syndrome should be reemphasized as a unique hereditary neurodegenerative disorder with prominent optic atrophy and diabetes mellitus.
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PMID:Wolfram syndrome: hereditary diabetes mellitus with brainstem and optic atrophy. 860 54

Poor nutritional status in patients with cystic fibrosis (CF) is associated with increased mortality. Patients with CF often have a decreased sensation of smell secondary to recurrent sinus infections or sinus surgery; in other CF populations, a decreased sensation of smell has been associated with poor nutritional status. We hypothesized that a decreased sensation of smell would be associated with worse nutritional status in patients with CF. We studied 50 (26 F and 24 M) of 58 consecutive patients with CF (86%) aged 14-53 years (28 +/- 8; mean +/- SD) who attended the University of Washington Medical Center from June 1994 to March 1995 and who agreed to participate. Demographic information was obtained, and nutritional status was assessed by ideal body weight, arm muscle area, arm fat area, pancreatic sufficiency, insulin-requiring diabetes, vitamins A and E levels, albumin, iron, iron binding capacity, ferritin, cholesterol, and zinc levels. Objective sensation of small was examined (Sensonics, Philadelphia, PA), a sinus compacted tomogram (CT) was performed, and a questionnaire for prior sinus symptoms, sinus surgery, medications, and subjective sensation of smell was administered. Twenty-seven of 49 subjects (55%) had an objective decrease in sensation of smell, 23/50 (46%) had had prior sinus surgery. 46/50 (92%) were pancreatic insufficient, and 8/50 (16%) were insulin-requiring diabetics. Weight for height ranged from the 38th to 157th percentile (100 +/- 18; mean +/- SD). Arm muscle area ranged from the < 5th to the 75th percentile (25 +/- 23; mean +/- SD). Arm fat area ranged from the < 5th to the 95th percentile (45 +/- 39; mean +/- SD). Sinus CT scans were abnormal in all patients (100%). Patients with anosmia were more likely to have had sinus surgery, but their nutritional status was no different from that of patients with a normal sensation of smell. We conclude that decreased sensation of smell is common in patients with CF, especially those with prior sinus surgery. Subjective sensation of smell and sinus CT scans were unreliable indicators of a decreased objective sensation of smell. In this pilot study, no association was found between sensation of smell and nutritional status.
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PMID:Sensation of smell does not determine nutritional status in patients with cystic fibrosis. 926 54

We report a patient with chronic active hepatitis C developing acute anosmia during interferon (IFN) therapy. On July 31, he began receiving 6 MU of IFN-alpha daily. On September 26, he failed to smell gas leaking from a gas cooker, so IFN therapy was discontinued. He showed no reaction on a standard olfactory acuity test. As the patient had borderline diabetes, the association of anosmia with impaired glucose tolerance cannot completely be excluded, but his anosmia was probably induced by IFN therapy, since anosmia developed 10 days after the initiation of the IFN therapy, without any deterioration of his glucose intolerance.
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PMID:Interferon-induced anosmia in a patient with chronic hepatitis C. 944 93

Kallmann's syndrome is characterized by hypogonadotropic hypogonadism and anosmia. Assisted reproductive techniques such as intracytoplasmic sperm injection (ICSI) may be required to treat the infertile couple with oligozoospermia. Rare complications have been described in patients with Kallmann's syndrome, but gestational diabetes has not previously been reported. A case of Kallmann's syndrome with infertility is reported. Ovulation was successfully induced by human menopausal gonadotropin therapy, but pregnancy could not be achieved by artificial insemination or by conventional in vitro fertilization, although the husband had only moderate oligozoospermia. A high fertilization rate of the retrieved oocytes and successful pregnancy was achieved by ICSI. The pregnancy was complicated by gestational diabetes that was managed by insulin therapy. Successful ovulation induction in Kallmann's syndrome is not rare, but ICSI may be needed in selected cases. Some recent data have suggested that diabetes may occur in patients with Kallmann's syndrome, but further investigation is needed to establish whether gestational diabetes is associated with Kallmann's syndrome or is purely coincidental.
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PMID:Kallmann's syndrome: pregnancy through intracytoplasmic sperm injection and complicated by gestational diabetes. 1172 53

A 19-year-old man was admitted to our hospital for delayed puberty. At birth, he had macrocephalia and showed delayed physical and mental development. At 9 years of age, right cryptorchism was diagnosed. His parents had noticed that he could not recognize any smells since his infancy. Physical examination on admission revealed ocular hypertelorism, high myopia, high arched palate, and intermittent external strabismus. Sense of smell was scaled out by olfactometry. External genitalia were infantile. Neurological examination showed on IQ of 83, and mild truncal ataxia. Magnetic resonance imaging (MRI) showed a cystic distension of the IV ventricle, partial aplasia of the cerebellar vermis, elevation of the tentorium cerebelli, enlargement of the III ventricle, and agenesis of the corpus callosum. These findings revealed that the patient had Dandy-Walker malformation. The basal FSH, LH, and testosterone levels were all low compared with normal adult reference values. The serial LH-RH provocation tests showed stepwise LH and FSH elevation. After the fifth day of LH-RH administration, both LH and FSH responses clearly improved. Olfactory tracts were defective in MRI findings. These findings were consistent with hypogonadotropic hypogonadism of hypothalamic origin with anosmia, and the patient was therefore diagnosed with Kallmann syndrome. Sequence analysis of the KAL1 gene showed no mutation in the coding region. To our knowledge, this is the first case report of the coexistence of Kallmann syndrome and Dandy-Walker malformation in the same patient.
Exp Clin Endocrinol Diabetes 2004 Jan
PMID:A case of Kallmann syndrome associated with Dandy-Walker malformation. 1475 74

The olfactory bulb expresses one of the highest levels of insulin found in the brain. A high level of expression of the concomitant insulin receptor (IR) kinase is also retained in this brain region, even in the adult. We have previously demonstrated in a heterologous system that insulin modulates the voltage-dependent potassium channel, Kv1.3, through tyrosine phosphorylation of three key residues in the amino and carboxyl terminus of the channel protein. Phosphorylation also induces current suppression of the Kv1.3-contributed current in cultured olfactory bulb neurons (OBNs) of rodents. In order to explore the behavioral importance of this kinase-induced modulation of the channel for the olfactory ability of the animal, mice with a targeted-gene deletion of the insulin receptor were electrophysiologically and behaviorally characterized. Mice heterozygous for the insulin receptor kinase (IR+/-) gene performed the same as wild-type (+/+) mice when challenged with a traditional, non-learning-based task to test gross anosmia. There was also no significant difference across the two genotypes in tests designed to measure exploratory behavior or in a battery of systems physiology experiments designed to assess metabolic energy usage (locomotion, ingestive behaviors, weight, oxygen consumption, and respiratory quotient). Object memory recognition tests suggest that IR+/- mice have an impairment in recognition of familiarized objects; IR+/- mice demonstrate poor performance for both short-term (1 h) and long-term (24 h) memory tests in comparison to that of wild-type mice. Electrophysiological experiments indicate that mitral cell neurons cultured from both heterozygous and homozygous-null mice (IR+/- and IR-/-) have an decreased peak current amplitude compared with that recorded for wild-type (+/+) animals matched for days in vitro (DIV). These data indicate that the loss of one allele of the IR kinase gene modifies the electrical phenotype of the mitral cell neurons in the olfactory bulb without a change in gross olfactory ability. Given our findings that there are no significant changes in metabolic balance of the IR (+/-) mice but some impairment in memory retention, future experiments testing for specific olfactory behaviors or functional deficits in IR-/+ mice models of diabetes will need to either be tasks that do not require learning or will require a different model (such as diet-induced diabetes) that may evoke a stronger phenotype.
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PMID:Electrophysiological and behavioral phenotype of insulin receptor defective mice. 1617 26

Wolfram syndrome is a rare autosomal recessive neurodegenerative disease; it is characterized by the appearance of diabetes mellitus in childhood associated with bilateral optic atrophy that often leads to blindness. Insipid diabetes, deafness, psychiatric disorders, anosmia, anomalies of the urinary tract, nystagmus, ataxia, and myoclonias are less frequent. We report two cases of Wolfram syndrome, diagnosed in a 12-year-old girl and a 13-year-old boy. In each case, there was a history of diabetes mellitus; they consulted for a progressive loss of vision. Ophthalmologic examination objectified that visual acuity was reduced to finger counting in both eyes as well as isolated bilateral optic atrophy and constriction of the peripheral visual field. Through these two cases and a review of the literature, we propose to study the genetic and clinical aspects of Wolfram syndrome.
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PMID:[Two cases of Wolfram syndrome]. 1764 50

Smell (olfactory) and taste (gustatory) are key senses in the regulation of nourishment and individual safety. Olfactory and gustatory dysfunctions have been infrequently reported together in patients following stroke (Landis et al., 2006; Leopold et al., 2006). This case report details two patients who experienced smell and taste dysfunction following minor stroke events. Symptoms reported included hyposmia (diminished sense of smell) and anosmia (complete loss of smell), and dysgeusia (distorted taste). Patients' sense of smell and taste were assessed in an ambulatory care stroke prevention clinic eight months following their strokes. Patient A presented with minor stroke due to a lesion in the anterior circulation, patient B with a lesion in the posterior circulation. Both patients reported intense olfactory and gustatory dysfunction immediately following their strokes. Examination revealed a general inability to detect subtle odours and the ability to identify only 'sweet' tastes for both patients. In addition, both patients reported heavily salting or sweetening their food to mask the distorted and unpleasant taste, which also impacted comorbid conditions such as hypertension and diabetes. Patients and their spouses reported a decrease in their appreciation of family-related activities due to the patients' olfactory and gustatory dysfunction. Patients reported weight loss, lack of energy and strength, likely due to poor nutrition. Olfactory and gustatory dysfunctions are potentially deleterious outcomes following minor stroke and should be assessed by health care professionals prior to patient discharge. Assistance may be required to promote the health and well-being of patients and their carers if smell and taste are impacted by the stroke event.
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PMID:Smell and taste dysfunction following minor stroke: a case report. 1864 78


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