scholarly journals The m.9143T>C Variant: Recurrent Infections and Immunodeficiency as an Extension of the Phenotypic Spectrum in MT-ATP6 Mutations?

Diseases ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 19
Author(s):  
Diana Lehmann Urban ◽  
Leila Motlagh Scholle ◽  
Matias Wagner ◽  
Albert C. Ludolph ◽  
Angela Rosenbohm
Keyword(s):  
Index Patient ◽  
Insulin Dependent Diabetes Mellitus ◽  
Clinical Feature ◽  
Dependent Diabetes Mellitus ◽  
Recurrent Infections ◽  
Pathogenic Variants ◽  
Atp6 Gene ◽  
Wide Range ◽  
T Cell Lymphopenia ◽  
Insulin Dependent

Pathogenic variants in the MT-ATP6 are a well-known cause for maternally inherited mitochondrial disorders associated with a wide range of clinical phenotypes. Here, we present a 31- year old female with insulin-dependent diabetes mellitus, recurrent lactic acidosis and ketoacidosis recurrent infections with suspected immunodeficiency with T cell lymphopenia and hypogammaglobulinemia as well as proximal tetraparesis with severe muscle and limb pain and rapid physical exhaustion. Muscle biopsy and respiratory chain activities were normal. Single-exome sequencing revealed a variant in the MT-ATP6 gene: m.9143T>C. Analysis of further specimen of the index and mother (segregation studies) revealed the highest mutation load in muscle (99% level of mtDNA heteroplasmy) of the index patient. Interestingly, acute metabolic and physical decompensation during recurrent illness was documented to be a common clinical feature in patients with MT-ATP6 variants. However, it was not mentioned as a key symptom. Thus, we suggest that the clinical spectrum might be expanded in ATP6-associated diseases.

Wolfram-like syndrome – another face of a rare disease in children

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Mariusz Smetek ◽  
Karolina Gadzalska ◽  
Paulina Jakiel ◽  
Julia Grzybowska ◽  
Malgorzata Mysliwiec ◽  
...  
Keyword(s):  
De Novo ◽  
Insulin Dependent Diabetes Mellitus ◽  
Wolfram Syndrome ◽  
Dependent Diabetes Mellitus ◽  
Single Mutation ◽  
Pathogenic Variants ◽  
Ophthalmologic Examination ◽  
Insulin Dependent ◽  
Type 1 Dm

Abstract Objectives The presence of two pathogenic variants in the WFS1 gene leads to the occurrence of a rare genetic disease in children – Wolfram syndrome (WFS), which includes insulin-dependent diabetes mellitus (DM), optic atrophy (OA), diabetes insipidus (DI), and deafness (D). However, the presence of a single mutation in the WFS1 gene results in a number of other autosomal dominant inherited diseases, including Wolfram-like syndrome (WFS-like). Case presentation A 10-year-old boy was referred to the Genetic Outpatient Clinic with suspected WFS based on the coexistence of D, type 1 DM, short stature, and abnormalities in ophthalmologic examination (astigmatism and OA due to the optical coherence tomography result). The genetic analysis did not confirm WFS syndrome in the boy but identified a single likely pathogenic de novo variant in the WFS1 gene, which confirmed WFS-like syndrome. Conclusions Currently, the patient is under the care of an endocrinologist, diabetologist, ophthalmologist, audiologist, and also psychologist because of mood disorders.

Elevated Circulating P-Selectin in Insulin Dependent Diabetes Mellitus

1996 ◽  
Vol 76 (03) ◽  
pp. 328-332 ◽  
Author(s):  
Bernd Jilma ◽  
Peter Fasching ◽  
Christine Ruthner ◽  
Anna Rumplmayr ◽  
Sabine Ruzicka ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Levels ◽  
Plasma Concentrations ◽  
Insulin Dependent Diabetes Mellitus ◽  
Interquartile Range ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Intergroup Comparison ◽  
Median Plasma ◽  
Insulin Dependent

SummaryBased on findings that showed increased P-selectin expression on platelets and on choroidal microvessels of patients with insulin dependent diabetes mellitus (IDDM), we hypothesized that also plasma concentrations of circulating (c)P-selectin would be increased in these patients.The aim of this study was to compare the plasma levels of cP-selec-tin between non-smoking patients with IDDM, treated with an intensified insulin therapy, and healthy controls. The study design was prospective, cross-sectional and analyst-blinded. Subjects were matched individually for sex, age and body mass index. Plasma levels of cP-selectin and of von Willebrand antigen (vWF-Ag) were determined by enzyme linked immunoassays.Forty-two pairs were available for intergroup comparison. Median plasma concentrations of cP-selectin in patients with IDDM (285 ng/ml; interquartile range: 233-372) were on average 21% higher than those of controls (236 ng/ml; interquartile range: 175-296; p = 0.004). Also, median plasma levels of vWF-Ag were 10% higher in patients (96 U/dl; interquartile range: 82-127) than controls (87 U/dl; interquartile range: 70-104; p = 0.025). There was no correlation between plasma concentrations of cP-selectin and vWF-Ag levels in either group (p ώ0.05).In conclusion, our results of increased cP-selectin levels are in line with increased P-selectin expression on platelets and on choroidal microvessels found in patients with IDDM. In view of the currently developed small molecule inhibitors of cell adhesion molecules, these independent observations together may provide a sound rationale to select P-selectin as a target for treating or preventing IDDM-associated micro- or macrovascular complications.

Insulin release and pancreatic insulin is reduced in young prediabetic BB rats

1986 ◽  
Vol 112 (3) ◽  
pp. 367-371 ◽  
Author(s):  
Annette Svenningsen ◽  
Thomas Dyrberg ◽  
Helle Markholst ◽  
Christian Binder ◽  
Åke Lernmark
Keyword(s):  
Insulin Release ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Content ◽  
Dependent Diabetes Mellitus ◽  
Clinical Onset ◽  
Pancreatic Insulin ◽  
Pancreatic Insulin Content ◽  
Bb Rats ◽  
Insulin Dependent ◽  
The Mean

Abstract. The pancreases of approximately 50 days old diabetes-prone BB/Hagedorn (BB/H) and of the genetically closely related, but non-diabetic BB w-subline (control BB) rats were perfused to determine the capacity of D-glucose to release insulin before the expected development of diabetes. The BB/H rats were from a colony with 82–84% incidence of insulin-dependent diabetes mellitus (IDDM) by 140 days of age. The total amount of insulin released from the BB/H rat pancreas during stimulation with 20 mmol/l D-glucose was reduced by nearly 50% (P <0.01). The initial peak of insulin release was similar between the two groups of animals, whereas the amount of insulin released during the second peak accounted for the diminished release (P < 0.01). The extractable pancreatic insulin was 30% (P < 0.05) less in the BB/H rats. Total insulin release expressed relative to the pancreatic insulin content, was therefore not different between the two groups. It is concluded that about 20–40 days before the mean age of clinical onset of IDDM in BB/H rats, the capacity to release insulin in response to D-glucose is reduced along with a diminished pancreatic insulin content. This abnormality seems to be preceded only by islet cell surface antibodies but not by insulitis.

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