Kearns-Sayre syndrome presenting as isolated growth failure

Holloman, Conisha; Wolfe, Lynne A.; Gahl, William A.; Boerkoel, Cornelius F.

doi:10.1136/bcr-2012-007272

Cited by 10 publications

(4 citation statements)

References 17 publications

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“…The patient was diagnosed with KSS based on the typical pathological results and clinical manifestations. Previous reports have described endocrine disorders, including insulin‐dependent diabetes mellitus, hypothyroidism, hypoparathyroidism and nonautoimmune Addison's disease, accompanying KSS (Holloman et al., ; Obara‐Moszynska et al., ; Quade et al., ), but there are no reports of their coexistence in a male with KSS.…”

Section: Discussionmentioning

confidence: 99%

“…KSS is caused by mtDNA rearrangements, and more than 150 different mtDNA deletions have been found to cause this syndrome (Holloman et al., ; Obara‐Moszynska et al., ). However, no mtDNA mutation was detected in blood cells collected from this patient.…”

Section: Discussionmentioning

confidence: 99%

“…KSS is classically characterised by disease onset before the age of 20, chronic progressive external ophthalmoplaegia, retinal pigmentary degeneration and at least one of the following: cardiac conduction block, neurological abnormalities or an elevated cerebrospinal fluid protein concentration. Endocrine disorders have been observed in patients with KSS, including those with growth hormone (GH) deficiency, hypoparathyroidism, hypothyroidism, insulin‐dependent diabetes mellitus (De Sanctis, Calzolari, Piazzi, & Berio, ; Ho, Pacaud, Rakic, & Khan, ; Holloman, Wolfe, Gahl, & Boerkoel, ) and nonautoimmune Addison's disease (Boles, Roe, Senadheera, Mahnovski, & Wong, ). Hypogonadism has also been reported in a previous study of mitochondrial myopathies, but the authors did not clarify whether hypogonadism was detected in association with KSS (Quade, Zierz, & Klingmuller, ).…”

Section: Introductionmentioning

confidence: 99%

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A case of hypopituitarism accompanying Kearns-Sayre syndrome treated with human chorionic gonadotropin: A case report and literature review

et al. 2016

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Kearns-Sayre syndrome (KSS) is a disorder caused by mutations in mitochondrial DNA. Here, we report an unusual case of Kearns-Sayre syndrome accompanied by hypopituitarism (deficiencies in reproductive and growth hormones). A 20-year-old male presented with growth retardation for the last 8 years, as well as the following findings: short stature, delayed puberty, myasthenia, an extraocular movement deficit, drooping eyelids, pectus carinatum and scoliosis. Cerebral enhanced magnetic resonance imaging revealed dysplasias of the pituitary, white matter and cerebellum. Laboratory work-up showed subnormal testosterone and growth hormone levels, a subnormal testicular volume, sensorineural deafness, pigmentary retinopathy, complete right bundle branch block and left anterior bundle branch block. Pathological examination revealed ragged red muscle fibres. Thus, this rare case involved the coexistence of Kearns-Sayre syndrome and hypopituitarism in a patient. Administration of coenzyme Q10 for the KSS and hormone replacement therapy for the endocrinopathies were performed for treatment of this patient.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A case of hypopituitarism accompanying Kearns-Sayre syndrome treated with human chorionic gonadotropin: A case report and literature review

et al. 2016

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“…Adenosine triphosphate (ATP) provides energy to drive different processes in the cells. The ATP levels in patients with KSS are reported to be disturbed, and alterations in intracellular ATP production is classically the main energy defect detected in these patients [ 24 ]. Interestingly, in the current study, we found no change in ATP levels in PBMNC derived iPSC of both KSS patients compared to iPSC from PBMNC of healthy individuals ( Figure 4 A).…”

Section: Resultsmentioning

confidence: 99%

Generation and Evaluation of Isogenic iPSC as a Source of Cell Replacement Therapies in Patients with Kearns Sayre Syndrome

Sequiera

Srivastava

Alagarsamy

et al. 2021

Cells

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Kearns Sayre syndrome (KSS) is mitochondrial multisystem disorder with no proven effective treatment. The underlying cause for multisystem involvement is the energy deficit resulting from the load of mutant mitochondrial DNA (mtDNA), which manifests as loss of cells and tissue dysfunction. Therefore, functional organ or cellular replacement provides a promising avenue as a therapeutic option. Patient-specific induced pluripotent stem cells (iPSC) have become a handy tool to create personalized cell -based therapies. iPSC are capable of self-renewal, differentiation into all types of body cells including cardiomyocytes (CM) and neural progenitor cells (NPC). In KSS patients, mutations in mtDNA are largely found in the muscle tissue and are predominantly absent in the blood cells. Therefore, we conceptualized that peripheral blood mononuclear cells (PBMNC) from KSS patients can be reprogrammed to generate mutation free, patient specific iPSC lines that can be used as isogenic source of cell replacement therapies to treat affected organs. In the current study we generated iPSC lines from two female patients with clinical diagnosis of classic KSS. Our data demonstrate that iPSC from these KSS patients showed normal differentiation potential toward CM, NPC and fibroblasts without any mtDNA deletions over passages. Next, we also found that functional studies including ATP production, reactive oxygen species generation, lactate accumulation and mitochondrial membrane potential in iPSC, CM, NPC and fibroblasts of these KSS patients were not different from respective cells from healthy controls. PBMNCs from these KSS patients in the current study did not reproduce mtDNA mutations which were present in muscle biopsies. Furthermore, we demonstrate for the first time that this phenomenon provides opportunities to create isogenic mutation free iPSC with absent or very low level of expression of mtDNA deletion which can be banked for future cell replacement therapies in these patients as the disease progresses.

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Cellular and Molecular Responses to Mitochondrial DNA Deletions in Kearns-Sayre Syndrome: Some Underlying Mechanisms

Yazdani

2024

Mol Neurobiol

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Kearns-Sayre syndrome presenting as isolated growth failure

Cited by 10 publications

References 17 publications

A case of hypopituitarism accompanying Kearns-Sayre syndrome treated with human chorionic gonadotropin: A case report and literature review

A case of hypopituitarism accompanying Kearns-Sayre syndrome treated with human chorionic gonadotropin: A case report and literature review

Generation and Evaluation of Isogenic iPSC as a Source of Cell Replacement Therapies in Patients with Kearns Sayre Syndrome

Cellular and Molecular Responses to Mitochondrial DNA Deletions in Kearns-Sayre Syndrome: Some Underlying Mechanisms

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