The D313Y genotype—Pathogenic mutation or polymorphism?

Oder, Daniel; Wanner, Christoph; Nordbeck, Peter

doi:10.1111/cge.13237

Cited by 9 publications

(10 citation statements)

References 5 publications

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“…What is more, the Gb3 load in PBMC decreases with long-term ERT and could potentially be used for disease monitoring. It is important to highlight that this method failed to detect Gb3 deposits in non-classical/missense mutations, in particular in four patients with D313Y mutation, which are known to be non-disease-causing mutations 20…”

Section: Introductionmentioning

confidence: 99%

Hot topics in Fabry disease

Cairns

Müntze

Gernert

et al. 2018

Postgraduate Medical Journal

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Fabry disease is a rare inborn error of the enzyme α-galactosidase (α-Gal) and results in lysosomal substrate accumulation in tissues with a wide range of clinical presentations. The disease has attracted a lot of interest over the last years, in particular since enzyme replacement therapy (ERT) has become widely available in 2001. With rising awareness and rising numbers of (diagnosed) patients, physicians encounter new challenges. Over 900 α-Gal gene mutations are currently known, some with doubtful clinical significance, posing diagnostic and prognostic difficulties for the clinician and a lot of uncertainty for patients. Another challenge are patients who develop neutralising antibodies to ERT, which possibly leads to reduced therapy effectiveness. In this article, we summarise the latest developments in the science community regarding diagnostics and management of this rare lysosomal storage disorder and offer an outlook to future treatments.

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Section: Introductionmentioning

confidence: 99%

Hot topics in Fabry disease

Cairns

Müntze

Gernert

et al. 2018

Postgraduate Medical Journal

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“…Thus it has been questioned whether patients with the p.D313Y variant should be diagnosed with FD at all. [6][7][8]32 In a recent study, however, we report p.D313Y patients to have symptoms and organ manifestations comparable to classical FD. 9 While cerebrovascular involvement and cardiac hypertrophy as classical complications in FD could also be observed in our p.D313Y cohort, it should be considered that those conditions might represent coincidental findings that are not related to a FD manifestation.…”

Section: Discussionmentioning

confidence: 70%

“…Patients with a disease modifying variant, like p.D313Y, are biochemically different from classical Fabry patients, as they usually do not show elevated Gb3 levels that could be used as a sensitive and specific marker for the diagnosis of FD. Thus it has been questioned whether patients with the p.D313Y variant should be diagnosed with FD at all 6‐8,32 . In a recent study, however, we report p.D313Y patients to have symptoms and organ manifestations comparable to classical FD 9 .…”

Section: Discussionmentioning

confidence: 82%

“…The Mainz Severity Score Index (MSSI) 13 was determined in all patients. The total score is composed of four sections (general, neurological, cardiovascular and renal signs and symptoms) and its results are categorized by number of attained points as mild (≤18), moderate (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) or severe (>38). Overall, it has been shown that MSSI represents a useful tool for clinicians in evaluating the severity and progression of FD.…”

Section: Apart From the Pd313y Mutation Further Co-existing Classicalmentioning

confidence: 99%

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Assessment of small fiber neuropathy in patients carrying the non‐classical Fabry variant p.D313Y

et al. 2021

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Introduction The pathophysiological significance of the Fabry‐related, non‐classical variant p.D313Y still remains to be solved. This study assesses the involvement of the peripheral nervous system with respect to small fiber neuropathy and neuropathic pain in female patients carrying p.D313Y. Methods This study examined nine females carrying the Fabry‐related p.D313Y variant by obtaining skin punch biopsies above the right lateral malleolus. Intraepidermal nerve fiber density was determined for each patient and compared to reference values matched for the patientʼs decade of life and sex. Moreover, each patient was characterized by a detailed neurological examination and by pain assessment via questionnaire. Results Compared to sex‐matched lower fifth percentile reference values per decade, intraepidermal nerve fiber density was decreased in seven out of nine patients. Four patients reported acral paresthesias and neuropathic pain with an average visual analogue scale score of 7 out of 10 points. Two patients experienced acute pain crises. Six out of seven patients diagnosed with small fiber neuropathy had a their medical history of hypo‐ and/or hyperhidrosis. Discussion The diagnosis of small fiber neuropathy was made in seven out of nine females carrying the non‐classical variant p.D313Y. Moreover, neuropathic pain and symptoms indicative of autonomic nervous system dysfunction seem to be common findings that may be of clinical significance and may warrant therapeutic intervention.

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“…It was described as an efficient method for disease monitoring; however, this measurement on PBMCs was not reported as an excellent alternative to determine Gb3 deposits in patients with non-classical or missense mutations; in particular, the authors reported this finding in subjects with D313Y mutation. [12] To date, there are limited biomarkers of Fabry disease. The knowledge of the pathogenesis of tissue and organ dysfunction allows us to establish a relationship between a biomarker and the progression of the disease.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers in Anderson–Fabry Disease

Simonetta

Tuttolomondo

Daidone

et al. 2020

IJMS

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Fabry disease is a rare lysosomal storage disorder caused by a deficiency of α-galactosidase A, resulting in multisystemic involvement. Lyso-Gb3 (globotriaosylsphingosine), the deacylated form of Gb3, is currently measured in plasma as a biomarker of classic Fabry disease. Intensive research of biomarkers has been conducted over the years, in order to detect novel markers that may potentially be used in clinical practice as a screening tool, in the context of the diagnostic process and as an indicator of response to treatment. An interesting field of application of such biomarkers is the management of female heterozygotes who present difficulty in predictable clinical progression. This review aims to summarise the current evidence and knowledge about general and specific markers that are actually measured in subjects with confirmed or suspected Fabry disease; moreover, we report potential novel markers such as microRNAs. Recent proteomic or metabolomic studies are in progress bringing out plasma proteome profiles in Fabry patients: this assessment may be useful to characterize molecular pathology of the disease, to improve diagnostic process, and to monitor response to treatment. The management of Fabry disease may be improved by the identification of biomarkers that reflect clinical course, severity, and the progression of the disease.

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The D313Y genotype—Pathogenic mutation or polymorphism?

Cited by 9 publications

References 5 publications

Hot topics in Fabry disease

Hot topics in Fabry disease

Assessment of small fiber neuropathy in patients carrying the non‐classical Fabry variant p.D313Y

Biomarkers in Anderson–Fabry Disease

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