Fabry Disease Research Articles

Epidemiology and early predictors of Fabry nephropathy: evaluation of long-term outcomes from a national Fabry centre.

Fabry disease is a rare genetic lysosomal storage disorder, whereby the accumulation of sphingolipids consequently leads to kidney structural damage and dysfunction. We explored the epidemiology of chronic kidney disease (CKD) among patients with Fabry disease at a major UK referral centrein Greater Manchester serving over 7 million people, to inform early predictors of kidney disease and possible treatment planning. Data were sourced from the electronic records of registered participants from November 2020 to February 2022 of adults diagnosed with Fabry disease, with at least 1year of follow-up. Four hundred and five participants (female = 223, male = 182) met the initial eligibility criteria. Our study focused on identifying factors linked to incident CKD, with 395 evaluable individuals undergoing outcome analysis over a median of 6.4years. Findings concluded that 60.5% of participants received disease-modifying treatments, 29.7% experienced non-fatal cardiovascular events, 3.3% developed end-stage kidney disease (ESKD), and 7.3% died. Men had higher useof disease modifying therapy, progression to ESKD requiring kidney replacement therapy, cardiovascular events, and mortality compared to women. Subgroup analysis over 9years revealed that older age, cardiovascular history, renin-angiotensin-aldosterone system inhibitor use, and higher urine albumin-to-creatinine ratio (uACR) were predictors of faster estimated glomerular filtration rate (eGFR) decline and increased mortality. At baseline, 47.8% of 249 patients with uACR data had CKD, and 25.4% of the remaining individuals developed CKD during follow-up, associated with higher uACR and lower, albeit normal eGFR levels. Over 60% of Fabry disease patients are at lifetime risk of developing CKD, with a substantial risk of mortality, even with initially normal uACR and eGFR values.

UPLC-MS/MS High-Risk Screening for Sphingolipidoses Using Dried Urine Spots

Background: Early detection of sphingolipidoses is crucial to prevent irreversible complications and improve patient outcomes. The use of urine samples dried on filter paper (DUS) is a non-invasive strategy that simplifies the collection, storage, and shipping of samples compared to using liquid urine specimens. Objectives: (1) Develop and validate a multiplex ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) methodology using DUS to quantify twenty-one lysosphingolipids normalized to creatinine for eight different sphingolipidoses. (2) Establish normal reference values to evaluate the clinical utility of the methodology. Methods: Samples were eluted from a 5 cm filter paper disk (~1 mL of urine) and extracted on Oasis MCX solid-phase extraction cartridges prior to injection in the UPLC-MS/MS system. Results: Urinary lysosphingolipids were stable on DUS at −80 °C and −30 °C for 117 days, at 21.5 °C and 4 °C for at least 26 days, and at 35 °C for 3 days. Globotriaosylsphingosine, glucosylsphingosine, and their analogs were elevated in patients with Fabry disease and Gaucher disease, respectively, compared to controls (p-value < 0.0001). The analysis of related analog profiles suggests a better overall reliability in detecting patients early, especially for Fabry patients. Conclusions: This approach is feasible and might be useful for the early detection, monitoring, and follow-up of patients with sphingolipidoses.

Influence of Treatment Effect Modifiers in Fabry Disease: A Systematic Literature Review.

Fabry disease (FD) is a rare metabolic disorder which presents with considerable heterogeneity in disease characteristics. Given the absence of interventional studies comparing all available treatments, it is important for indirect treatment comparisons (ITCs) to account for potential treatment effect modifiers (TEMs). This systematic literature review (SLR) aimed to identify patient characteristics that may impact clinical outcomes by analyzing real-world evidence (RWE) in FD. An SLR was conducted according to PRISMA guidelines, with searches performed in the EMBASE, MEDLINE, and Cochrane databases (1946-2022; with a recent update in April 2023). Full-text articles reporting clinical outcomes from RWE studies of pharmacological therapies for the treatment of FD were included. Including studies from the recent SLR update, a total of 119 original studies met the PICOS criteria and 25 studies provided insights into TEMS. Potential TEMs in FD were identified: sex, age, timing of treatment initiation (early/delayed), left ventricular hypertrophy (LVH), estimated glomerular filtration rate (eGFR), proteinuria, presence of anti-drug-antibodies (ADAs) at baseline, and previous enzyme replacement therapy (ERT). In three studies (two including ERT-treated patients and one study of migalastat-treated patients) males showed worse renal outcomes than females. Five studies found that younger patients and those who received initial ERT before the age of 25years had greater reductions in plasma-lysoGb3, as well as more favorable renal, cardiac, and biochemical outcomes. Seven studies identified associations between LVH and reduced eGFR at baseline, along with an increased risk of cardiovascular, renal, and neurological events. In four studies, lower baseline eGFR and proteinuria were associated with faster annual eGFR decline despite ERT; high baseline proteinuria was a significant predictor of renal disease progression. Baseline ADAs were linked to lower eGFR, increased left ventricular mass, and reduced treatment impact on plasma/urine-lysoGb3. Migalastat was effective in treatment-naïve patients, while those previously treated with ERT experienced deteriorations in mean lysoGb3, eGFR, and left ventricular mass. This SLR highlighted several patient characteristics that influence treatment effectiveness in FD. It is important to account for these characteristics in ITCs to ensure unbiased outcomes.

Effects of Current Therapies on Disease Progression in Fabry Disease: A Narrative Review for Better Patient Management in Clinical Practice.

Fabry disease (FD) is a rare lysosomal storage disorder that is characterized by renal, neurological, and cardiovascular dysfunction. Four treatments are currently available for patients with FD; three enzyme replacement therapies (ERTs; agalsidase alfa, agalsidase beta, and pegunigalsidase alfa) and one pharmacological chaperone (migalastat). This review focuses on the evidence for the benefits of ERTs and migalastat, and provides an overview of their impact on disease manifestations and quality of life (QoL). Agalsidase beta is associated with renal, neurological, and cardiovascular benefits, and may prevent renal disease progression. Agalsidase alfa provides stabilizing effects across all main organ systems, although minor sex-specific differences exist in patients with more advanced baseline disease. The benefits of agalsidase alfa and agalsidase beta are similar but depend on the extent of baseline disease. Some data indicate that agalsidase beta may be preferable over the longer term. Both agalsidase alfa and agalsidase beta are associated with improved gastrointestinal and pain symptoms, as well as improved QoL. Patients with advanced end-organ damage tend not to respond as optimally to ERTs as those who initiate ERTs before irreversible organ fibrosis develops, highlighting the need for early treatment initiation. Migalastat, which is only approved for patients with amenable missense gene variants, generally stabilizes renal parameters and provides cardiovascular benefits. Migalastat also improves diarrhea and pain, and stabilizes QoL (although ERT may be more effective for pain management), but the neurological effects of migalastat have not been studied. Real-world data raise concerns about effective in vivo amenability of some genetic variants. Future studies with direct treatment comparisons in patients with FD are needed.

Organization of Nursing Care for Patients with Fabry Disease: From Molecular Foundations to Practical Solutions

Fabry disease is a rare X-linked inherited disorder that requires a comprehensive approach to medical care. This article examines the molecular mechanisms underlying the disease and their impact on the organization of nursing care, alongside practical experience in managing patients with this condition.

Pharmacokinetic evaluation of single-dose migalastat in non-Fabry disease subjects with ESRD receiving dialysis treatment, and use of modeling to select dose regimens in Fabry disease subjects with ESRD receiving dialysis treatment.

Fabry disease (FD) is an X-linked lysosomal disorder leading to multiorgan dysfunction, including renal impairment and the risk of significant accumulation for renally excreted drugs. Migalastat, an approved therapy in FD patients with amenable variants, is primarily eliminated in urine; however, its use had not been studied in patients with end-stage renal disease (ESRD) receiving dialysis therapy. This study investigated the pharmacokinetics (PK), dialyzability, and tolerability of 123 mg migalastat in non-FD subjects with ESRD on stable hemodialysis/hemodiafiltration (EudraCT 2018-003684-57). Results were analyzed by population PK and physiologically based PK (PBPK) modeling and intended to propose dose regimens resulting in negligible migalastat trough levels in plasma and comparable concentrations above the threshold in target tissues in FD patients with ESRD. Subjects with ESRD received 123 mg migalastat 24 hours before dialysis and, following an 8-day washout, immediately before dialysis. Matched controls with normal renal function (NRF) received migalastat 123 mg. Migalastat concentrations were measured in plasma, urine, and dialysate, and modeled to select regimens providing similar disposition to NRF. Migalastat was extracted by hemodialysis/hemodiafiltration (74%/72%). PBPK modeling predicted that 123 mg every other week (QOW) with regular dialysis 2-3 times weekly in ESRD subjects produced: a fraction of time above EC50 similar to FD patients with NRF; adequate Cmax for intracellular trafficking of mutant α-galactosidase A to the lysosome; and Ctrough levels near the lower limit of quantification (LLOQ) similar to NRF subjects receiving 123 mg every other day. Migalastat 82 mg weekly produced a greater fraction of time above EC50 and longer duration of concentrations above the LLOQ, potentially resulting in accumulation in tissues. Migalastat was well extracted by hemodialysis/hemodiafiltration. Migalastat 123 mg QOW is the proposed dose regimen for further evaluation in FD patients with ESRD, which could inform expansion of treatment options. Trial registration: EU Clinical Trials Register, EudraCT number 2018-003684-57.

Role of Longitudinal Strain in the Evaluation of Contractile Dysfunction in Japanese Fabry Disease Patients.

Fabry disease is a hereditary metabolic disorder caused by a decrease in or deficiency of the lysosomal enzyme α-galactosidase A. Enzyme replacement therapy or pharmacological chaperone therapy can improve prognosis, especially in patients in the early phase of cardiac involvement. Longitudinal strain (LS) evaluated using speckle tracking echocardiography can detect early contractile dysfunction. However, there have been no reports of LS in Japanese Fabry disease patients. We recruited 56 patients with Fabry disease (22 men, 34 women) who were followed up at Jikei University Hospital. Fifty-eight control subjects without overt cardiac diseases were also included in the study. We evaluated LS in each patient, and the values of each of the 17 segments of the left ventricle (LV) were averaged, and global LS (GLS) was also calculated. GLS was significantly worse in Fabry disease patients without LV hypertrophy than in control subjects (-18.5±2.8% vs. -20.4±1.6%; P<0.05). In addition, Fabry disease patients without LV hypertrophy had significantly worse lateral LS (-16.4±5.0% vs. -19.3±1.8%; P<0.05), basal LS (-16.5±3.2% vs. -18.5±1.7%; P<0.05), and mid LS (-18.7±1.7% vs. -20.8±1.6%; P<0.05) than control subjects. These results suggest that early contractile dysfunction in Fabry disease can be observed using GLS, lateral LS, basal LS, and mid LS, even without LV hypertrophy.

Clinical features and quality of life in patients with Fabry disease

To explore the clinical characteristics of patients with Fabry disease (FD) and the potential influencing factors, as well as to analyze the main factors affecting the quality of life (QOL) of FD patients. The clinical data of 21 adult FD patients who were hospitalized and treated at the University of Hong Kong-Shenzhen Hospital from January 2022 to December 2023 were retrospectively analyzed, including questionnaire data from 17 of these patients. The total score of the Short Form 36 Health Survey (SF-36) was used to determine the QOL. The patient's average age was (42±9) years, including 13 males (61.9%). All patients belonged to 17 families and had a total of 14 gene mutation types. The c.640-801G>A mutation was the most common type, found in 4 patients (19.0%), with cardiac damage as the primary manifestation. The c.901C>T mutation led to lesions in the heart, brain, and kidneys, and early onset and severe phenotypes were detected in female patients. Male patients had lower total SF-36 scores than females (P<0.05). Patients with proteinuria, stroke, hypohidrosis/anhidrosis, and cardiac insufficiency had lower total SF-36 scores compared with those without these symptoms (all P<0.05). The current study indicates that the clinical phenotypes of patients with FD are influenced by a combination of gender, genotype, and non-genetic factors, and gender and clinical symptoms serve as the primary factors affecting patient's QOL.

A 1-Bag/4-Step Rapid Desensitization Protocol to Reintroduce Agalsidase a in a Patient With Fabry Disease.

A 1-Bag/4-Step Rapid Desensitization Protocol to Reintroduce Agalsidase a in a Patient With Fabry Disease.

Genotype-Phenotype Spectrum of 52 Mexican Patients With Fabry Disease: A Novel GLA Variant With Atypical Phenotype.

Fabry disease (FD) is a rare lysosomal type 3 disorder with an X-linked inheritance pattern caused by pathogenic variants in the GLA gene. This study aimed to describe the genotype and phenotype of 52 Mexican patients with FD. We included 12 patients with clinical and molecular diagnosis of FD treated at our institution and 40 FD Mexican patients already reported in the literature. The most frequent manifestations were acroparesthesias (71.2%), hypohidrosis or anhidrosis (48.1%), heat intolerance (46.2%), and proteinuria (42.3%). Renal and neurological manifestations were more prevalent in males than females. Cardiac involvement included hypertrophic cardiomyopathy and Wolf-Parkinson-White arrhythmia. Cornea verticillata was seen in 14 patients (26.9%) and angiokeratomas in 15 (28.8%). We identified 14 variants in the GLA gene in Mexican patients with FD. We found a novel variant GLA c.122C>G that causes an atypical FD phenotype with predominantly neurological involvement in two unrelated patients, one of them with a forthright clinical and radiological overlap of Multiple Sclerosis and normal biological biomarkers, thus requiring a renal biopsy that helped confirm the diagnosis of FD. The genotype and phenotype of Mexican patients with FD are similar to other populations. Atypical phenotype of FD, such as the one associated with the novel variant c.122C>G, can be a diagnostic challenge, as it can be mixed up with MS. Our findings confirm the limitations of noninvasive diagnostic methods and the necessity of the renal biopsy when the clinical suspicion of FD is high.

The use of nanocarriers in treating Batten disease: A systematic review.

The neuronal ceroid lipofuscinoses, commonly known as Batten disease, are a group of lysosomal storage disorders affecting children. There is extensive central nervous system and retinal degeneration, resulting in seizures, vision loss and a progressive cognitive and motor decline. Enzyme replacement and gene therapies are being developed, and mRNA and oligonucleotide therapies are more recently being considered. Overcoming the challenges of the blood-brain barrier and blood-ocular barrier is crucial for effectively targeting the brain and eye, whatever the therapeutic approach. Nanoparticles and extracellular vesicles are small carriers that can encapsulate a cargo and pass through these cell barriers. They have been investigated as drug carriers for other pathologies and could be a promising treatment strategy for Batten disease. Their use in gene, enzyme, or mRNA replacement therapy of all lysosomal storage disorders, including Mucopolysaccharidoses, Niemann-Pick diseases, and Fabry disease, is investigated in this systematic review. Different nanocarriers can efficiently target the lysosome and cross the barriers into the brain and eyes. This supports continued exploration of nanocarriers as potential future treatment options for Batten disease.

Relevance of Neutralizing Antibodies for the Pharmacokinetics of Pegunigalsidase Alfa in Patients with Fabry Disease.

Pegunigalsidase alfa is a newly approved drug for the treatment of Fabry disease, designed to increase the plasma half-life and reduce immunogenicity of infused α-galactosidase A (AGAL). We provide the first comprehensive pharmacokinetic and immunogenic data apart from industry-initiated studies. Pharmacokinetics of pegunigalsidase alfa, amino acid, and polyethylene glycol (PEG)-specific antibodies and immunecomplexes were measured in treated patients (11 switched, two naïve). Measurements were performed in serum samples drawn directly before and after infusions over three to ten consecutive infusions. Only three patients started directly with 1.0 mg/kg body weight. No infusion-associated reactions were reported under pegunigalsidase alfa during the observation. Patients without pre-existing neutralizing anti-AGAL antibodies showed high enzymatic AGAL peak activities and sustained AGAL serum concentrations until the next infusion, which was not observed in those with neutralizing anti-AGAL antibodies. Nine (69.2%) patients presented with pre-existing anti-PEG antibodies (IgG or IgM), which seemed to have no impact on pharmacokinetics during the observation. No new anti-PEG or anti-AGAL antibody formation was observed after treatment initiation. Three (75.0%) patients with pre-existing neutralizing anti-AGAL antibodies showed a titer increase and one (25.0%) patient a decrease. In patients with anti-AGAL antibodies (n = 4) immune-complex formation was detected. The pharmacokinetics of pegunigalsidase alfa show different profiles depending on the presence of pre-existing neutralizing antibodies, with reduced plasma half-life and peak enzyme activity after infusion in patients with antibodies. The clinical significance of a reduced pegunigalsidase alfa half-life and the formation of immune complexes in antibody-positive patients needs to be analyzed in future studies.

Long-read sequencing enables comprehensive molecular genetic diagnosis of Fabry disease

BackgroundThe clinical diagnosis of Fabry Disease (FD) can be challenging due to the clinical heterogeneity, especially in females. Patients with FD often experience a prolonged interval between the onset of symptoms and receiving a diagnosis. Genetic testing is the gold standard for precise diagnosis of FD, however conventional genetic testing could miss deep intronic variants and large deletions or duplications. Although next-generation sequencing, which analyzes numerous genes, has been successfully used for FD diagnosis and can detect complex variants, an effective and rapid tool for identifying a wide range of variants is imminent, contributing to decrease the diagnostic delay.MethodsThe comprehensive Analysis of FD (CAFD) assay was developed for FD genetic diagnosis, employing long-range PCR coupled with long-read sequencing to target the full-length GLA gene and its flanking regions. Its clinical performance was assessed through a comparative analysis with Sanger sequencing.ResultsGenetic testing was performed on 82 individuals, including 48 probands and 34 relatives. The CAFD assay additionally identified variants in two probands: one had a novel and de novo pathogenic variant with a 1715 bp insertion in intron 4, and the other carried two deep intronic VUS variants in cis-configuration also in intron 4. In total, CAFD identified 47 different variants among 48 probands. Of these, 42 (89.36%, 42/47) were pathogenic, while 5 (10.64%, 5/47) were VUS. Sixteen (34.04%, 16/47) of the variants were novel, including 15 SNV/Indels and one large intronic insertion. Pedigree analysis of 21 probands identified four de novo disease-causing variants. Hence, FD exhibits not only variable clinical presentations but also a wide spectrum of variants. Utilizing a comprehensive testing algorithm for diagnosing FD, which includes enzyme activity, clinical features, and genetic testing, the diagnostic yield of CAFD is 97.92% (47/48), which is higher than that of conventional Sanger sequencing, at 95.83% (46/48).ConclusionThe duration between initial clinical presentation and diagnosis remains long and winding. CAFD provides precise diagnosis for a wide spectrum of GLA variants, promoting timely diagnosis and appropriate treatment for FD patients.

Case Report: The tree that hides the forest, a case of renal ANCA vasculitis concurrent with Fabry nephropathy.

This case report presents a complex case of a 65-year-old female with a history of hypertension and a family history of polycystic kidney disease and Fabry disease presented with acute pancreatitis and subsequent renal insufficiency. Despite initial corticosteroid therapy for immuno-allergic nephropathy, the patient’s condition deteriorated with the development of a skin rash, uremic syndrome, and neurological symptoms. A renal biopsy revealed cellular crescents and cytoplasmic vacuolization in podocytes and tubular cells. Genetic testing confirmed a GLA gene mutation, consistent with Fabry disease. While undergoing treatment with cyclophosphamide, the patient experienced severe allergic reactions, ultimately leading to acute respiratory distress syndrome and fatal outcome. Despite the Fabry disease variant being primarily associated with cardiac involvement, renal involvement was evident. This case highlights the rarity of this co-occurrence, the diagnostic challenges, the importance of genetic factors in autoimmune kidney diseases, and the impact of drug allergies on patient management.

Zebra Bodies on Renal Biopsy: Fabry Disease or Not Fabry? A Tale of Two Cases

Background: Zebra bodies are intracellular lamellar inclusions detected by electron microscopy (EM) on renal biopsy, classically found in Fabry disease. This EM finding prompts genetic testing for α-galactosidase A enzyme deficiency to diagnose Fabry disease, and thus consider enzyme replacement therapy. Zebra bodies have also been associated with certain medications, including statins and hydroxychloroquine. We present two contrasting cases, both presented within a year of each other with zebra bodies found in renal biopsy. Case Presentations Case 1: An 83-year-old lady with type II diabetes mellitus and hypertension was presumed to have diabetic or hypertensive nephropathy, however in ruling out alternative causes, was found to have asymptomatic myeloma. Renal biopsy to detect renal amyloidosis or myeloma kidney instead found zebra bodies on EM. Genetic testing confirmed Fabry disease. She was managed conservatively. Case 2: This contrasts with an 80-year-old woman with rapid decline in her renal function following coronary angiography. Renal biopsy showed hypertensive nephropathy on light microscopy, and zebra bodies on EM. She tested negative for Fabry disease. She was taking sertraline, and had previously been on atorvastatin, but this had been stopped four years prior to the biopsy. Conclusion: Drug-induced renal phospholipidosis is an important differential diagnosis to be considered in cases with zebra bodies that are negative for Fabry disease. It is unclear for how long a patient needs to be taking a culprit medication to develop these changes, and whether they may persist many years later. From our findings, it is clear that more research is needed to identify alternative causes of zebra bodies to guide earlier diagnosis and treatment, which would improve outcomes.

Changes in peak oxygen consumption in Fabry disease and associations with cardiomyopathy severity

BackgroundFabry disease (FD) causes multiorgan sphingolipid accumulation, with cardiac involvement responsible for the largest burden of morbidity and mortality. Exercise intolerance in FD is prevalent, yet the mechanisms of this...

Anderson–Fabry Disease: Focus on Ophthalmological Implications

Anderson–Fabry Disease: Focus on Ophthalmological Implications

Endocannabinoid receptor 2 is a potential biomarker and therapeutic target for the lysosomal storage disorders.

Herein, we studied the expression of endocannabinoid receptor 2 (CB2R), a known inflammation mediator, in several lysosomal storage disorder (LSD) animal models and evaluated it as a potential biomarker and therapeutic target for these diseases. CB2R was highly elevated in the plasma of Farber disease and mucopolysaccharidosis (MPS) type IIIA mice, followed by Fabry disease and MPS type I mice. Mice with acid sphingomyelinase-deficient Niemann-Pick disease (ASMD) and rats with MPS type VI exhibited little or no plasma CB2R elevation. High-level expression of CB2R was also observed in tissues of Farber and MPS IIIA mice. Treatment of MPS IIIIA patient cells with CB2R agonists led to a reduction of CB2R and monocyte chemoattractant protein-1 (MCP-1), a chemotactic factor that is elevated in this LSD. Treatment of MPS IIIA mice with one of these agonists (JWH133) led to a reduction of plasma and tissue CB2R and MCP-1, a reduction of glial fibrillary acidic protein (GFAP) in the brain, and an improvement in hanging test performance. JWH133 treatment of Farber disease mice also led to a reduction of MCP-1 in tissues and plasma, and treatment of these mice by enzyme replacement therapy (ERT) led to a reduction of plasma CB2R, indicating its potential to monitor treatment response. Overall, these findings suggest that CB2R should be further examined as a potential therapeutic target for the LSDs and may also be a useful biomarker to monitor the impact of therapies.

Role of Circulating X-Chromosome Inactivation and Xist as Biomarkers in Female Carriers of Fabry Disease

Role of Circulating X-Chromosome Inactivation and Xist as Biomarkers in Female Carriers of Fabry Disease

Screening for Fabry disease in patients with hypertrophic cardiomyopathy using cardiac magnetic resonance imaging.

Fabry disease (FD) usually mimics hypertrophic cardiomyopathy (HCM). Decreased native T1 mapping and a unique late gadolinium enhancement (LGE) pattern by cardiac magnetic resonance (CMR) imaging are specific imaging markers for FD. Explore the performance of multiparametric CMR imaging in screening for FD in patients with a HCM phenotype. A prospective cohort of 602 patients with a HCM phenotype was assessed from April 2012 to December 2022. Participants underwent CMR imaging and genetic testing. FD diagnosis was according to genetic testing and enzyme-activity test of α-galactosidase A. Multiparameter CMR imaging included cardiac function, native T1 mapping, extracellular volume (ECV), T2 mapping, LGE, and myocardial strains. Diagnostic performance of CMR parameters in identifying FD from HCM was done by analysis of receiver operating characteristic (ROC) curves. FD prevalence was 1.8% (11 cases) in this cohort with HCM. Native T1 mapping was significantly lower in FD compared with HCM (FD vs. HCM: native T1 mapping: 1174.08 ± 60.60 vs. 1293.94 ± 55.86, p < 0.001). Ventricular function, mass, ventricular wall thickness, and strains did not show significant differences between the two groups. Binary logistic regression and analysis of ROC curves demonstrated myocardial native T1 mapping of the left ventricular basal slice had the best performance in screening for FD in patients with a HCM phenotype (cutoff: 1216 ms; AUC: 0.947; sensitivity: 91%; specificity: 90%). Native T1 mapping is the best parameter for screening FD in a Chinese population with a HCM phenotype. Question The prevalence of Fabry Disease (FD) in the study population is unknown and the efficacy of cardiac MRI (CMR) parameter screening for FD needs validating. Findings We report the prevalence of FD among a Chinese hypertrophic cardiomyopathy (HCM) cohort and found T1 mapping is the best CMR parameter for screening FD. Clinical relevance Native T1 mapping is the best CMR parameter for screening FD in the HCM cohort, providing an effective method for rapid screening of FD in clinic, which may help identify patients for early treatment of FD.