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Fabry disease (FD, OMIM 301500) is an X-linked disorder of glycosphingolipid metabolism resulting from the deficient activity of α-galactosidase A, a lysosomal acid hydrolase, leading to progressive lysosomal accumulation of incompletely metabolized neutral glycosphingolipids. Cardiac involvement is frequent. The objective of this study was to characterize the cardiac abnormalities in male patients affected with classic Fabry disease and define the context in which the clinicians were able to make the diagnosis. Clinical evaluation, laboratory tests, electrocardiography (ECG) and echocardiography were performed in 20 hemizygous men (mean age 39 years, range 12–65 years). The context of diagnosis was obtained by review of patients' charts. Left ventricular hypertrophy (LVH) and/or concentric remodeling were found in 12 patients (60%). Structural changes in mitral and aortic valves were found in 25% and 10% of cases, respectively. The sensitivity of the ECG Romhilt–Estes score for LVH was high (80%). Short PR interval (40%), ST segment abnormalities and conduction delay were frequent on ECG. Left ventricular mass index, ECG scores for LVH and systolic pulmonary pressure correlated positively with age. There was no relation between classic vascular risk factors and coronary artery disease, transient ischemic attack (TIA) or stroke. Diagnosis of Fabry disease was frequently suggested by nephrologists, dermatologists or geneticists. Echocardiograph and ECG abnormalities are frequently observed in patients with Fabry disease. Cardiologists should be aware of the diagnosis of Fabry disease in patients presenting with LVH, concentric remodeling, mitral and aortic valve thickening on echocardiography, short PR interval and conduction defects on ECG. [ABSTRACT FROM AUTHOR]

Fabry disease (FD) is an X-linked recessive inborn error of glycosphingolipid metabolism. Among clinical symptoms, maculopapular skin lesions, known as angiokeratoma, most often appear on the lower abdomen, scrotum, and thighs, with a tendency toward bilateral symmetry. A 30-year-old male patient was referred to us for evaluation of a complex vascular and cutaneous malformation. Skin examination showed numerous angiokeratoma, which had developed only on the right part of the body, with a sharp delineation in the midline of the trunk. The diagnosis of FD was confirmed by demonstration of a decreased α-galactosidase A activity, and the patient was shown to be hemizygote for a missense mutation (R342Q) in the α-galactosidase A gene (GLA). This mutation was also demonstrated in DNA extracted from fibroblast cultures established from both affected and unaffected skin areas, thus excluding the hypothesis of somatic mosaicism or revertant mosaicism. Interestingly, the diagnosis of Klippel–Trénaunay–Weber syndrome (KTWS) was also made, through clinical and radiological investigations. This is the first report on the association between FD and KTWS. Karyotype analysis was normal. It is likely that the mixed vascular malformations of KTWS affecting capillary and venous systems have contributed to the unusual angiokeratoma distribution pattern observed in the patient. [ABSTRACT FROM AUTHOR]

Aims: Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed., Methods: In 2014, experts met to discuss recent advances on this topic and update clinical guidance., Results: Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Würzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs., Conclusion: To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications., (© 2016 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Tetrasomy 9p is a generic term describing the presence of a supernumerary chromosome incorporating two copies of the 9p arm. Two varieties exist: isodicentric chromosome 9p (i(9p)), where the two 9p arms are linked by a single centromeric region, and pseudodicentric 9p (idic(9p)), where one active and one inactive centromere are linked together by a proximal segment of 9q that may incorporate euchromatic material. In living patients, i(9p) and idic(9p) are usually present in a mosaic state. Fifty-four cases, including fetuses, have been reported, of which only two have been molecularly characterized using array-CGH. Tetrasomy 9p leads to a variable phenotype ranging from multiple congenital anomalies with severe intellectual disability and growth delay to subnormal cognitive and physical developments. Hypertelorism, abnormal ears, microretrognathia and bulbous nose are the most common dysmorphic traits. Microcephaly, growth retardation, joint dislocation, scoliosis, cardiac and renal anomalies were reported in several cases. Those physical anomalies are often, but not universally, accompanied by intellectual disability. The most recurrent breakpoints, defined by conventional cytogenetics, are 9p10, 9q12 and 9q13. We report on 12 new patients with tetrasomy 9p (3 i(9p), 8 idic(9p) and one structurally uncharacterized), including the first case of parental germline mosaicism. All rearrangements have been characterized by DNA microarray. Based on our results and a review of the literature, we further delineate the prenatal and postnatal clinical spectrum of this imbalance. Our results show poor genotype-phenotype correlations and underline the need of precise molecular characterization of the supernumerary marker., (© 2015 Wiley Periodicals, Inc.)