Deficiency in the Screening Process of Fabry Disease: Analysis of Chronic Kidney Patients Not on Dialysis

Fabry Disease (FD), a rare and progressive, X-linked lysosomal storage disorder, is caused by mutations in the α-galactosidase A (GLA) gene which leads to enzymatic deficiency of GLA. Misdiagnosed and undiagnosed FD cases are common for the variable FD phenotype, ranging from asymptomatic and/or impairment of single organs, which is typically seen in females and in patients with late-onset mutation, to multiple organ disease, which is frequently found in males with classic GLA mutation. Consequently, for an early diagnosis and an efficient treatment of FD, three different strategies of screening, new-born screening, high-risk screening and familiar screening, have been conducted. However, most of FD screening in the CKD population has been carried out in hemodialysis patients and kidney transplant recipients, for whom the renal damage is already irreversible, so the effectiveness of enzymatic replacement therapy is limited and delayed therapeutic intervention results in worse long-term outcomes. This review investigates the actual strategies of screening initiatives for the identification of FD, examining in detail those performed in CKD patients not on dialysis.

Muscle-tendon weakness contributes to chronic fatigue syndrome in Gaucher’s disease

Background Chronic fatigue (CFg) is a prevalent symptom in Gaucher disease (GD) at diagnosis (79%) and remains in a quarter of patients after years of therapy. Bone abnormalities are present in over 70% and peripheral neuropathy in about 11% of the patients, which contributes to the disabling and debilitating complications. Our hypothesis is that other factors such as muscle-tendinous weakness could have influence in the development of CFg. Methods We have evaluated the fiber structure and elasticity of muscle-tendinous unit by strain-elastography (S-ELA) and analyzed their influence in the CFg. S-ELA study was performed in Achilles tendon in 25 type 1 and two type 3 GD patients, all of them with fatigue and were on enzymatic replacement therapy for mean 13 years; simultaneously, bone marrow burden by MRI and calcaneus ultrasound densitometry were evaluated. Blood cell counts, plasma biomarkers, GBA1 genotyping, and SF36 quality of life scale (QoL) were also performed. Statistical analysis: descriptive and comparative test. Results All patients showed a normal Achilles tendinous structure. Abnormal stiff grade 2–3 was found in 17/27 (62.9%); in 11/27 (40.7%) of patients, the alteration was bilateral. There were no correlations between the S-ELA results to other variables; nevertheless, a significant correlation between the degree of tendon hardness and the low score on the QoL scales (p = 0.0035) was found. The S-ELA is a sensitive painless, fast, and low cost method to detect muscle-tendinous subclinical dysfunction that could contribute to CFg in GD. The identification of subclinical tendon alteration would be a sign of alarm, focused on the risk of development of bone complications. Conclusion Intratendinous alteration in strain-elastography is an independent variable in GD patients with persistent fatigue.

Case Report: Pancytopenia as an indicator for lysosomal storage disease (Gaucher's Disease)

Introduction: Lysosomal storage disorders are a rare group of diseases with genetic origin in which Gaucher Disease (GD) stands out as the most frequent. GD type 1 is the most common form of this condition, and patients with this pathology present with unexplained cytopenias, in addition to hepatosplenomegaly, bone involvement, and in other cases neurological disorders. A case of a patient is presented, whose results showed thrombocytopenia and leukopenia in addition to hepatosplenomegaly. In Latin America, there are very few reported cases of this clinical entity, and information on this disease is very limited. Case: We present a case of a patient diagnosed with GD, who presented with thrombocytopenia and leukopenia in addition to hepatosplenomegaly, with the aim of emphasizing the importance of early recognition of this pathology, especially in patients with unexplained cytopenia’s or hepatosplenomegaly’s. In suspicion of GD, enzymatic quantification of β-glucocerebrosidase was performed, showing its deficit in addition to alteration in the GBA gene. Unfortunately, enzymatic replacement could not be done because the Cerazyme (imiglucerase for injection) is not available in Ecuador. Nevertheless, the patient was treated with analgesic (1g of paracetamol generally three times a day) and vitamin supplements (Dayamineral). Currently the patient is waiting for transfer to a foreign institution; she continues with bicytopenia and hepatosplenomegaly, her conditions are expected to be remit once the enzymatic treatment has been administered. Conclusion: We believe that the timely recognition of this disease will allow the initiation of enzymatic replacement therapy in an effective manner, in order to reduce morbidity and improve the clinical aspects of the patient.