Main skin manifestations of COVID-19 have been recently classified. However, little is known about cutaneous histopathological patterns and the presence of SARS-CoV-2 in these skin lesions. We present a healthy 29-year-old man who developed a leucocytoclastic vasculitis for COVID-19 with positive SARS-CoV-2 PCR in skin biopsy.

Fabry disease (FD) is a lysosomal storage disorder caused by deficient alpha-galactosidase A activity in the lysosome due to mutations in the GLA gene, resulting in gradual accumulation of globotriaosylceramide and other derivatives in different tissues. Substrate accumulation promotes different pathogenic mechanisms in which several mediators could be implicated, inducing multiorgan lesions, mainly in the kidney, heart and nervous system, resulting in clinical manifestations of the disease. Enzyme replacement therapy was shown to delay disease progression, mainly if initiated early. However, a diagnosis in the early stages represents a clinical challenge, especially in patients with a non-classic phenotype, which prompts the search for biomarkers that help detect and predict the evolution of the disease. We have reviewed the mediators involved in different pathogenic mechanisms that were studied as potential biomarkers and can be easily incorporated into clinical practice. Some accumulation biomarkers seem to be useful to detect non-classic forms of the disease and could even improve diagnosis of female patients. The combination of such biomarkers with some response biomarkers, may be useful for early detection of organ injury. The incorporation of some biomarkers into clinical practice may increase the capacity of detection compared to that currently obtained with the established diagnostic markers and provide more information on the progression and prognosis of the disease.

In patients with Fabry disease (FD), treatment with enzyme replacement therapy (ERT), may trigger the formation of anti-drug antibodies (ADAs). The consequences of this immune reaction range from the transient appearance of clinically insignificant ADAs to the generation of neutralizing antibodies that negate the clinical benefit of the biotherapeutic agent, lead to side effects (such as injection site reactions), and even cause severe, life-threatening symptoms. Many factors may influence the immunogenicity of these therapeutic proteins. Currently, there are three commercially available long-term ERT treatments in patients with FD: agalsidase alfa, agalsidase beta, and more recently, pegunigalsidase alfa. Neutralizing ADAs are present in approximately 40% of male FD patients treated with ERT based on agalsidase alfa or agalsidase beta and have shown in vitro cross-reactivity with both agalsidases. Their formation seems to be irreversible, meaning that most patients with positive neutralizing ADAs remain so for up to 10 years after starting treatment. Recent studies show that in some patients, pre-existing ADAs against agalsidase alfa and agalsidase beta have lower affinity and lower inhibitory effects against pegunigalsidase alfa. Additionally, in clinical trials involving naïve patients, neutralizing antibodies were mostly transient, although further studies are needed to confirm these findings in clinical practice. The formation of ADAs is often associated with a worse clinical prognosis and a faster progression of the disease. Given the rapid progression of FD, measuring ADAs titers is essential to provide personalised treatment for each patient. This is why international recommendations highlight the importance of monitoring the existence of ADAs, their neutralising activity, and globotriaosylsphingosine (lyso-Gb3) levels in patients receiving ERT. However, several unresolved issues remain, such as the importance of ADAs levels (particularly neutralising ADAs), the standardisation of assay methods, the interpretation of results, and the implications of these findings for therapeutic strategies. Overcoming the development of ADAs is critical to improving treatment outcomes in patients with FD, different strategies have been explored to address this challenge. The present work aims to review latest developments related to all aspects mentioned above, while also analyzing the potential role of therapeutic innovations.

This was a retrospective, multicenter study that aimed to report the characteristics of type 3 Gaucher disease (GD3) patients in Spain, including the genotype, phenotype, therapeutic options, and treatment responses. A total of 19 patients with GD3 from 10 Spanish hospitals were enrolled in the study (14 men, 5 women). The median age at disease onset and diagnosis was 1 and 1.2 years, respectively, and the mean age at follow-up completion was 12.37 years (range: 1–25 years). Most patients exhibited splenomegaly (18/19) and hepatomegaly (17/19) at the time of diagnosis. The most frequent neurological abnormalities at onset were psychomotor retardation (14/19) and extrinsic muscle disorders (11/19), including oculomotor apraxia, supranuclear palsy, and strabismus. The L444P (c.1448T>C) allele was predominant, with the L444P (c.1448T>C) homozygous genotype mainly associated with visceral manifestations like hepatosplenomegaly, anemia, and thrombocytopenia. All patients received enzyme replacement therapy (ERT); other treatments included miglustat and the chaperone (ambroxol). Visceral manifestations, including hepatosplenomegaly and hematological and bone manifestations, were mostly controlled with ERT, except for kyphosis. The data from this study may help to increase the evidence base on this rare disease and contribute to improving the clinical management of GD3 patients.

Background/Objectives: The present study updates the Spanish registry of patients with urea cycle disorders (UCD), originally established in 2013, to provide comprehensive epidemiological data and evaluate the impact of therapeutic strategies and newborn screening (NBS) on clinical outcomes. Methods: This retrospective, multicenter study focuses on 255 Spanish UCD patients. It includes all living and deceased cases up to February 2024, analyzing demographic, clinical, and biochemical variables. Results: The incidence of UCD in Spain over the past decade was 1:36,063 births. The most common defects were ornithine transcarbamylase deficiency (OTCD) and argininosuccinate synthetase deficiency. Early-onset (EO) cases comprised 32.7%, and 10.6% were diagnosed through NBS. Global mortality was 14.9%, higher in carbamoylphosphate synthetase 1 deficiency (36.8%) and male OTCD patients (32.1%) compared to other defects (p = 0.013). EO cases presented a higher mortality rate (35.8%) than late-onset (LO) cases (7.1%) (p < 0.0001). The median ammonia level in deceased patients was higher at 1058 µmol/L (IQR 410–1793) than in survivors at 294 µmol/L (IQR 71–494) (p < 0.0001). Diagnosis through NBS improved survival and reduced neurological impairment compared to symptomatic diagnosis. Neurological impairment occurred in 44% of patients, with worse neurological outcomes observed in patients with argininosuccinate lyase deficiency, arginase 1 deficiency, hyperornithinemia-hyperammonemia-homocitrullinuria, EO presentations, pre-2014 diagnosis, and patients with higher levels of ammonia at diagnosis. Among transplanted patients (20.6%), survival was 95.2%, with no significant neurological differences compared to non-transplanted patients. Conclusions: This updated analysis highlights the positive impact of NBS and advanced treatments on mortality and neurologic outcomes. Persistent neurological challenges underscore the need for further therapeutic strategies.