Lysosomal storage diseases (LSD) include a wide range of different disorders with variable degrees of respiratory system involvement. The purpose of this narrative review is to treat the different types of respiratory manifestations in LSD, with particular attention being paid to the main molecular pathways known so far to be involved in the pathogenesis of the disease. A literature search was conducted using the Medline/PubMed and EMBASE databases to identify studies, from 1968 through to November 2018, that investigated the respiratory manifestations and molecular pathways affected in LSD. Pulmonary involvement includes interstitial lung disease in Gaucher’s disease and Niemann-Pick disease, obstructive airway disease in Fabry disease and ventilatory disorders with chronic respiratory failure in Pompe disease due to diaphragmatic and abdominal wall muscle weakness. In mucopolysaccharidosis and mucolipidoses, respiratory symptoms usually manifest early in life and are secondary to anatomical malformations, particularly of the trachea and chest wall, and to accumulation of glycosaminoglycans in the upper and lower airways, causing, for example, obstructive sleep apnea syndrome. Although the molecular pathways involved vary, ranging from lipid to glycogen and glycosaminoglycans accumulation, some clinical manifestations and therapeutic approaches are common among diseases, suggesting that lysosomal storage and subsequent cellular toxicity are the common endpoints.

Objectives Fabry disease (FD) is an X-linked lysosomal storage disorder, resulting from a deficiency of the enzyme α-galactosidase A, responsible for breaking down glycolipids such as globotriaosylceramide and its deacylated derivative, globotriaosylsphingosine (LysoGb3). Here, we compare the levels of LysoGb3 in dried blood spots (DBS) and plasma in patients with classic and late-onset phenotypes. Methods LysoGb3 measurements were performed in 104 FD patients, 39 males and 65 females. Venous blood was collected. A portion was spotted onto filter paper and another portion separated to obtain plasma. The LysoGb3 concentrations in DBS and plasma were determined by highly sensitive electrospray ionization liquid chromatography tandem mass spectrometry. Agreement between different matrices was assessed using linear regression and Bland Altman analysis. Results The method on DBS was validated by evaluating its precision, accuracy, matrix effect, recovery, and stability. The analytical performances were verified by comparison of a total of 104 paired DBS and plasma samples from as many FD patients (representing 46 GLA variants). There was a strong correlation between plasma and the corresponding DBS LysoGb3 concentrations, with few exceptions. Discrepancies were observed in anemic patients with typically low hematocrit levels compared to the normal range. Conclusions The method proved to be efficient for the rapid analysis of LysoGb3. DBS provides a convenient, sensitive, and reproducible method for measuring LysoGb3 levels for diagnosis, initial phenotypic assignment, and therapeutic monitoring in patients with FD.

Background The treatment with recombinant human growth hormone in patients affected by Mucopolysaccharidoses (MPS) is considered whenever a concurrent diagnosis of growth hormone deficiency is demonstrated. The short- and long-term effects of recombinant human growth hormone in this selected cohort is still debated, given the natural progression of disease-related skeletal malformations and the paucity of treated patients reported in literature. The presented case series provides detailed information about the response to recombinant growth hormone in MPS patients diagnosed with growth hormone deficiency. Cases presentation The growth patterns of 4 MPS female patients (current age: 11.7–14.3 years) treated with recombinant human growth hormone due to growth hormone deficiency have been retrospectively analyzed. Two patients, diagnosed with MPS IH, had undergone haematopoietic stem cell transplantation at an early age; the remaining two patients were affected by MPS IV and VI and were treated with enzyme replacement therapy. 4/4 patients presented with a progressive growth deceleration before the diagnosis of growth hormone deficiency was confirmed. This trend was initially reverted by a remarkable increase in height velocity after the start of recombinant growth hormone. We recorded an average increase in height velocity z-score of + 4.23 ± 2.9 and + 4.55 ± 0.96 respectively after 6 and 12 months of treatment. After the first 12–24 months, growth showed a deceleration in all the patients. While in a girl with MPS IH recombinant human growth hormone was discontinued due to a lack in clinical efficacy, 3/4 patients grew at a stable pace, tracking the height centile achieved after the cited initial increase in height velocity. Furthermore, mineral bone density assessed via bone densitometry, showed a remarkable increase in the two patients who were tested before and after starting treatment. Conclusions Recombinant human growth hormone appears to have effectively reverted the growth deceleration experienced by MPS patients diagnosed with growth hormone deficiency, at least during the first 12–24 months of treatment.

We report the case of a 17-year-old boy with a mosaic trisomy 18, who was diagnosed with Hodgkin lymphoma. The patient showed only poor growth and two muscular ventricular septal defects; no facial dysmorphims were present. He was admitted to our hospital because of asthenia and weight loss; a mediastinal enlargement was found and an histological diagnosis of nodular sclerosis Hodgkin lymphoma on mediastinal biopsy was performed. Contextually, a chromosomal analysis on bone marrow aspirate and on peripheral blood revealed a mosaic trisomy 18. This result was confirmed also with cytogenetic analysis on skin fibroblasts. While there is a well-documented association between trisomy 18 and solid cell tumors, this is, to our knowledge, the first reported case of Hodgkin lymphoma in a patient with a mosaic trisomy 18, enlarging the spectrum of possible oncologic manifestations of the disease.

We describe a monochorionic diamniotic twin pregnancy in a 28-year-old woman with a severe form of sickle cell disease periodically treated with erythrocytapheresis (EA). During this high risk pregnancy, two sessions of EA were performed without complications, and pain control and fetal growth were optimal. Delivery was carried out by emergency cesarean section at 29(+3) weeks' gestation due to initial fetal distress following twin-to-twin transfusion. There were no significant complications for the newborn twins and the post-partum course was regular. The patient underwent a further EA 7 weeks after surgery. Close collaboration between obstetricians and hematologists with careful maternal-fetal monitoring and prophylactic EA during pregnancy led to a favorable outcome despite a low maternal body weight, a twin pregnancy, and a severe form of sickle cell disease.