Novel G377S (c.1246G>T) mutation associated with Gaucher disease type 1

Abstract

To the editor: My father, Kenneth M. Moser, MD, was a pioneer in pulmonary medicine. His passion and best known work was in pulmonary vascular diseases, but he also underlined the importance of invasive diagnostics in approaching acute diffuse pulmonary infiltrates [1]. After spending decades hearing about his efforts to save the lives of those suffering from pulmonary diseases, it never occurred to me that I would almost die from a serious respiratory illness.Diagnosed with myelofibrosis in 2009, my body has been afflicted by all the attendant symptoms including anemia, thrombocytopenia, splenomegaly, hepatomegaly, rashes, night sweats, bone pain, and extramedullary hematopoiesis (EMH) [2]. In the attentive care of my doctor and his team at the Mayo Clinic, my course of treatment had been fairly straightforward. As my disease became more aggressive, routine surveillance was supplanted by the use of experimental drugs. It was not until I developed acute respiratory distress syndrome (ARDS) in January 2013 that the direction my treatment should take became unclear.I was already in the hospital regaining strength from a challenging series of surgeries to evacuate a spontaneous retroperitoneal hematoma when my oxygen saturation level began to plummet. Despite never needing oxygen before, within a matter of days, I needed 4 L of oxygen to maintain saturation in the mid-90s. I was moved to the intensive care unit and given nebulizer treatments with little effect. The regular nasal cannula was soon replaced by a humidified high pressure nasal cannula which quickly gave way to a continuous positive airway pressure. On chest films, pleural effusion, atelectasis, and infiltrates consistent with pneumonia were detected. I received high doses of antibiotics and prednisone, however, my condition continued to deteriorate. A subsequent bronchoscopy revealed diffuse alveolar hemorrhage. I was put on a ventilator. As Friday evening set in, an array of determined Mayo Clinic doctors from multiple disciplines convened to solve the riddle of the source of my ARDS and develop a treatment strategy.My hematologist hypothesized that pulmonary EMH was responsible for my acute deterioration, a rare and infrequently reported complication of advanced myelofibrosis, however, to him the most parsimonious explanation for the ARDS [3]. He advocated for a bone marrow scan that confirmed the suspected diagnosis and 2 hours after the bone marrow scan, I received a 100-cGy dose of radiation to my lungs [4]. On Tuesday morning, four days after the radiation, my lungs had cleared enough to take me off the ventilator. Later that afternoon, I was sitting in a chair, relishing several cups of sherbet. The next day, I took a walker assisted stroll around the unit. Two days after being extubated, I was moved from to a general floor where my recovery progressed at a steady pace. It has been three months since that single dose of radiation to my lungs saved my life. I am home now, I have a good quality of life and with my doctor's help, I will do my best t...

Three mutations of adult type 1 Gaucher disease found in a Chinese patient

“…[10] In our present study, we reviewed the new mutations reported from 2008 to 2018 (Table 1). [2,7,9–21] As shown in Table 1, more mutations were identified in type 1 GD than type 2 and 3 GD in recent years. The mutation spectrum of GBA in Chinese patients was quite different from those seen in Jewish and non-Jewish Caucasian patients.…”

Premature Identical Twin Neonates With Sleep Apnea

“…A substitution of glycine for serine in the same codon (p.Gly377Ser) was previously described in patients with GD-1 and GD-2 of Portuguese and Spanish ancestry. [9][10][11] The p.Gly377Cys results in a disruptive amino acid substitution from a small and nonpolar amino acid (glycine, Gly) to a sulfur-containing amino acid (cysteine, Cys). This results in lower GCase enzymatic activity in comparison with other mutants (Figure 1), predicting an earlier onset and rapidly progressive clinical course as observed in the twins reported here.…”