Unique case of 19p13 syndrome with storage pool disease

Introduction/Objective Microdeletion of a region of the short arm of chromosome 19 results in a very rare syndrome called 19p13.3 deletion syndrome, which manifest itself in developmental delay as well as structural abnormalities such as facial dysmorphism and macrocephaly. Methods/Case Report We present a case of 14-month-old patient, born at term and was large for her gestational age. She had dysmorphic facial features including posterior cleft palate for which, she required placement of G-tube. Post-delivery, she experienced respiratory distress as well as hypoglycemic episodes. Over the period of time, her mother also noticed occasional bleeding through her gums with teething. Genetic workup was performed, which revealed 2.4 Mb of microdeletion at chromosome 19 region p13.3, including deletion of PIAS4, MAP2K2, GNA11, TBXA2R, RAX2 genes. TBXA2R mutation is associated with bleeding disorder due to a defect in platelet aggregation. The mutation in TBXA2R can lead to platelet type 13 bleeding disorder. For this purpose, a platelet aggregation study was performed to evaluate platelet function disorders. However, the result of the platelet aggregation study was inconclusive as it showed decrease responses to all agonists including arachidonic acid, epinephrine, ADP, collagen and ristocetin. Further work-up by electron microscopy (EM) of platelets (PL) revealed a significant decrease of delta granules (DG) (0.89 DG/PL, normal 4-6 DG/PL), consistent with delta granule storage pool deficiency (δ-SPD). Other abnormalities observed by EM included occasional gray platelets, platelets with immature and/or decreased numbers of α-granules, and rare giant α-granules. Results (if a Case Study enter NA) NA Conclusion To the best of our knowledge, no other case of 19p13.3 microdeletion syndrome with δ-SPD and associated abnormalities in α-granules has previously been described in the literature. Although it is unclear if there is any relationship between δ-SPD and 19p13.3 deletion syndrome, further investigation is warranted.

Low Neonatal Circumcision Bleeding Rate in Patients Diagnosed with Delta-Storage Pool Deficiency Later in Life

Introduction male circumcision is a common procedure, generally performed during the newborn period. Few reports have described circumcision in patients with bleeding disorders. Aim to determine bleeding rate after circumcision in neonatal male subjects who were diagnosed later in life with delta-storage pool disease (SPD). Methods we retrospectively reviewed the medical records of male subjects (<18 years of age) who were diagnosed with SPD later in life and were circumcised at birth without hemostatic prophylaxis due to lack of family history at that time from 2000-2020. Intraoperative/postoperative bleeding and bleeding severity were the main outcomes evaluated. Results 153 male subjects were included. Circumcision was performed at a median age of 2 days (range, 1 day-4 months). The main indication for circumcision was parental request. Median severity of granule deficiency was 2.76 dense granules/platelet (range, 1.12-3.82 DG/Plt). None of the subjects had intraoperative bleeding. Three subjects (2%) had postoperative bleeding and only one (0.65%) required ER intervention to stop bleeding. Conclusion the overall incidence of bleeding in our subjects with SPD who were undiagnosed and untreated at circumcision, is comparable to that reported for patients without a bleeding disorder.

Platelet δ-Storage Pool Disease: An Update

Platelet dense-granules are small organelles specific to the platelet lineage that contain small molecules (calcium, adenyl nucleotides, serotonin) and are essential for the activation of blood platelets prior to their aggregation in the event of a vascular injury. Delta-storage pool diseases (δ-SPDs) are platelet pathologies leading to hemorrhagic syndromes of variable severity and related to a qualitative (content) or quantitative (numerical) deficiency in dense-granules. These pathologies appear in a syndromic or non-syndromic form. The syndromic forms (Chediak–Higashi disease, Hermansky–Pudlak syndromes), whose causative genes are known, associate immune deficiencies and/or oculocutaneous albinism with a platelet function disorder (PFD). The non-syndromic forms correspond to an isolated PFD, but the genes responsible for the pathology are not yet known. The diagnosis of these pathologies is complex and poorly standardized. It is based on orientation tests performed by light transmission aggregometry or flow cytometry, which are supplemented by complementary tests based on the quantification of platelet dense-granules by electron microscopy using the whole platelet mount technique and the direct determination of granule contents (ADP/ATP and serotonin). The objective of this review is to present the state of our knowledge concerning platelet dense-granules and the tools available for the diagnosis of different forms of δ-SPD.

Functional Classification of Paediatric Patients with Non-syndromic Delta-Storage Pool Deficiency

Storage pool disease (SPD) covers a group of platelet defects in which α- and/or delta-granules are reduced or cannot be secreted adequately in response to agonists. The detection of delta-granule release defects is hampered by a lack of fast and feasible tests. We aimed to implement a flow cytometry–based kinetic mepacrine assay to better identify and subgroup childhood patients with a mild to moderate bleeding diathesis and compare our method to established laboratory tests. We analysed 50 children with suspected SPD whose initial parameters were re-assessed in a second site visit. Mepacrine uptake and release patterns were correlated with CD63 exposure, platelet ADP/ATP release and content, and the bleeding score ascertained by the ISTH-BAT. Mepacrine release was overall significantly reduced in investigated patients compared with controls. Summarizing, our time-resolved approach proved to be a quick and inexpensive tool that was additionally able to distinguish between mepacrine uptake, mepacrine release, and combined defects. Classification of patients using such a kinetic assay makes it feasible to sensitively detect frequently missed SPD and to group these patients for further analyses and clinical correlations.