China
Africa
Explore chapters and articles related to this topic
Carrier Screening For Inherited Genetic Conditions
Published in Vincenzo Berghella, Obstetric Evidence Based Guidelines, 2022
Whitney Bender, Lorraine Dugoff
Clinical features: This disease is a lysosomal storage disorder caused by a deficiency of sphingomyelinase. Affected infants will appear normal at birth but develop hepatosplenomegaly, feeding difficulty, and motor regression within the first few months of life. Macular cherry red spots on fundoscopic exam can be seen in 50% of patients. Death typically occurs by 2–3 years of age.
Niemann-Pick disease
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
The molecular defect is in the enzyme sphingomyelinase (see Figure 91.2) [8, 9]. The enzyme was first purified from rat liver [57]. It cleaves the phosphocholine moiety from sphingomyelin. It is a lysosomal enzyme with a pH optimum about 4.5 and a molecular weight of approximately 70 kDa [58, 59]. The cDNA predicts a protein monomer of 64 kDa; if the six potential glycosylations were filled the molecular weight would be 72–74 kDa. There are a number of sphingomyelinase activator proteins (SAPs), but they do not appear to be required for enzymatic activity.
Metabolic, Degenerative, and Unclassified Conditions Associated With Interstitial Lung Disease
Published in Lourdes R. Laraya-Cuasay, Walter T. Hughes, Interstitial Lung Diseases in Children, 2019
In clinical types A and B, there is a clear deficiency of sphingomyelinase, an enzyme that hydrolyzes sphingomyelin to yield ceramide and phosphorylcholine. The most common disorder is type A, the infantile neuronopathic disorder which begins shortly after birth with hepatosplenomegaly, failure to thrive, and neurological impairment. Retinal cherry spots occur, but seizures and hypersplenism are rare. Ashkenazi Jews usually have type A.
Ocular Manifestations of Neuronal Ceroid Lipofuscinoses
Published in Seminars in Ophthalmology, 2021
Rohan Bir Singh, Prakash Gupta, Akash Kartik, Naba Farooqui, Sachi Singhal, Sukhman Shergill, Kanwar Partap Singh, Aniruddha Agarwal
Massive neuronal loss and accumulation of intracellular acidic sphingomyelinase are the predominant features in all patients. Moreover, genetic heterogeneity adds to this challenge. Urine sediment dolichol levels are elevated in both types – it’s a nonspecific but helpful finding. Neuroradiological findings in CLN-4 disease: include parieto-occipital cortical atrophy, cerebellar atrophy, hyperintense periventricular areas; and periventricular thinning and enlargement.98–100A cortical layer-specific loss of neurons has been described in layers 2 and 3 for CLN-4 disease, and EEG in the patients reveals a slow background, polyphasic spikes, and slow-wave changes.7,100,101 These changes can most reliably be confirmed by invasive brain biopsy.96 The diagnosis remains neuropathological, and despite the rarity of disease and absence of noninvasive diagnostic techniques, several criteria and guidelines are being developed by experts.89
Small extracellular vesicles (sEVs): discovery, functions, applications, detection methods and various engineered forms
Published in Expert Opinion on Biological Therapy, 2021
Manica Negahdaripour, Hajar Owji, Sedigheh Eskandari, Mozhdeh Zamani, Bahareh Vakili, Navid Nezafat
Lipids, including ceramide and phosphatidic acid (PA), can cause inward budding, and thus ILV formation and cargo sorting. Sphingomyelin is converted into ceramide by the activity of sphingomyelinase. Ceramide accumulates and causes lipid raft formation which leads to ILV sorting [44]. PA is produced out of phosphatidylcholine by phospholipase D2 (PLD2) and acts in the same manner as ceramide [45]. Tetraspanins, such as CD63, CD9, CD81, and TSPAN8, have demonstrated cargo sorting potential [46–48]. Interestingly, in this pathway also one of the sphingomyelin metabolites, called sphingosine-1-phosphate (SIP), plays a role. Silencing of the SIP receptors impaired the formation of CD63 and CD81, and thus protein sorting. Other transmembrane proteins such as flotillins have been also reported to be important in protein sorting and rely on the presence of SIP [49]. Another example of sorting which happens through the recruitment of both lipids and proteins is PMEL17. PMEL17 is a melanosomal protein, which engages its luminal domains with lipids to cause ILV sorting [50]. Finally, HSP70 was reported to be involved in cargo sorting through the recruitment of transferrin receptors or binding with the KFERQ-motif of cytosolic proteins [51].
Use of electron microscopy when screening liver biopsies from neonates and infants: experience from a single tertiary children’s hospital (1991-2017)
Published in Ultrastructural Pathology, 2020
Mikako Warren, Mai Shimura, Eric P. Wartchow, Shoji Yano
NPC is an autosomal recessive lysosomal storage disorder that affects multiple organs. NPC is divided into type A/B caused by SMPD1 gene mutations and type C caused by NPC1 or NPC2 mutations. In type A/B, acid sphingomyelinase activity is impaired and excess sphingomyelin accumulates in the hepatocytes and Kupffer cells. Patients with NPC commonly presented with prominent hepatosplenomegaly, which was also seen in Case 8. The diagnosis was confirmed by no activity in sphingomyelinase detected by biochemical testing (Table 3). Histologically, the liver shows a storage pattern of injury associated with enlarged hepatocytes and dilated sinusoid filled with “foamy” Kupffer cells. EM shows the accumulation of myelinosomes within the hepatocytes and Kupffer cells.