Lysosomal storage disorders

Xing M, Parker EI, Moreno-De-Luca A, Harmouche E, Terk MR. Radiological and clinical characterization of the lysosomal storage disorders: non-lipid disorders. Br J Radiol. 2014 Jan;87(1033):20130467.

“Lysosomal storage diseases (LSDs) are a large group of genetic metabolic disorders that result in the accumulation of abnormal material, such as mucopolysaccharides, glycoproteins, amino acids and lipids, within cells. Since many LSDs manifest during infancy or early childhood, with potentially devastating consequences if left untreated, timely identification is imperative to prevent irreversible damage and early death. In this review, the key imaging features of the non-lipid or extralipid LSDs are examined and correlated with salient clinical manifestations and genetic information. Disorders are stratified based on the type of excess material causing tissue or organ dysfunction, with descriptions of the mucopolysaccharidoses, mucolipidoses, alpha-mannosidosis, glycogen storage disorder II and cystinosis. In addition, similarities and differences in radiological findings between each of these LSDs are highlighted to facilitate further recognition. Given the rare and extensive nature of the LSDs, mastery of their multiple clinical and radiological traits may seem challenging. However, an understanding of the distinguishing imaging characteristics of LSDs and their clinical correlates may allow radiologists to play a key role in the early diagnosis of these progressive and potentially fatal disorders.”

Children’s and Emory users, contact Emily Lawson for full-text. 

Klein AD, Futerman AH. Lysosomal storage disorders: old diseases, present and future challenges. Pediatr Endocrinol Rev. 2013 Nov;11 Suppl 1:59-63.

“Lysosomal storage diseases (LSDs), which are inborn errors of metabolism, encompass around 50 different inherited syndromes. Together, they have an incidence of 1/7000 newborns. LSDs are caused by deficiencies in lysosomal enzymes or transporters, resulting in intra-lysosomal buildup of under graded metabolites. Common features of LSDs include bone disease, organomegaly and central and peripheral nervous system degeneration. These diseases were first described in the 1880s. Despite more than a hundred years of study of the genetic and molecular bases of LSDs, little is known about the events that lead from intra-lysosomal accumulation to the distinctive cell dysfunction and pathology that is characteristic of each disease. This review focuses on the main historical discoveries in LSD biology, from the original descriptions of their phenotypes, to animal models, including therapeutic strategies and challenges to treat this family of devastating diseases.”

Children’s and Emory users, contact Emily Lawson for full-text. 

Boustany RM. Lysosomal storage diseases–the horizon expands. Nat Rev Neurol. 2013 Oct;9(10):583-98.

“Since the discovery of the lysosome in 1955, advances have been made in understanding the key roles and functions of this organelle. The concept of lysosomal storage diseases (LSDs)–disorders characterized by aberrant, excessive storage of cellular material in lysosomes–developed following the discovery of α-glucosidase deficiency as the cause of Pompe disease in 1963. Great strides have since been made in understanding the pathobiology of LSDs and the neuronal ceroid lipofuscinoses (NCLs). The NCLs are neurodegenerative disorders that display symptoms of cognitive and motor decline, seizures, blindness, early death, and accumulation of lipofuscin in various cell types, and also show some similarities to ‘classic’ LSDs. Defective lysosomal storage can occur in many cell types, but the CNS and PNS are particularly vulnerable to LSDs and NCLs, being affected in two-thirds of these disorders. Most LSDs are inherited in an autosomal recessive manner, with the exception of X-linked Hunter disease, Fabry disease and Danon disease, and a variant type of adult NCL (Kuf disease). This Review provides a summary of known LSDs, and the pathways affected in these disorders. Existing therapies and barriers to development of novel and improved treatments for LSDs and NCLs are also discussed.”

Full-text for Emory users.

Staretz-Chacham O, Lang TC, LaMarca ME, Krasnewich D, Sidransky E. Lysosomal storage disorders in the newborn. Pediatrics. 2009 Apr;123(4):1191-207.

“Lysosomal storage disorders are rare inborn errors of metabolism, with a combined incidence of 1 in 1500 to 7000 live births. These relatively rare disorders are seldom considered when evaluating a sick newborn. A significant number of the >50 different lysosomal storage disorders, however, do manifest in the neonatal period and should be part of the differential diagnosis of several perinatal phenotypes. We review the earliest clinical features, diagnostic tests, and treatment options for lysosomal storage disorders that can present in the newborn. Although many of the lysosomal storage disorders are characterized by a range in phenotypes, the focus of this review is on the specific symptoms and clinical findings that present in the perinatal period, including neurologic, respiratory, endocrine, and cardiovascular manifestations, dysmorphic features, hepatosplenomegaly, skin or ocular involvement, and hydrops fetalis/congenital ascites. A greater awareness of these features may help to reduce misdiagnosis and promote the early detection of lysosomal storage disorders. Implementing therapy at the earliest stage possible is crucial for several of the lysosomal storage disorders; hence, an early appreciation of these disorders by physicians who treat newborns is essential.”

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Fletcher JM. Screening for lysosomal storage disorders–a clinical perspective. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):405-8.

“The availability of therapies for lysosomal storage diseases (LSDs) and clear documentation from animal studies that optimal therapy depends on early diagnosis have set the scene for newborn screening for LSDs. The combined incidence of this group of conditions is approximately 1 in 7000, well within the feasible range for newborn screening programmes. The availability of multiplex technology has facilitated the technical aspects of initial screening. The scientific challenge is to predict disease severity early enough to influence choice of therapy. LSD screening is discussed from the point of view of the scientists, the families affected by these conditions, the community and clinicians.”

Full-text for Emory users.

More PubMed results on LSDs.

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