Danon disease previously known as gsd iib, or pseudo pompe disease with normal gaa activity is an xlinked recessive lysosomal glycogen storage disease caused by mutations in the lysosomalassociated membrane protein 2 or lamp2 gene omim 309060 located at chromosomal position xq24. Danon disease medigoo health tests and free medical. Danon disease is an xlinked recessive lysosomal glycogen storage disease with normal acid maltase caused by mutations in the lysosomalassociated membrane protein 2 or lamp2 gene nishino et al. Characterisation of lamp2deficient rats for potential new. Dec 11, 2018 heart transplantation is the only curative treatment at this moment for the fatal cardiac component of danon disease. In males the symptoms of danon disease are more severe.
Pathology of infectious diseases, volume 1 volumes 12 of diagnostic pathology of infectious diseases pathology of infectious diseases, daniel h. Danon disease is a condition characterized by weakening of the heart muscle cardiomyopathy. Multimodality imaging of danon disease in a patient with a. The normal xchromosome protects females and explains, in part, the less severe symptoms and the delay in onset of symptoms until adulthood. To clarify the clinicopathological features and management, we performed the first nationwide, questionnairebased survey on danon disease in japan. Fulltext pdf cardiac cycle time intervals are back again1. Danon disease is an xlinked dominant skeletal and cardiac muscle disorder with multisystem clinical manifestations. He is also possibly the longestknown survivor of this disease without a heart. Weakness involving the upper legs is typically noticed first, affecting activities such as running and climbing stairs.
Danon disease presenting as severe myocardial hypertrophy. The diagnostic features of these disorders on endomyocardial biopsy will be discussed along with the impact of endomyocardial biopsybased diagnoses on patient. In danon disease, however, although hcm is a major feature, other organ systems are also involved. Danon disease mutation and one normal xchromosome where the lamp2 gene is functioning normally. Lysosomes are particles found in cells, they contain enzymes that break down substances within the cell. Lysosomal palmitoylprotein thioesterase ppt, grods, saposins a and d. While the exact danon disease prevalence is not known, it is a very rare condition, and as a consequence, not many doctors are aware of its diagnosis. Feb 09, 2016 in danon disease, however, although hcm is a major feature, other organ systems are also involved. Males with danon disease usually develop the condition earlier than females and are more severely affected.
For example, the buildup of glycogen in the lysosomes of muscle in danon disease originally led to its classification as a variant of gsd type ii danon et al. Danon disease looked initially like another rare genetic condition called pompe disease. The epub format uses ebook readers, which have several ease of reading features already built in. Danon disease is caused by a change mutation in a gene called lamp2. The nature of disease pathology for health professions by thomas h. Danon disease is a rare genetic disorder of which males are more severely affected than females. Danon disease is more common in males, and symptoms begin in early childhood or adolescence. Mutations that lead to a complete absence of the lamp2 protein have been shown to be most detrimental in terms of prognosis. Ijms free fulltext a nationwide survey on danon disease. Here we describe the importance of multimodality imaging of danon disease in a patient with a novel lamp2.
Males usually present with childhood onset concentric hypertrophic cardiomyopathy that is progressive and often requires heart transplantation. What is striking here is that god said this to a people of the old covenant. Hello amazon customer service, i received the delivery of my order walkers pediatric gastrointestinal disease. Diagnostic pathology of infectious disease presents a comprehensive, organbased approach to the effective and accurate diagnosis of infectious diseases. However, some women with danon disease have progressed to the point of needing a heart transplant. In patients with danon disease, the basic biological process of removing and recycling dysfunctional cellular machinery doesnt work properly. Danon disease or glycogen storage disease due to lamp2 deficiency or lysosomal glycogen. Biochemical and clinical aspects of glycogen storage diseases. Other clinical manifestations include skeletal myopathy, cognitive defects and visual problems. Danon disease is a genetic deficiency in lysosomeassociated membrane protein 2 lamp2, a highly glycosylated constituent of the lysosomal membrane and characterized by a cardiomyopathy, skeletal muscle myopathy, and cognitive impairment. Feb 09, 2016 detection of somatic and germline mosaicism for the lamp2 gene mutation c.
Retinopathy in danon disease genetics and genomics. An unusual presentation of autism prinyarat burusnukul, md, emily c. Unfortunately, there is no causal therapy for danon s disease. In many cases, the condition is inherited by a parent, typically the mother. Danon disease is a rare genetic condition characterized by weakening of the heart muscle cardiomyopathy, weakening of the muscles used for movement skeletal muscles myopathy, and intellectual disability. The disorders of ketogenesis cause hypoglycemia and encephalopathy.
Dec 19, 2016 iyers son, suraj, was diagnosed with danon disease when he was 7 years old. Clinical hallmarks are a severe cardiomyopathy, muscle weakness, and mild. Lamp2 microdeletions in patients with danon disease circulation. The characteristics of danon s disease include childhood onset, male predominance, hypertrophic cardiomyopathy, mild myopathy, and mental retardation. In males, mean disease onset is in their early teens and in females in their late twenties.
Xlinked myopathy with excessive autophagy xmea is a type of inherited myopathy muscle disease that mainly affects males. Danon disease results from mutations in the lysosomeassociated membrane protein2 lamp2gene. It can be mistaken for other forms of heart disease andor muscular dystrophies, including pompe disease. This condition is an x linked condition and is so rare that the exact prevalence is unknown. Danon disease genetic and rare diseases information. Although individuals with danon disease have been clinically described since the early 1980s, the underlying molecular mechanisms involved in. Danon disease due to a novel lamp2 microduplication.
Jul 12, 2016 danon disease is a rare genetic condition characterized by weakening of the heart muscle cardiomyopathy, weakening of the muscles used for movement skeletal muscles myopathy, and intellectual disability. Danon disease nord national organization for rare disorders. Danon who together with colleagues originally described it 1981 as lysosomal glycogen storage disease with normal acid maltase. Danon disease is an xlinked dominant disorder characterized by intracytoplasmic vacuoles containing autophagic material and glycogen in cardiac and skeletal muscle cells, cardiomyopathy, and skeletal myopathy, with or without conduction defect, wolfparkinsonwhite wpw syndrome, or mental retardation 68. Iyers son, suraj, was diagnosed with danon disease when he was 7 years old. Muscle pathology of a male patient with danon disease.
Detection of somatic and germline mosaicism for the lamp2 gene mutation c. A total of 39 patients 17 males, 22 females from 20 families were identified in the analysis. The lamp2 gene provides instructions for making a protein called lysosomal associated membrane protein2 lamp2, which, as its name suggests, is found in the membrane of cellular structures called lysosomes. Danon disease is not usually evident at birth unless blood tests are done in a suspected case i. Lysosomes are compartments in the cell that digest and recycle materials. Danon disease is caused by mutations in the lamp2 gene. The initial episode usually occurs in the newborn period or early childhood during an infection with vomiting. The role the lamp2 protein plays in the lysosome is unclear. Ijms free fulltext a nationwide survey on danon disease in.
Autophagy dysregulation in danon disease cell death. Pathology and pathophysiology correlations, 9th edition. Decompensation leads to severe ketoacidosis in defects of ketone body utilization including mct1 transporter deficiency. Most danon disease mutations lead to an absence of lamp2 protein. The cardiac phenotype of danon disease is severe with early onset and poor prognosis, even in some manifesting female carriers. Danon disease genetic and rare diseases information center. Enable javascript to view the expandcollapse boxes. In a study of 20 male patients, the mean age at onset was 17 years range, 10 months to 19 years, and all patients except 1 died before the age of 30 years. As the disease progresses, the only remaining therapeutic option is. The lamp2 gene provides instructions for making a protein called lysosomal associated membrane protein2 lamp2, and is found in the membrane of cellular structures of the lysosomes. Diagnostic biopsies of the native heart sciencedirect. Differential diagnosis glycogenosis type ii pompe disease danon disease differs from juvenile or adult forms of glycogenosis type ii by the. Save up to 80% by choosing the etextbook option for isbn.
Lymphoma in danon disease with chronic rhabdomyolysis. Identification of novel therapeutics for danon disease. It is characterized by muscle weakness that begins in childhood that slowly worsens over time. Xlinked myopathy with excessive autophagy rare disease. The cardinal features of this condition are hypertrophic cardiomyopathy, preexcitation and tachyarrhythmias, and skeletal myopathy, with some affected persons manifesting intellectual disability andor pigmentary retinopathy. Most affected persons exhibit private point mutations. Disorders of ketogenesis and ketolysis oxford medicine. Danon disease is caused by a genetic defect mutation in a gene called lamp2 lysosomalassociated membrane protein 2. Jan 15, 2015 danon disease is an xlinked disorder clinically characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. Vockley, in cardioskeletal myopathies in children and young adults, 2017. The distinction between these two disorders is important because danon disease has a more rapid disease progression and higher mortality.
Danon disease caused by two novel mutations of the lamp2 gene. Part of the highly regarded diagnostic pathology series, this updated volume by drs. A novel lamp2 mutation associated with severe cardiac. Danon the disease reliablerxpharmacy blog, health blog.
In females the symptoms of danon disease are less severe. Danon disease dd is a rare xlinked autophagic vacuolar myopathy, characterized by high penetrance and severe cardiomyopathy. Nov, 20 danon disease is a rare xlinked disorder comprising hypertrophic cardiomyopathy, skeletal myopathy, intellectual disability, and retinopathy. Tiny autophagic vacuoles look like solid basophilic granules in muscle fibers with. Males are typically more severely affected than females. Download undergraduate biological sciences courses pdf.
Lamp2 is also known to promote autophagic flux and samples from patients of danon disease present accumulated lc3 positive autophagosomes and undigested lipofuscin, indicating defective autophagic. Danon disease previously known as gsd iib, or pseudo pompe disease with normal gaa activity is an xlinked recessive lysosomal glycogen storage disease caused by mutations in the lysosomalassociated membrane protein 2 or lamp2 gene omim 309060 located at chromosomal. Pathogenesis of sle and critically analyse the contribution of genetics. Danon disease is an inherited disorder of autophagy. Concise, focused chapters, supported by tables, diagrams, radiographs, and photographs, provide essential information to keep you up to date with new cardiac devices, the. All they had was a relationship with jehovah, yet this was enough to immunize them, and make them diseasefree. Danon disease is a multisystem condition with predominant involvement of the heart, skeletal muscles, and retina, with overlying cognitive dysfunction. To date, there are over 160 different mutations in the lamp2 gene identified in case reports and databases that could lead to danon disease. Danon disease or glycogen storage disease type iib is a metabolic disorder. Danon disease as an underrecognized cause of hypertrophic. A critical evaluation of liver pathology in humans with. Danon disease is an xlinked dominant disorder predominantly affecting cardiac muscle. Such disorders include amyloidosis, myocarditis, sarcoidosis, iron overload, glycogen storage disorders, and lysosomal storage disorders. Punctuated by humor, unique case studies that link pathology to realworld clinical applications, and absorbing tales from the history of medicine, this engaging book focuses on the patient as it guides you through the causes and consequences of common diseases.
The underlying defect is poorly understood, but is associated with a mutation in the lysosomeassociated membrane protein2 lamp2 gene and modulations in autophagy. Danon disease is a rare xlinked lysosomal storage disease lsd characterized by an early onset of muscle weakness and severe cardiomyopathy sometimes, necessitating heart transplantation. The cure for all diseases with many case histories of diabetes, high blood pressure, seizures, chronic fatigue syndrome, migraines, alzheimers, parkinsons, multiple sclerosis, and others showing that all of these can be simply investigated and cured. Danon disease has been referred to as glycogen storage disease iib gsdiib, but. Researchers identify new way to treat danon disease using. Recently we used a new technology to turn skin cells from two patients with this disease into stem cells.
The explanted heart of the proband of hcm3873 had fibrosis beneath the epicardium in the posterior left ventricle. It is characterized clinically by cardiomyopathy, myopathy, and mental retardation in boys. Danon disease dd is a rare, xlinked autophagic vacuolar myopathy. A novel lamp2 mutation associated with severe cardiac hypertrophy and microvascular remodeling in a female with danon disease. Danon disease is commonly mistaken for sarcomeric hcm, despite being a lysosomal storage disease. Due to its rarity, clinical presentation and outcomes are still uncertain.
Genedx 207 perry parkway gaithersburg, md 20877 toll free. The number of patients with danon disease in the united states is estimated to be less than 500. Pathology, diagnosis, management, but its not the complete set. Also called lysosome associated membrane protein 2 lamp2 x linked major constituent of lysosomal membranes also lamp1 functions. Danon disease, like pompe disease, is a muscle disorder caused by a primary defect in lysosomal proteins. Danon disease, an xlinked dominant cardioskeletal myopathy, is caused by primary deficiency of lysosomeassociated membrane protein2 lamp2. Endomyocardial biopsy in the nontransplant setting can be diagnostic for particular diseases. Danon disease life expectancy in men is 19 years, while females affected with this disease can live up to the age of 34 years. Among boys, the key features are diseased heart muscle cardiomyopathy, weakness of the body muscles skeletal myopathy and intellectual disability ranging from mild learning problems to mental retardation. Danon disease some disorders exhibiting abnormal glycogen accumulation can be classified as a gsd or otherwise, depending on the focus of the information. Danon disease is a rare, severe xlinked form of cardiomyopathy caused by deficiency of lysosomeassociated membrane protein 2 lamp2. Revelo is an ideal pointofcare reference for the accurate diagnosis of complex cardiovascular specimens. Danon disease is an xlinked lysosomal and glycogen storage disorder associated with hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability.
Danon disease is an xlinked dominant skeletal and cardiac muscle disorder with. Pathology for the health professions 2nd edition by mcconnell, thomas h. Patients, however, often manifest hepatic abnormalities, but liver function has not been well evaluated and the syndrome is relatively. World map of danon disease find people with danon disease through the map. It was first described in boys presenting with cardiomyopathy, skeletal myopathy, and varying degrees of intellectual disability. This case concerns a 30yearold male of danon disease presenting with symptoms and signs of systolic heart failure. Cardiomyopathy is a severe and lifethreatening problem, for which cardiac transplantation is the only therapeutic option. Mutations cause danon disease, a lysosomal glycogen storage disease with cardiomyopathy in adult women and men before age 20 years n engl j med 2005. Disorders of ketone body metabolism are characterized by episodes of metabolic decompensation.
The most striking finding in muscle biopsy samples is small basophilic granules scattered in myofibers, which are in fact. Background danon disease is an xlinked dominant disorder characterized by the clinical. Danon disease is rare and unfamiliar to most physicians. Danon disease is an xlinked disorder clinically characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. To assess the frequency of danon disease in children with hcm, yang et al. They concluded that danon disease may be underdiagnosed in the pediatric cardiology population.
Identification of novel therapeutics for danon disease using. Kradin covers the latest information on h1n1, as well as the use of immunohistochemical stains, pcr, immunoperoxidase, and other molecular techniques for a current. The first description of danon disease was in 1981 when 2 boys with heart and skeletal muscle disease muscle weakness and mental retardation were described. As our title emphasizes we have created a concise overview of this important field that will allow the busy physician, medical student, nurse practioner, and physician assistant to understand, diagnose and treat common.
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