Presentation
Abstract Neutral lipid storage disease with myopathy (NLSDM) presents with skeletal muscle myopathy and severe dilated cardiomyopathy in nearly 40% of cases. [ncbi.nlm.nih.gov]
Summary Clinical description Clinical presentation is extremely heterogeneous and involves the liver or the neuromuscular system. [orpha.net]
Treatment Options for Lysosomal Storage Disorders At present, there are no known cures for lysosomal storage disorders. [biomarin.com]
She presented to us with a history of several days of polyuria, polydipsia, and loss of weight. [casesjournal.biomedcentral.com]
Entire Body System
- Pain
The second brother, from the age of 44, had exercise intolerance, cramps and pain in lower limbs. He is currently 50 years old and has an asymmetric distal amyotrophy. [ncbi.nlm.nih.gov]
This form is characterized by muscle pain and cramps, often following moderate exercise; strenuous exercise can lead to nausea and vomiting. During exercise, muscle tissue can be abnormally broken down, releasing a protein called myoglobin. [ghr.nlm.nih.gov]
Definition A metabolic disorder characterized by myoglobinuria, increased serum creatine kinase levels, decreased phosphoglycerate mutase activity, myalgia, muscle pain, muscle cramps, exercise intolerance. [uniprot.org]
In general, symptoms include: Anemia (low red blood cell count) Enlarged spleen and liver Easy bleeding and bruising Tiredness Bone pain and fractures Joint pain Eye problems Seizures Krabbe disease: This affects the nervous system. [webmd.com]
- Gaucher Disease
Some of the most common lysosomal storage disorders include: Gaucher disease: Gaucher disease often causes spleen and liver enlargement, blood problems and bone issues. Learn more about Gaucher disease. [gaucherdisease.org]
Clinical features Vary according to the exact subtype of Gaucher disease Type I: non-neuronopathic Gaucher disease Type II: acute neuronopathic Gaucher disease Type III: chronic neuronopathic Gaucher disease All types Hepatosplenomegaly Bone: bone crises [amboss.com]
Gaucher Disease Types I, II, and III: Gaucher disease is the most common type of lysosomal storage disorder. [rarediseases.org]
- Anemia
These included coarse face, dysostosis multiplex, respiratory difficulty, proteinuria with glomerular foamy cells, neurological involvement with developmental delays, pyramidal signs, and severe chronic anemia. [ncbi.nlm.nih.gov]
The hemolytic form of GSDVII is characterized by hemolytic anemia, in which red blood cells are broken down (undergo hemolysis) prematurely, causing a shortage of red blood cells (anemia). [ghr.nlm.nih.gov]
Type VIII Muscle weakness Anemia Increased levels of uric acid Glycogen Storage Disease Diagnosis Glycogen storage disease diagnosis usually occurs in infancy or childhood as a result of the above symptoms. [chp.edu]
Results: For patients with GSD-Ia, problems included short stature (90%), hepatomegaly (100%), hepatic adenomas (75%), anemia (81%), proteinuria or microalbuminuria (67%), kidney calcifications (65%), osteopenia or fractures or both (27%), increased alkaline [annals.org]
- Developmental Delay
Symptoms may include developmental delay, intellectual disability, enlargement of the liver and spleen, joint restrictions, coarse facial features and heart problems. [choc.org]
delay Facial dysmorphism: frontal bossing, elongated skull, flattened nasal bridge, broad nasal tip, thickened gingiva, anteverted nostrils, constant nasal discharge, spaced and protruded eyes. [amboss.com]
These included coarse face, dysostosis multiplex, respiratory difficulty, proteinuria with glomerular foamy cells, neurological involvement with developmental delays, pyramidal signs, and severe chronic anemia. [ncbi.nlm.nih.gov]
Speech Therapy Weakened muscles and developmental delays related to glycogen storage disorders can impact speech. [dukehealth.org]
Respiratoric
- Respiratory Insufficiency
Later onset forms are characterized by skeletal muscle weakness, respiratory insufficiency and hepatomegaly. Cardiac involvement is usually absent or mild. [genedx.com]
Most relevant clinical findings were proximal muscle weakness, lower limb muscle weakness, difficulty in climbing stairs, respiratory insufficiency due to muscle weakness, edema of her lower limbs, impairment of activities of daily living, orthopnea, [revecuatneurol.com]
The juvenile/adult form presents between the first and seventh decades as a slowly progressive muscle weakness or with symptoms of respiratory insufficiency. There is no cardiac involvement with this form. [rarediseases.org]
Common manifestations include coarse facial features, neurodevelopmental delays and regression, joint contractures, organomegaly, stiff hair, progressive respiratory insufficiency (caused by airway obstruction and sleep apnea), cardiac valvular disease [msdmanuals.com]
Gastrointestinal
- Failure to Thrive
[…] to thrive, hypotonia, hepatomegaly, lactic acidosis, hypoglycemia Treatment: Avoidance of fasting, uncooked cornstarch *Gene has been identified, and molecular basis has been elucidated. [merckmanuals.com]
Infantile GSDII presents during the first weeks or months of life with poor feeding, failure to thrive, macroglossia, severe hypotonia, cardiomegaly, mild hepatomegaly, and respiratory insufficiency. [genedx.com]
The classical clinical presentation for GSD IV is hepatomegaly with failure to thrive, followed by progressive liver failure and death by the age of 5 years. 1 Variable expression of GSD IV has been reported. 2-4 A patient, diagnosed at the age of 2 years [adc.bmj.com]
Airway obstruction Failure to thrive Dysostosis multiplex Inguinal hernia Hepatosplenomegaly Corneal clouding Hepatosplenomegaly Carpal tunnel syndrome Aggressive behavior Hyperactivity No corneal clouding Diagnosis Increased urinary levels of dermatan [amboss.com]
Babies with this condition have severe developmental delay, weak muscle tone (hypotonia), and failure to gain weight and grow at the expected rate (failure to thrive). [ghr.nlm.nih.gov]
- Regurgitation
[…] and mild mitral regurgitation, fatty replacement of skeletal muscle, pulmonary insufficiency, skeletal myopathy and myotonic discharges in EMG. [revecuatneurol.com]
Ventricular hypertrophy and cardiomyopathy Individuals with GSD III do not develop valvular disease such as semilunar or atrioventricular valve regurgitation, but left ventricular hypertrophy (LVH) seems to be common in GSD III, although only a small [nature.com]
Liver, Gall & Pancreas
- Hepatomegaly
A glycogen build up is found in liver causing hepatomegaly. [edusanjalbiochemist.blogspot.com]
Number) Defective Proteins or Enzymes Defective Gene or Genes (Chromosomal Location) Comments GSD I (Von Gierke disease) Most common type of GSD I: Ia ( > 80%) Onset: Before 1 yr Clinical features: Before 1 yr, severe hypoglycemia, lactic acidosis, and hepatomegaly [merckmanuals.com]
Prognosis is good; adult patients have normal stature and minimal hepatomegaly. [ommbid.mhmedical.com]
Later onset forms are characterized by skeletal muscle weakness, respiratory insufficiency and hepatomegaly. Cardiac involvement is usually absent or mild. [genedx.com]
NLSD-M patients are mainly affected by progressive myopathy, cardiomyopathy and hepatomegaly. Mutations in the PNPLA2 gene cause variable phenotypes of NLSD-M. [ncbi.nlm.nih.gov]
- Hepatosplenomegaly
Airway obstruction Failure to thrive Dysostosis multiplex Inguinal hernia Hepatosplenomegaly Corneal clouding Hepatosplenomegaly Carpal tunnel syndrome Aggressive behavior Hyperactivity No corneal clouding Diagnosis Increased urinary levels of dermatan [amboss.com]
Here we describe two different clinical presentations of this disease: one case with a clear phenotype of familial hypercholesterolaemia and one case with hepatosplenomegaly from childhood onwards. [ncbi.nlm.nih.gov]
Case report A 16 month old boy presented with hepatosplenomegaly and hypotonia. 8 The combination of hepatosplenomegaly, disturbed muscle function, and the histological finding of cirrhosis and glycogen storage in the liver led to a diagnosis of GSD IV [adc.bmj.com]
Fetus
- Hydrops Fetalis
Abstract Nonimmune hydrops fetalis is the most severe clinical manifestation of lysosomal storage diseases (LSDs). Around 14 different LSDs have been accounted for as 1-15% of the cause of nonimmune hydrops fetalis. [ncbi.nlm.nih.gov]
Differential diagnosis Differential diagnoses include galactosemia, hydrops fetalis, and tyrosinemia (see these terms).APBD can also present with or without GBE deficiency indicating that different biochemical defects could result in an identical phenotype [orpha.net]
Lysosomal diseases that can present with hydrops fetalis. History of recurrent non-immune hydrops fetalis. [cancertherapyadvisor.com]
Affected infants may have a condition called hydrops fetalis in which excess fluid accumulates in the body before birth. Children with this severe form of the condition usually live only into early childhood. [ghr.nlm.nih.gov]
Skin
- Angiokeratoma
Hexosaminidase A → ↑ GM2 ganglioside Progressive neurodegeneration Cherry-red spot on macula “Onion-skin” lysosomes Fabry disease X-linked recessive ↓ α-Galactosidase A → ↑ ceramide trihexoside Early symptoms: Dysesthesia (Fabry crises) Hypohidrosis Angiokeratomas [amboss.com]
Fabry disease (301500) Trihexosylceramide α-galactosidase GLA (Xq22)* Onset: Childhood or adolescence Urine metabolites:Globosylceramide Clinical features: Painful crisis involving extremities and abdomen precipitated by stress, fatigue, or exercise; angiokeratoma [msdmanuals.com]
Clinical features include coarse facial features, macular cherry-red spots, angiokeratomas, dysostosis multiplex, epilepsy, myoclonus, and ataxia. [emedicine.medscape.com]
Angiokeratomas are small, dark red micro vessel telangectasias, which can be mistaken by regular petechiae. It can become papular and rough on exam. [cancertherapyadvisor.com]
Eyes
- Corneal Opacity
opacities, gingival hyperplasia, joint contractures, osteoporosis, kyphoscoliosis, vertebral compression, carpotarsal osteolysis, ankylosis of small joints of feet, diffuse thickened skin, hyperpigmentation, hypertrichosis Treatment: Supportive care [msdmanuals.com]
Frequent clinical findings include recurrent bacterial infections, deafness, hepatomegaly, and lenticular or corneal opacities. [emedicine.medscape.com]
Ocular manifestations – Wearing peaked caps or eye-shades can reduce glare resulting from corneal clouding. Corneal transplantation is successful for individuals with attenuated disease, although donor grafts eventually become cloudy. [cancertherapyadvisor.com]
Ocular manifestations - Wearing peaked caps or eye-shades can reduce glare resulting from corneal clouding. Corneal transplantation is successful for individuals with attenuated disease, although donor grafts eventually become cloudy. [clinicaladvisor.com]
Ears
- Hearing Impairment
Mucopolysaccharidoses Mucopolysaccharidoses are a group of metabolic disorders that result in the impaired breakdown of glycosaminoglycans (previously known as mucopolysaccharides), due to mutations in lysosomal enzymes. [amboss.com]
Renal manifestations: Patients with Fabry disease can present with progressive end-stage renal disease associated with other symptoms (hypertrophic cardiomyopathy, arrhythmias, hearing impairment, acroparesthesias) and X-linked inheritance in family history [cancertherapyadvisor.com]
Musculoskeletal
- Genu Valgum
Intervention with custom-molded foot orthoses may improve distal alignment at feet and ankles and secondarily decrease genu valgum, leading to improved weight-bearing alignment for protection of the musculoskeletal system over time. [nature.com]
Clinical manifestations include short stature, pectus carinatum, forearm deformity, genu valgum, scoliosis, hip dysplasia, odontoid hypoplasia with atlantoaxial instability, and dental abnormalities. [ncbi.nlm.nih.gov]
- Muscle Spasticity
Signs and symptoms of Salla disease include intellectual disability and developmental delay, seizures, problems with movement and balance (ataxia), abnormal tensing of the muscles (spasticity), and involuntary slow, sinuous movements of the limbs (athetosis [ghr.nlm.nih.gov]
Neurologic
- Neurologic Manifestation
manifestations in lysosomal storage disorders [ldnz.org.nz]
Neurological Syndrome in LSDs Characteristics of neurological manifestations of LSDs are: – Most children have normal development for an initial and variable period. – At the onset of disease, global developmental delay is usually very subtle. – Once [cancertherapyadvisor.com]
Neurological Syndrome in LSDs Characteristics of neurological manifestations of LSDs are: - Most children have normal development for an initial and variable period. - At the onset of disease, global developmental delay is usually very subtle. - Once [clinicaladvisor.com]
Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C: an observational cohort study. [ncbi.nlm.nih.gov]
- Paresthesia
The reactions include one or more of the following: chills, fever, feeling hot or cold, dyspnea, nausea, flushing, headache, vomiting, paresthesia, fatigue, pruritus, pain in extremity, hypertension, chest pain, throat tightness, abdominal pain, dizziness [cancertherapyadvisor.com]
Workup
The present review focuses on current available evidence that supports the incremental value of STE in the diagnostic and prognostic workup of LVH. [ncbi.nlm.nih.gov]
The coexistence of hepatomegaly and hypoglycemia should prompt a workup that includes measurement of BG, lactate, uric acid, and hepatic profile including liver function studies, CK, plasma total and free carnitine, acylcarnitine profile, urinalysis, [nature.com]
Ultrasound
- Enlargement of the Liver
Symptoms may include developmental delay, intellectual disability, enlargement of the liver and spleen, joint restrictions, coarse facial features and heart problems. [choc.org]
Symptoms and signs depend upon the exact type but can include enlargement of the liver (hepatomegaly), hypoglycemia, and muscle weakness or cramps eventually accompanied by muscle wasting. [medicinenet.com]
Mucopolysaccharide storage disease – A group of conditions that can cause mental retardation, visual problems, bone deformities, liver and spleen enlargement and reduced life span. [pediatrics.northwell.edu]
Later, there may be a gradual coarsening of facial features, an enlarged tongue (macroglossia) and enlargement of the liver (hepatomegaly). [rarediseases.org]
Treatment
The goal of treatment is to maintain normal blood glucose levels. [chp.edu]
A variety of treatment regimes including chaperone therapies, enzyme replacement therapy, and substrate inhibition therapy are currently under development for many LSDs. [genetics.emory.edu]
Mount Sinai Hospital has been an international leader in the management and treatment of these rare disorders and has been a referral center for patients from all over the world. [mountsinai.org]
Prognosis and treatment of glycogen storage diseases vary by type, but treatment typically includes dietary supplementation with cornstarch to provide a sustained source of glucose for the hepatic forms of GSD and exercise avoidance for the muscle forms [merckmanuals.com]
Prognosis
Prognosis Prognosis is unfavorable for patients with perinatal onset and classic forms who do not undergo liver transplantation. Long-term prognosis for others depends on the extent, severity, and progression of the condition. [orpha.net]
Prognosis The prognosis of GSD is highly varied. Overall, the long-term prognosis depends on the extent, severity, and progression of the disease. GSDs are generally multisystem diseases, with many potential complications. [encyclopedia.com]
In patients with LVH, subclinical left ventricular (LV) dysfunction despite normal ejection fraction (EF) may be present before the onset of symptoms, which portends a dismal prognosis. [ncbi.nlm.nih.gov]
Etiology
This case illustrates a rare etiology of storage disease that causes abnormal liver function tests. [ncbi.nlm.nih.gov]
There are three main classes, which include: [1] Gaucher disease Etiology: autosomal recessive inherited disease [2] Epidemiology Pathophysiology: deficiency of β-glucocerebrosidase → accumulation of glucocerebroside in the brain, liver, spleen, bone [amboss.com]
Etiology NLSDI/Dorfman-Chanarin disease is caused by mutations in the ABHD5 gene (3p21), NLSDM by mutations in the PNPLA2/ATGL gene (localized to 11p15.5). [orpha.net]
Epidemiology
This report expands the epidemiology of FSD and demonstrates idiosyncrasy in response to oral carbamazepine and/or ursodeoxycholic acid in FSD. [ncbi.nlm.nih.gov]
There are three main classes, which include: [1] Gaucher disease Etiology: autosomal recessive inherited disease [2] Epidemiology Pathophysiology: deficiency of β-glucocerebrosidase → accumulation of glucocerebroside in the brain, liver, spleen, bone [amboss.com]
Summary Epidemiology The group of diseases is very rare and the prevalence is unknown (around 50 cases have been reported in medical literature, of which 3 had NLSDM) because of the vagueness of the descriptions. [orpha.net]
GSD I is typically treated with frequent small meals of carbohydrates and cornstarch to prevent low blood sugar, while other treatments may include allopurinol and human granulocyte colony stimulating factor. [21] Epidemiology [ edit ] Overall, according [en.wikipedia.org]
Pathophysiology
Although the exact pathophysiology is not exactly the same, it is astounding how many similar pathways are altered in all of these diseases. [ncbi.nlm.nih.gov]
Overview Lysosomal storage diseases Disease Inheritance Pathophysiology Main findings Sphingolipidoses Gaucher disease Autosomal recessive ↓ β-Glucocerebrosidase → ↑ glucocerebroside Hepatosplenomegaly Bone crises Blood cytopenias Gaucher cells Krabbe [amboss.com]
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test Glycogen storage diseases (GSDs) are a group of inherited metabolic conditions caused by deficiency of enzymes responsible for [mayomedicallaboratories.com]
This may exacerbate subtle energy deficiency which has been discussed to play a pathophysiological role in glycogenoses [ 21 ],[ 22 ]. [ojrd.biomedcentral.com]
Manifestations Although single gene defects typically result in substrate accumulation, the precise underlying pathophysiologic mechanisms that lead to clinical symptoms are not entirely clear. [emedicine.medscape.com]
Prevention
Conclusions: For GSD-Ia, hyperuricemia and pyelonephritis should be treated to prevent nephrocalcinosis and additional renal damage. For GSD-Ib, granulocyte-colony-stimulating factor may prevent bacterial infections. [annals.org]
There is no way to prevent GSDs. [mda.org.au]
High-molecular-weight PVP polymers are prevented from renal excretion and are retained in the reticuloendothelial system. [ncbi.nlm.nih.gov]
Weinstein’s research lab, located at UConn Health, focuses on ways to prevent the complications of the disease—and on discovering a cure. [connecticutchildrens.org]
This is done to prevent gout and kidney stones. Type IV is sometimes treated with liver transplantation. [chp.edu]