The intermittent form presents with encephalopathy and metabolic disturbances when the patient undergoes catabolic stress. [genedx.com]

Comprising 31 clinical protocols from the world's foremost clinical geneticists, Signs and Symptoms of Genetic Conditions provides a practical manual for the diagnosis and management of common human genetic conditions based on their presenting signs and [books.google.com]

Intermediate have the maple syrup odor to their urine and may also present with developmental delay and feeding problems in infancy. Oftentimes they are diagnosed with MSUD between 5 months and 7 years old, presenting with intellectual disability. [thinkgenetic.com]

[…] ranges from a severe neonatal presentation with neurological deficits to a less severe childhood presentation with exertional fatigue between decompensation episodes. Patients may also present with severe liver failure. [quizlet.com]

The clinical presentation is very similar to that of intermediate maple syrup urine disease, with the exception of early-onset lactic acidosis. [emedicine.medscape.com]

• Weight Loss

  Some of the initial symptoms of classic MSUD include irregular sleep patterns, lethargy, irritability, weight loss, poor appetite, and a distinctive maple sugar odor in earwax, sweat, and urine (which gives the disorder its name). [medicaldaily.com]

  With progress of the disease it comes to weight loss and progressive neurological deterioration and hypo- to hypertonia. If the disease is not treated it leads to coma and death within several months after birth. [i12r-studfilesrv.informatik.tu-muenchen.de]

  Some common symptoms of classic MSUD are: Extreme fatigue, irritability and lethargy High pitched cry Poor feeding, loss of appetite and weight loss Irregular sleep rhythm Poor suckling Alternating episodes of hypotonia (flaccidity of muscles) and hypertonia [drelist.com]

  Within several days, the infant will show poor feeding, vomiting, and irritability, followed by lack of energy, weight loss, seizures, a tense arched posture, muscle tone which alternates between stiff and limp, and swelling of the brain. [counsyl.com]

  Clinical presentation of classic MSUD includes - Poor sucking with little interest in feeding Marked lethargy Weight loss Vomiting Rapid shallow respirations High-pitched cry Hypotonia alternating with periods of hypertonicity Dystonic posturing of the [motherbabyuniversity.com]

• Anorexia

  MAPLE-syrup-urine disease (branched-chain ketonuria) is a genetic disorder with a well defined biochemical defect. 1 Symptoms of anorexia, vomiting, hypertonicity and occasionally convulsions appear during the first week of life. [nejm.org]

  These precipitating factors can lead to a potentially fatal episode of acute decompensation with anorexia, nausea, vomiting, lethargy, ataxia (in infants/toddlers), cognitive impairment, sleep disturbances, hallucinations, hyperactivity, mood swings, [orpha.net]

  If left untreated further symptoms may develop including nausea, anorexia, dystonia, ataxia, cognitive impairment, hallucinations, and sleep disturbances. [thinkgenetic.com]

  The intermediate and intermittent forms are milder and may present with anorexia, poor growth, irritability or developmental delay later in infancy or childhood, frequently in response to stress; however, even patients who are without symptoms can develop [genedx.com]

  Those with MSUD must be hospitalised for intravenous infusion of sugars and nasogastric drip-feeding of formula, in the event of metabolic decompensation, or anorexia, diarrhea or vomiting. [en.wikipedia.org]

• High-Pitched Cry

  Other important syptoms are poor feeding, poor appetite, weak suck, lethargy, high pitched cry, and movements that look like fencing or bicycling. [maplesyrupurine.weebly.com]

  Some common symptoms of classic MSUD are: Extreme fatigue, irritability and lethargy High pitched cry Poor feeding, loss of appetite and weight loss Irregular sleep rhythm Poor suckling Alternating episodes of hypotonia (flaccidity of muscles) and hypertonia [drelist.com]

  Clinical presentation of classic MSUD includes - Poor sucking with little interest in feeding Marked lethargy Weight loss Vomiting Rapid shallow respirations High-pitched cry Hypotonia alternating with periods of hypertonicity Dystonic posturing of the [motherbabyuniversity.com]

  […] classic MSUD are: lethargy poor appetite weight loss weak sucking ability irritability a distinctive maple sugar odor in earwax, sweat, and urine irregular sleep patterns alternating episodes of hypertonia (muscle rigidity) and hypotonia (muscle limpness) high-pitched [healthline.com]

  The symptoms of this disease include urine that smells like maple syrup, avoiding food or feeding difficulties, coma, high pitched crying, lethargy, poor weight gain, seizures and vomiting (Park, H.D. et al., 2011). [ukessays.com]

• Feeding Difficulties

  Symptoms Avoiding food Coma Feeding difficulties Lethargy Seizures Urine that smells like maple syrup Vomiting Exams and Tests Plasma amino acid test Urine amino acid test There will be signs of ketosis and excess acid in blood (acidosis). [dxline.info]

  Symptoms * Avoiding food * Coma * Feeding difficulties * Lethargy * Seizures * Urine that smells like maple syrup * Vomiting Exams and Tests * Urine amino acid test * Plasma amino acid test There will be signs of ketosis and acidosis (excess acid in blood [welltellme.com]

  The symptoms of this disease include urine that smells like maple syrup, avoiding food or feeding difficulties, coma, high pitched crying, lethargy, poor weight gain, seizures and vomiting (Park, H.D. et al., 2011). [ukessays.com]

  […] months in 50% CNS: Spastic ataxia Ataxia Eye Optic Atrophy: Vision loss Conjunctivitis Hearing Loss Developmental Delay Hypotonia Myelopathy Quadriplegia Spasticity Recurrent exacerbations Systemic features Skin: Alopecia; Rash GI: Hepato-Splenomegaly; Feeding [neuromuscular.wustl.edu]

  The condition appears in early infancy, where it is characterized by feeding difficulties and avoidance of food, vomiting, seizures, lack of energy, and even coma. [cags.org.ae]

• Surgical Procedure

  This major surgical procedure is associated with risks, and individuals who have had a liver transplant must take medication for the rest of their lives to prevent their body from rejecting the donor liver. [flipper.diff.org]

  These should be treated as appropriate – infection should be treated with antibiotics; before surgical procedures, the patient should receive IV fluid with 10% dextrose which should be continued during and after surgery; and dietary changes should be [dovepress.com]

• Loss of Appetite

  Some of the initial symptoms of classic MSUD include irregular sleep patterns, lethargy, irritability, weight loss, poor appetite, and a distinctive maple sugar odor in earwax, sweat, and urine (which gives the disorder its name). [medicaldaily.com]

  Some common symptoms of classic MSUD are: Extreme fatigue, irritability and lethargy High pitched cry Poor feeding, loss of appetite and weight loss Irregular sleep rhythm Poor suckling Alternating episodes of hypotonia (flaccidity of muscles) and hypertonia [drelist.com]

• Epigastric Pain

  Individuals with the classic neonatal form have 14, 15 In older individuals, increased levels of leucine (leucinosis) causes epigastric pain, anorexia, vomiting, muscle fatigue, altered level of consciousness, psychiatric symptoms, movement disorders, [dovepress.com]

• Muscle Spasm

  spasms, and seizures Infants with MSUD who remain untreated will die within the first few months of their lives. [disabled-world.com]

  spasms, poor coordination, coma, brain damage, and death. [acertx.com]

• Muscle Hypotonia

  Patients have hypotonia, progressive muscle weakness, developmental delay and, possibly seizures. Failure to thrive, vomiting, and hypoglycemia may be seen. [genico.ch]

• Cutaneous Manifestation

  Al Awamy and Al-Madan (2002) concluded that both patients had MSUD with acrodermatitis enteropathica-like cutaneous manifestation, most probably related to isoleucine deficiency. [cags.org.ae]

• Neonatal Onset

  Classical MSUD has a neonatal onset of encephalopathy and is the most severe and most common form. Variant forms of MSUD generally have the initial symptoms by 2 years of age. [www4.utsouthwestern.edu]

  Classic MSUD represents most known cases and presents in the neonatal period following protein catabolism. Affected neonates present within the first 48 hours of life with irritability, poor feeding, and rapid onset of ketoacidosis. [invitae.com]

  Classic Classic MSUD is defined by neonatal onset of encephalopathy and is the most severe form of the disorder. [themedicalbiochemistrypage.org]

  The patients with the classical form of MSUD (4 males, 3 females; 13 ± 4 years) were characterized by neonatal onset of the disease, very low protein tolerance, and residual l- [1- 14 C]leucine oxidation in cultured fibroblasts of 12 )]. [clinchem.aaccjnls.org]

  Clinical The presentation of malonic aciduria due to MCD deficiency is variable, ranging from an acute neonatal onset to later in childhood. [genico.ch]

• Ataxia

  The clinical picture was characterized by seizure-like episodes of confusion and intermittent ataxia. The diagnosis was made by showing an increased excretion of branched-chain alpha-hydroxy acids as well as Ataxia. [herbal-organic.com]

  Coverage includes separate chapters on autism, autosomal recessive ataxias, and autosomal dominant ataxias, and new chapters on endovascular neuroradiology, parkinsonian syndromes, Lewy body dementias, frontotemporal dementia, vanishing white matter, [books.google.com]

  Home, Search, Index, Links, Pathology, Molecules, Syndromes, Muscle, NMJ, Nerve, Spinal, Ataxia, Antibody & Biopsy, Patient Info METABOLIC ATAXIAS Hartnup ● SLC6A19 ; Chromosome 5p15.33; Recessive SLC6A19 protein Na+-dependent amino acid transporter Transports [neuromuscular.wustl.edu]

  The patients had episodes with neurological symptoms including lethargy and/or ataxia during childhood infections. All seven patients were heterozygous for the annotated R301C mutation. [ncbi.nlm.nih.gov]

• Dystonia

  Later, catabolic stress, infection or injury may cause acute, potentially fatal, leucine intoxication with vomiting, altered consciousness, ataxia and acute dystonia in toddlers and hallucinations, hyperactivity, focal dystonia, ataxia and choreoathetosis [orpha.net]

  BCAA, leucine, isoleucine & valine Clinical Features Onset age: During 2nd year Intermittent events Ataxia, Mitochondrial Drowsiness Seizures Attacks after infection, surgery, high protein Patients without therapy Mental retardation Extrapyramidal: Dystonia [neuromuscular.wustl.edu]

  If left untreated further symptoms may develop including nausea, anorexia, dystonia, ataxia, cognitive impairment, hallucinations, and sleep disturbances. [thinkgenetic.com]

  Early signs and symptoms are poor feeding, vomiting, lethargy, hypo or hypertonia, dystonia, seizures and encephalopathy which can lead to early death or permanent neurologic damage. Later in infancy or childhood, developmental delays are noted. [secure.ssa.gov]

• Neonatal Seizures

  The classic form presents in the first week of life with ketoacidosis, hypoglycemia, emesis, neonatal seizures, and hypertonia. The intermediate and intermittent forms present in childhood or later with acute episodes of ataxia and vomiting. [profiles.umassmed.edu]

  Neonatal "seizure" while riding in a car: A peculiar but key episode for diagnosis of benign neonatal sleep myoclonus. Clin Pediatr (Phila). 53:605-606‚ 2014 ● Abe Y‚ Kobayashi S‚ Wakusawa K‚ Tanaka S‚ Inui T‚ Yamamoto T‚ Kunishima S‚ Haginoya K. [ped.med.tohoku.ac.jp]

• Opisthotonus

  Classic MSUD presents in the first days of life with poor feeding and drowsiness followed by a worsening encephalopathy with lethargy, intermittent apnea, stereotypic movements ("fencing" and ''bicycling") and opisthotonus. [tellmegen.com]

  Progressive encephalopathy with lethargy, intermittent apnea, stereotyped movements (described as "fencing" and bicycling") and opisthotonus occur in the first few days of life. [orpha.net]

  The symptomes of MSUD are mental and physical retardation, feeding problems, vomiting, dehydration, lethargy, hypotonia, seizures, hypoglycaemia, ketoacidosis, opisthotonus, pancreatitis, coma and neurological decline. [i12r-studfilesrv.informatik.tu-muenchen.de]

  […] inappropriate, extreme or erratic behaviour and moods, hallucinations, anorexia, weight loss, [4] anemia, diarrhea, vomiting, [5] dehydration, lethargy, [4] oscillating hypertonia and hypotonia, [4] ataxia, [4] seizures, [4] hypoglycaemia, ketoacidosis, opisthotonus [en.wikipedia.org]

• Cerebellar Ataxia

  Gait disorder; Dysarthria; Progressive Motor & Speech delay Hypotonia Seizure: 1 patient Laboratory Glutamine: High Brain: Cerebellar atrophy in 1 patient Also see: Recessive Ataxias Return to Ataxia Syndromes Return to Neuromuscular Home Page References [neuromuscular.wustl.edu]

Biochemical workup MSUD in a newborn may be suspected due to the presence of illness and/or an abnormal neonatal screening test result. [dovepress.com]

Workup of such patients includes measuring plasma amino acids and looking for succinylacetone on urine organic acid analysis. [genico.ch]

• Hyponatremia

  As serum sodium approaches 140-145 meq/L, reduce IV fluids to D10/ 1/2 normal saline and monitor serum sodium closely (hyponatremia enhances brain edema). After 24 hours, adjust sodium intake to provide 4 meq/kg/day. [newenglandconsortium.org]

Management and treatment Patients with intermittent MSUD tolerate a normal intake of leucine and treatment is not necessary. [orpha.net]

Treatment When the condition is diagnosed, and during episodes, treatment involves eating a protein-free diet. Fluids, sugars, and possibly fats are given through a vein (IV). [dxline.info]

ACER-001 was granted orphan drug designation as a potential treatment for MSUD in 2014. [acertx.com]

Prognosis The prognosis is good if metabolic control is maintained during times of stress and any episodes of acute decompensation are immediately treated. The documents contained in this web site are presented for information purposes only. [orpha.net]

[…] exhibit high diffusion signal MR spectroscopy: single-voxel proton MR spectroscopy may show the presence of branched-chain amino acids and branched-chain alpha-keto acids resonating at 0.9-1.0 ppm, especially during a metabolic crisis 1,2 Treatment and prognosis [radiopaedia.org]

Outlook (Prognosis) This disease can be life threatening if untreated. Even with dietary treatment, stressful situations and illness can still cause high levels of certain amino acids. Death may occur during these episodes. [dxline.info]

What is the prognosis for a person with Maple Syrup Urine Disease Type 1B? With early, careful, and lifelong treatment, people with MSUD type 1B can live healthy lives into adulthood and show normal growth and mental development. [counsyl.com]

In 183 short chapters, the book provides the essentials clinicians need on symptoms/signs, diagnostic tests, and neurologic disorders of all etiologies. For this edition, Timothy A. [books.google.com]

Etiology MSUD is due to mutations in genes encoding 3 of the 4 subunits of the branched-chain 2-ketoacid dehydrogenase (BCKAD) complex. [orpha.net]

Oltarzewski-M; Lenartowska-I Evaluation of the usefulness for neonatal mass screening in light of 35 years personal experience Med-Wieku-Rozwoj. 1999 Oct-Dec; 3(4): 529-59 Lebo-RV; Shapiro-LR; Fenerci-EY; Hoover-JM; Chuang-JL; Chuang-DT; Kronn-DF Rare etiology [malattierare.regione.veneto.it]

The etiology in 70 to 80% of the non-familial cases is unknown. [genico.ch]

[…] deficiency - Intermittent MSUD - Intermittent branched-chain 2-ketoacid dehydrogenase deficiency Classification (Orphanet): - Inborn errors of metabolism - Rare genetic disease Classification (ICD10): - Endocrine, nutritional and metabolic diseases - Epidemiological [csbg.cnb.csic.es]

Specific mutation Epidemiology 25 year-old female: Treated for MSUD Onset Age: Young adult Course: Over days Clinical Weakness Legs > Arms Symmetric Severe Tendon reflexes: Reduced or Absent Sensory Loss: Pan-modal Pain: Later in course Cranial nerves [neuromuscular.wustl.edu]

Summary Epidemiology MSUD has an estimated incidence of 1/150,000 live births. There is no data to suggest what number of patients has intermittent MSUD but it is probably underdiagnosed. [orpha.net]

Screening for five prevalent mutations of SLC25A13 gene in Guangdong‚ China: A molecular epidemiologic survey of citrin deficiency. [ped.med.tohoku.ac.jp]

[…] of congenital insensitivity to pain with anhidrosis 2015 Neurobiology of pain and emotional response: lessons from the molecular pathophysiology of congenital insensitivity to pain with anhidrosis 2015 Congenital insensitivity to pain with anhidrosis [researchmap.jp]

Useful For Suggests clinical disorders or settings where the test may be helpful Follow-up of patients with maple syrup urine disease Monitoring of dietary compliance for patients with maple syrup urine disease Clinical Information Discusses physiology, pathophysiology [mayomedicallaboratories.com]

The pathophysiology of MSUD revolves around relative deficiency or absolute lack of enzyme that are collectively referred to as branched-chain alpha-ketoacid dehydrogenase complex (or BCKAD). [drelist.com]

Pathophysiology Catabolic stress such as normal perinatal catabolism or an acute illness (e.g. infection, injury, surgery, febrile illness) produces endogenous protein breakdown leading to increase in the BCAA and related branched chain ketoacids. [newenglandconsortium.org]

Dysarthria; Tremor Extrapyramidal: Athetosis; Dystonia Dementia Systemic features Liver Disease Hemolytic Anemia Treatment: Penicillamine A-β-lipoproteinemia (ABL) ● Microsomal Triglyceride Transfer Protein, large polypeptide (MTP) ; Chromosome 4q23 Pathophysiology [neuromuscular.wustl.edu]

The early detection of this rare disorder is important since control of branched chain amino acid intake may control metabolic abnormalities and prevent neurological damage. [ncbi.nlm.nih.gov]

Patients with increased BCAA levels often present with encephalopathy and require dialysis or haemofiltration to prevent brain damage. In this case haemofiltration was a preventative treatment of acute decompensation during the procedure. [raredisorders.imedpub.com]

A diet with minimal levels of the amino acids leucine, isoleucine, and valine must be maintained in order to prevent neurological damage. [welltellme.com]

Prevention Genetic counseling is suggested for people who want to have children and who have a family history of maple syrup urine disease. Many states now screen all newborns with blood tests for MSUD. [dxline.info]

Identifying the presence of MSUD at birth is critical to preventing long-term damage. [healthline.com]