The second group of patients usually present within the first 24-48 hours of life with hypotonia, tachypnea, hepatomegaly, metabolic acidosis and hypoketotic hypoglycemia. [orpha.net]

It has a heterogeneous clinical presentation, with at least three different phenotypic appearances. [unboundmedicine.com]

Milder forms may present in childhood or later. EMA encephalopathy presents in infancy with developmental delay, diarrhea and petechiae. [dnadvent.com]

Reported here is a novel presentation of late onset glutaric aciduria type 2 in two Thai siblings. A 9-year-old boy presented with gradual onset of proximal muscle weakness for 6 weeks. [ncbi.nlm.nih.gov]

• Poor Feeding

  Clinical Considerations: GA2/MADD often presents in the neonate with poor feeding, marked lethargy, and facial and renal dysmorphism. Laboratory tests will reveal hypoketotic hypoglycemia, metabolic acidosis and hyperammonemia. [dnadvent.com]

  In most cases, the condition appears in infancy or early childhood as a sudden episode called a metabolic crisis which causes weakness; behavior changes such as poor feeding and decreased activity; and vomiting. [rarediseases.info.nih.gov]

• Movement Disorder

  Use of baclofen and benzodiazepines are often first line therapies for the movement disorder associated dystonia and spasticity. [clinicaladvisor.com]

  Spectrum of movement disorders associated with glutaric aciduria type 1: A study of 16 patients. Mov. Disord.: Off. J. Mov. Disord. [mdpi.com]

  Spectrum of movement disorders associated with glutaric aciduria type 1: a study of 16 patients. Mov Disord. 2008 Dec 15;23(16):2392–7. 5. Neumaier-Probst E, Harting I, Seitz A, et al. [nzma.org.nz]

  disorder Treatment consists of fasting avoidance, carnitine and riboflavin supplements. [medicalhomeportal.org]

  A defect in pyruvate decarboxylase in a child with an intermittent movement disorder. J. Clin. Invest. 49 (1970) 423–432 PubMed Google Scholar Blass, J. P., Schulman, J. D., Young, D. S. and Hom, E. [link.springer.com]

• Odor of Sweaty Feet

  Evaluate infant (“sweaty feet” odor, facial dysmorphism, failure to thrive, lethargy, hypoketotic hypoglycemia, metabolic acidosis, hyperammonemia). [dnadvent.com]

  They may also emit an odor resembling sweaty feet. Others have a less severe form which may appear in infancy, childhood, or even adulthood. [rarediseases.info.nih.gov]

• Swelling

  In clinically severely affected children, bilateral basal ganglia abnormalities are seen, with initial swelling that subsequently progresses to atrophy and necrosis. [radiopaedia.org]

  Generally, there is no regional predominance, rather, there is a diffuse involvement of the white matter with marked swelling early in the course of the disease. [ijri.org]

  On the other hand, a slight reduction of previously described subcortical diffusion restriction, and reduced swelling of corpus callosum were observed. [doi.org]

  […] the muscles rigid muscle contractions called spasticity involuntary jerking movements of the arms and legs, called dystonia poor coordination and balance problems increased levels of acidic substances in the blood, called metabolic acidosis seizures swelling [newbornscreening.info]

• Multiple Congenital Anomalies

  Complete enzyme defects, especially of ETF-QO, are often associated with multiple congenital anomalies, including renal cystic dysplasia, and death in infancy. [ommbid.mhmedical.com]

• Tachypnea

  The second group of patients usually present within the first 24-48 hours of life with hypotonia, tachypnea, hepatomegaly, metabolic acidosis and hypoketotic hypoglycemia. [orpha.net]

  In the neonatal without anomalies form, illness generally presents within the first few days, including: Hypotonia Tachypnea Metabolic acidosis Hepatomegaly Sweaty feet odor Lab findings: Metabolic acidosis Hypoglycemia Those with mild or late-onset form [medicalhomeportal.org]

• Hepatomegaly

  The second group of patients usually present within the first 24-48 hours of life with hypotonia, tachypnea, hepatomegaly, metabolic acidosis and hypoketotic hypoglycemia. [orpha.net]

  Liver transplantation Carnitine palmitoyltransferase I (CPT-I) deficiency (255120*) CPT-I Biochemical profile: Normal to elevated total and free plasma carnitine, no dicarboxylic aciduria Clinical features: Fasting intolerance, hypoketotic hypoglycemia, hepatomegaly [merckmanuals.com]

• Myopathy

  Late onset glutaric aciduria type 2, a rare cause of muscle weakness in children, should be included in the differential diagnosis of myopathy. [ncbi.nlm.nih.gov]

  […] phenotypes include the neonatal-onset (lethal) form with congenital abnormalities (type I), the neonatal-onset form with hypoketotic hypoglycemia without congenital abnormalities (type II), and the late-onset form presenting with progressive proximal myopathy [medlink.com]

  Riboflavin-responsive lipid-storage myopathy and glutaric aciduria type II of early adult onset. Neurology. 1986 ;36: 367 – 372. Google Scholar | Crossref | Medline 8. Dusheiko, G, Kew, MC, Joffe, BI. [journals.sagepub.com]

  Two eminently treatable genetic metabolic myopathies. [neurologyindia.com]

  […] onset of intermittent episodes of vomiting, metabolic acidosis and hypoketotic hypoglycaemia (+/- cardiac involvement) during the first few months of life to adolescent/adult presentation with acute Reye-like illness with ketoacidosis and lipid storage myopathy [orpha.net]

• Myalgia

  Blockage of the Esophagus Blockage or Narrowing of the Duodenum Narrowing of Opening Between Stomach and Small Intestine Appendicitis Inflammatory Bowel Disease Paralysis of the Intestines Stomach or Intestine Blockage PKU - Phenylketonuria Eosinophilia Myalgia [webmd.com]

• Exercise-induced Muscle Pain

  muscle pain Movement disorder Treatment consists of fasting avoidance, carnitine and riboflavin supplements. [medicalhomeportal.org]

• Depressed Nasal Bridge

  Initial signs and symptoms may include: In the neonatal with anomalies form : Facial dysmorphism - high forehead, depressed nasal bridge, low-set abnormally formed ears Rocker bottom feet Muscular defects of the abdominal wall Renal anomalies Anomalies [medicalhomeportal.org]

  nasal bridge Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ] 0005280 Developmental cataract Clouding of the lens of the eye at birth 0000519 Electron transfer [rarediseases.info.nih.gov]

As such, their presentation at emergency departments may initiate a protocol for workup of possible child abuse. [clinicaladvisor.com]

Diagnostics: Initial workup in the emergency room included the following: A pH of 7.29 with a pCO 2 of 30, pO 2 46, Serum bicarbonate 14.6. Hemoglobin 13.3, WBC 7.7. [eplabdigest.com]

• Enlargement of the Liver

  […] of their liver. [disabled-world.com]

  There may also be enlargement of the liver, heart failure, and a characteristic odor resembling that of sweaty feet. [en.wikipedia.org]

• Hypoketotic Hypoglycemia

  Educate family about signs and symptoms of hypoglycemia and metabolic acidosis (“sweaty feet” odor, facial dysmorphism, failure to thrive, lethargy, hypoketotic hypoglycemia, metabolic acidosis, hyperammonemia. [dnadvent.com]

  Clinical manifestations thus include fasting hypoglycemia, severe metabolic acidosis, and hyperammonemia. [merckmanuals.com]

  The second group of patients usually present within the first 24-48 hours of life with hypotonia, tachypnea, hepatomegaly, metabolic acidosis and hypoketotic hypoglycemia. [orpha.net]

Management and treatment Treatment for the more severe phenotypes involves restriction of both fat and protein and reliance on a high carbohydrate diet. Strict avoidance of fasting and of other precipitating stresses is essential. [orpha.net]

Table 1 presents the metabolic parameters in blood and urine during the different phases of 3-HB treatment. [doi.org]

The boy recovered completely after treatment. Later, his younger sibling became symptomatic; the same diagnosis was confirmed, and treatment was similarly effective. [ncbi.nlm.nih.gov]

Prognosis MADD-S is invariably fatal. Milder phenotypes have a more favorable prognosis. The documents contained in this web site are presented for information purposes only. [orpha.net]

The severity of the mutation to the gene will determine how severe the symptoms of GA-2 are and also determine the prognosis (Man-Chun, 1992). The most severe GA-2 is apparent at or shortly after birth. [sites.google.com]

Etiology MADD is caused by mutations in the ETFA (15q23-q25), ETFB (19q13.3-q13.4) and ETFDH (4q32-q35) genes which encode the alpha and beta subunits of electron transfer flavoprotein (ETF) and ETF-coenzyme Q oxidoreductase. [orpha.net]

We conclude that amino and organic acids in urine should be investigated in all children with progressive macrocephaly of unknown etiology to rule out glutaric aciduria type I. [analesdepediatria.org]

Summary Epidemiology Birth prevalence is estimated at 1/200,000 but great variation is seen between countries/ethnicities. [orpha.net]

Epidemiology Type I – very rare. [patient.info]

The pathophysiology of this condition and potential treatment options are discussed. [academic.oup.com]

who pioneered the use of IVB and demonstrated that it is more effective for treating secondary dystonias in children than the intrathecal route of baclofen delivery. [5] Importantly, 2 of their study subjects with neurogenetic disorders that share pathophysiological [movementdisorders.org]

Molecular and metabolic pathophysiology MADD is an autosomal recessive disorder that results from a defect of electron transfer from the primary flavoprotein dehydrogenases to coenzyme Q10 in the mitochondrial electron transport chain. [1], [2], [3] The [neurologyindia.com]

GA1 in some patients may be caused by large deletions or intron mutations that are not susceptible to simple PCR analysis. 11 Direct measurement of GDH activity in fibroblasts or lymphocytes remains the diagnostic method of choice as it reflects the pathophysiology [jmg.bmj.com]

Here we present an infant with MADD in whom the previously reported dose of 3-HB did not prevent the acute, severe, metabolic decompensation or progressive cardiomyopathy in the subsequent months. [ncbi.nlm.nih.gov]

Therefore, prevention of reaching this catabolic threshold seems to be the best therapeutic option in most, but not all patients. [clinicaladvisor.com]

Conclusions The previously recommended dose of 900 mg/kg of 3-HB per day did not prevent the progressive cardiomyopathy. [doi.org]