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Dicarboxylic aciduria

MedGen UID:
343550
Concept ID:
C1856432
Finding
Synonym: Elevated urinary dicarboxylic acid level
 
HPO: HP:0003215

Definition

An increased concentration of dicarboxylic acid in the urine. [from HPO]

Conditions with this feature

Ariboflavinosis
MedGen UID:
20573
Concept ID:
C0035528
Disease or Syndrome
The concentration of vitamin B2 in the blood circulation is below the lower limit of normal.
Renal carnitine transport defect
MedGen UID:
90999
Concept ID:
C0342788
Disease or Syndrome
Systemic primary carnitine deficiency (CDSP) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. It encompasses a broad clinical spectrum including the following: Metabolic decompensation in infancy typically presenting between age three months and two years with episodes of hypoketotic hypoglycemia, poor feeding, irritability, lethargy, hepatomegaly, elevated liver transaminases, and hyperammonemia triggered by fasting or common illnesses such as upper respiratory tract infection or gastroenteritis. Childhood myopathy involving heart and skeletal muscle with onset between age two and four years. Pregnancy-related decreased stamina or exacerbation of cardiac arrhythmia. Fatigability in adulthood. Absence of symptoms. The latter two categories often include mothers diagnosed with CDSP after newborn screening has identified low carnitine levels in their infants.
Carnitine acylcarnitine translocase deficiency
MedGen UID:
91000
Concept ID:
C0342791
Disease or Syndrome
Carnitine-acylcarnitine translocase (CACT) is a critical component of the carnitine shuttle, which facilitates the transfer of long-chain fatty acylcarnitines across the inner mitochondrial membrane. CACT deficiency causes a defect in mitochondrial long-chain fatty acid ß-oxidation, with variable clinical severity. Severe neonatal-onset disease is most common, with symptoms evident within two days after birth; attenuated cases may present in the first months of life. Hyperammonemia and cardiac arrhythmia are prominent in early-onset disease, with high rates of cardiac arrest. Other clinical features are typical for disorders of long-chain fatty acid oxidation: poor feeding, lethargy, hypoketotic hypoglycemia, hypotonia, transaminitis, liver dysfunction with hepatomegaly, and rhabdomyolysis. Univentricular or biventricular hypertrophic cardiomyopathy, ranging from mild to severe, may respond to appropriate dietary and medical therapies. Hyperammonemia is difficult to treat and is an important determinant of long-term neurocognitive outcome. Affected individuals with early-onset disease typically experience brain injury at presentation, and have recurrent hyperammonemia leading to developmental delay / intellectual disability. Affected individuals with later-onset disease have milder symptoms and are less likely to experience recurrent hyperammonemia, allowing a better developmental outcome. Prompt treatment of the presenting episode to prevent hypoglycemic, hypoxic, or hyperammonemic brain injury may allow normal growth and development.
Deficiency of 3-hydroxyacyl-CoA dehydrogenase
MedGen UID:
266222
Concept ID:
C1291230
Disease or Syndrome
3-hydroxyacyl-CoA dehydrogenase deficiency is an inherited condition that prevents the body from converting certain fats to energy, particularly during prolonged periods without food (fasting).\n\nInitial signs and symptoms of this disorder typically occur during infancy or early childhood and can include poor appetite, vomiting, diarrhea, and lack of energy (lethargy). Affected individuals can also have muscle weakness (hypotonia), liver problems, low blood glucose (hypoglycemia), and abnormally high levels of insulin (hyperinsulinism). Insulin controls the amount of glucose that moves from the blood into cells for conversion to energy. Individuals with 3-hydroxyacyl-CoA dehydrogenase deficiency are also at risk for complications such as seizures, life-threatening heart and breathing problems, coma, and sudden death. This condition may explain some cases of sudden infant death syndrome (SIDS), which is defined as unexplained death in babies younger than 1 year.\n\nProblems related to 3-hydroxyacyl-CoA dehydrogenase deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.
Carnitine palmitoyl transferase 1A deficiency
MedGen UID:
316820
Concept ID:
C1829703
Disease or Syndrome
Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a disorder of long-chain fatty acid oxidation. Clinical manifestations usually occur in an individual with a concurrent febrile or gastrointestinal illness when energy demands are increased; onset of symptoms is usually rapid. The recognized phenotypes are: acute fatty liver of pregnancy, in which the fetus has biallelic pathogenic variants in CPT1A that causes CPT1A deficiency; and hepatic encephalopathy, in which individuals (typically children) present with hypoketotic hypoglycemia and sudden onset of liver failure. Individuals with hepatic encephalopathy typically present with hypoglycemia, absent or low levels of ketones, and elevated serum concentrations of liver transaminases, ammonia, and total carnitine. Between episodes of hepatic encephalopathy, individuals appear developmentally and cognitively normal unless previous metabolic decompensation has resulted in neurologic damage.
3-hydroxy-3-methylglutaryl-CoA synthase deficiency
MedGen UID:
414399
Concept ID:
C2751532
Disease or Syndrome
Mitochondrial HMG-CoA synthase deficiency (HMGCS2D) is an inherited metabolic disorder caused by a defect in the enzyme that regulates the formation of ketone bodies. Patients present with hypoketotic hypoglycemia, encephalopathy, and hepatomegaly, usually precipitated by an intercurrent infection or prolonged fasting (summary by Aledo et al., 2006).
Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins
MedGen UID:
480294
Concept ID:
C3278664
Disease or Syndrome
Acute infantile liver failure resulting from TRMU mutation is a transient disorder of hepatic function. In addition to elevated liver enzymes, jaundice, vomiting, coagulopathy, and hyperbilirubinemia, the presence of increased serum lactate is consistent with a defect in mitochondrial respiratory function. With supportive care, patients who survive the initial acute episode can recover and show normal development (Zeharia et al., 2009). See also transient infantile mitochondrial myopathy (MMIT; 500009), which is a similar disorder. A more severe, permanent disorder with some overlapping features is associated with mitochondrial DNA depletion (251880). See ILFS1 (615438) for information on syndromic infantile liver failure.
Peroxisome biogenesis disorder 13A (Zellweger)
MedGen UID:
766918
Concept ID:
C3554004
Disease or Syndrome
Zellweger syndrome (ZS) is an autosomal recessive multiple congenital anomaly syndrome resulting from disordered peroxisome biogenesis. Affected children present in the newborn period with profound hypotonia, seizures, and inability to feed. Characteristic craniofacial anomalies, eye abnormalities, neuronal migration defects, hepatomegaly, and chondrodysplasia punctata are present. Children with this condition do not show any significant development and usually die in the first year of life (summary by Steinberg et al., 2006). For a complete phenotypic description and a discussion of genetic heterogeneity of Zellweger syndrome, see 214100. Individuals with PBDs of complementation group K (CGK) have mutations in the PEX14 gene. For information on the history of PBD complementation groups, see 214100.
Very long chain acyl-CoA dehydrogenase deficiency
MedGen UID:
854382
Concept ID:
C3887523
Disease or Syndrome
Deficiency of very long-chain acyl-coenzyme A dehydrogenase (VLCAD), which catalyzes the initial step of mitochondrial beta-oxidation of long-chain fatty acids with a chain length of 14 to 20 carbons, is associated with three phenotypes. The severe early-onset cardiac and multiorgan failure form typically presents in the first months of life with hypertrophic or dilated cardiomyopathy, pericardial effusion, and arrhythmias, as well as hypotonia, hepatomegaly, and intermittent hypoglycemia. The hepatic or hypoketotic hypoglycemic form typically presents during early childhood with hypoketotic hypoglycemia and hepatomegaly, but without cardiomyopathy. The later-onset episodic myopathic form presents with intermittent rhabdomyolysis provoked by exercise, muscle cramps and/or pain, and/or exercise intolerance. Hypoglycemia typically is not present at the time of symptoms.
Acyl-CoA dehydrogenase 9 deficiency
MedGen UID:
1648400
Concept ID:
C4747517
Disease or Syndrome
MC1DN20 is an autosomal recessive multisystem disorder characterized by infantile onset of acute metabolic acidosis, hypertrophic cardiomyopathy, and muscle weakness associated with a deficiency of mitochondrial complex I activity in muscle, liver, and fibroblasts (summary by Haack et al., 2010). For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010.
Mitochondrial complex IV deficiency, nuclear type 22
MedGen UID:
1786100
Concept ID:
C5543491
Disease or Syndrome
Mitochondrial complex IV deficiency nuclear type 22 (MC4DN22) is an autosomal recessive metabolic disorder characterized by neonatal hypertrophic cardiomyopathy, encephalopathy, and severe lactic acidosis with fatal outcome (Wintjes et al., 2021). For a discussion of genetic heterogeneity of mitochondrial complex IV (cytochrome c oxidase) deficiency, see 220110.
Combined oxidative phosphorylation deficiency 59
MedGen UID:
1845781
Concept ID:
C5882730
Disease or Syndrome
Combined oxidative phosphorylation deficiency-59 (COXPD59) may present as a lethal infantile form of Leigh syndrome (see 256000) or as a milder disorder with hypertrophic cardiomyopathy, lactic acidosis, attention deficit-hyperactivity disorder (ADHD) and survival into adulthood (summary by Amarasekera et al., 2023). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).

Professional guidelines

PubMed

Inokuchi T, Yoshida I, Kaneko A, Tashiro K, Tashiro S, Jogo M, Aoki K, Tanaka M
J Chromatogr B Biomed Sci Appl 2001 Jul 5;758(1):57-60. doi: 10.1016/s0378-4347(01)00043-3. PMID: 11482735
Shimizu N, Yamaguchi S, Orii T
Acta Paediatr Jpn 1994 Apr;36(2):139-45. doi: 10.1111/j.1442-200x.1994.tb03149.x. PMID: 8203256
Duran M, De Klerk JB, Wadman SK, Bruinvis L, Ketting D
J Inherit Metab Dis 1984;7 Suppl 1:48-51. doi: 10.1007/BF03047374. PMID: 6434845

Recent clinical studies

Etiology

Anderson M, Eliot K, Kelly P, Shoemaker J
Nutr Clin Pract 2016 Dec;31(6):819-823. Epub 2016 Jul 9 doi: 10.1177/0884533616648330. PMID: 27153855
Desbats MA, Vetro A, Limongelli I, Lunardi G, Casarin A, Doimo M, Spinazzi M, Angelini C, Cenacchi G, Burlina A, Rodriguez Hernandez MA, Chiandetti L, Clementi M, Trevisson E, Navas P, Zuffardi O, Salviati L
Eur J Hum Genet 2015 Sep;23(9):1254-8. Epub 2015 Jan 7 doi: 10.1038/ejhg.2014.277. PMID: 25564041Free PMC Article
Huybrechts SJ, Van Veldhoven PP, Hoffman I, Zeevaert R, de Vos R, Demaerel P, Brams M, Jaeken J, Fransen M, Cassiman D
J Med Genet 2008 Jun;45(6):376-83. Epub 2008 Feb 19 doi: 10.1136/jmg.2007.056697. PMID: 18285423
Halonen P, Salo MK, Schmiegelow K, Mäkipernaa A
Acta Paediatr 2003;92(1):37-42. doi: 10.1111/j.1651-2227.2003.tb00466.x. PMID: 12650297
Duran M, De Klerk JB, Wadman SK, Bruinvis L, Ketting D
J Inherit Metab Dis 1984;7 Suppl 1:48-51. doi: 10.1007/BF03047374. PMID: 6434845

Diagnosis

Li X, Ma R, Liu Y, Kang L, He R, Song J, Ren J, Li Y, Huang M, Men J, Yang Y
Clin Chim Acta 2020 Apr;503:218-222. Epub 2019 Nov 30 doi: 10.1016/j.cca.2019.11.034. PMID: 31794763
Rubio-Gozalbo ME, Bakker JA, Waterham HR, Wanders RJ
Mol Aspects Med 2004 Oct-Dec;25(5-6):521-32. doi: 10.1016/j.mam.2004.06.007. PMID: 15363639
Shimizu N, Yamaguchi S, Orii T
Acta Paediatr Jpn 1994 Apr;36(2):139-45. doi: 10.1111/j.1442-200x.1994.tb03149.x. PMID: 8203256
Duran M, De Klerk JB, Wadman SK, Bruinvis L, Ketting D
J Inherit Metab Dis 1984;7 Suppl 1:48-51. doi: 10.1007/BF03047374. PMID: 6434845
Gregersen N, Kølvraa S, Mortensen PB, Rasmussen K
Scand J Clin Lab Invest Suppl 1982;161:15-27. doi: 10.3109/00365518209168396. PMID: 6959231

Therapy

Iacobazzi V, Pasquali M, Singh R, Matern D, Rinaldo P, Amat di San Filippo C, Palmieri F, Longo N
Am J Med Genet A 2004 Apr 15;126A(2):150-5. doi: 10.1002/ajmg.a.20573. PMID: 15057979
Halonen P, Salo MK, Schmiegelow K, Mäkipernaa A
Acta Paediatr 2003;92(1):37-42. doi: 10.1111/j.1651-2227.2003.tb00466.x. PMID: 12650297
Tserng KY, Griffin RL, Kerr DS
Metabolism 1996 Feb;45(2):162-7. doi: 10.1016/s0026-0495(96)90047-5. PMID: 8596483
Henderson MJ, Dear PR
Arch Dis Child 1986 Jun;61(6):610-1. doi: 10.1136/adc.61.6.610. PMID: 3729533Free PMC Article
Gregersen N, Kølvraa S, Mortensen PB, Rasmussen K
Scand J Clin Lab Invest Suppl 1982;161:15-27. doi: 10.3109/00365518209168396. PMID: 6959231

Prognosis

Li X, Ma R, Liu Y, Kang L, He R, Song J, Ren J, Li Y, Huang M, Men J, Yang Y
Clin Chim Acta 2020 Apr;503:218-222. Epub 2019 Nov 30 doi: 10.1016/j.cca.2019.11.034. PMID: 31794763
Desbats MA, Vetro A, Limongelli I, Lunardi G, Casarin A, Doimo M, Spinazzi M, Angelini C, Cenacchi G, Burlina A, Rodriguez Hernandez MA, Chiandetti L, Clementi M, Trevisson E, Navas P, Zuffardi O, Salviati L
Eur J Hum Genet 2015 Sep;23(9):1254-8. Epub 2015 Jan 7 doi: 10.1038/ejhg.2014.277. PMID: 25564041Free PMC Article
Yamaguchi S, Iga M, Kimura M, Suzuki Y, Shimozawa N, Fukao T, Kondo N, Tazawa Y, Orii T
J Chromatogr B Biomed Sci Appl 2001 Jul 5;758(1):81-6. doi: 10.1016/s0378-4347(01)00102-5. PMID: 11482738
Pons R, Roig M, Riudor E, Ribes A, Briones P, Ortigosa L, Baldellou A, Gil-Gibernau J, Olesti M, Navarro C, Wanders RJ
Pediatr Neurol 1996 Apr;14(3):236-43. doi: 10.1016/0887-8994(96)00021-5. PMID: 8736409
Gregersen N, Kølvraa S, Mortensen PB, Rasmussen K
Scand J Clin Lab Invest Suppl 1982;161:15-27. doi: 10.3109/00365518209168396. PMID: 6959231

Clinical prediction guides

Rubio-Gozalbo ME, Bakker JA, Waterham HR, Wanders RJ
Mol Aspects Med 2004 Oct-Dec;25(5-6):521-32. doi: 10.1016/j.mam.2004.06.007. PMID: 15363639
Yamaguchi S, Iga M, Kimura M, Suzuki Y, Shimozawa N, Fukao T, Kondo N, Tazawa Y, Orii T
J Chromatogr B Biomed Sci Appl 2001 Jul 5;758(1):81-6. doi: 10.1016/s0378-4347(01)00102-5. PMID: 11482738
Kurtz DM, Rinaldo P, Rhead WJ, Tian L, Millington DS, Vockley J, Hamm DA, Brix AE, Lindsey JR, Pinkert CA, O'Brien WE, Wood PA
Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15592-7. doi: 10.1073/pnas.95.26.15592. PMID: 9861014Free PMC Article
Tserng KY, Jin SJ, Kerr DS, Hoppel CL
J Lipid Res 1990 May;31(5):763-71. PMID: 2380628
Henderson MJ, Dear PR
Arch Dis Child 1986 Jun;61(6):610-1. doi: 10.1136/adc.61.6.610. PMID: 3729533Free PMC Article

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