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Episodic metabolic acidosis

MedGen UID:
349179
Concept ID:
C1859516
Finding
Synonyms: Metabolic acidosis, episodic; Recurrent episodes of acidosis
 
HPO: HP:0004911

Definition

Repeated transient episodes of metabolic acidosis, that is, of the buildup of acid or depletion of base due to accumulation of metabolic acids. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVEpisodic metabolic acidosis

Conditions with this feature

3-methylcrotonyl-CoA carboxylase 1 deficiency
MedGen UID:
78691
Concept ID:
C0268600
Disease or Syndrome
3-Methylcrotonylglycinuria is an autosomal recessive disorder of leucine catabolism. The clinical phenotype is highly variable, ranging from neonatal onset with severe neurologic involvement to asymptomatic adults. There is a characteristic organic aciduria with massive excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, usually in combination with a severe secondary carnitine deficiency. MCC activity in extracts of cultured fibroblasts of patients is usually less than 2% of control (summary by Baumgartner et al., 2001). Also see 3-methylcrotonylglycinuria II (MCC2D; 210210), caused by mutation in the beta subunit of 3-methylcrotonyl-CoA carboxylase (MCCC2; 609014).
Deficiency of butyryl-CoA dehydrogenase
MedGen UID:
90998
Concept ID:
C0342783
Disease or Syndrome
Most infants with short-chain acyl-CoA dehydrogenase deficiency (SCADD) identified through newborn screening programs have remained well, and asymptomatic relatives who meet diagnostic criteria are reported. Thus, SCADD is now viewed as a biochemical phenotype rather than a disease. A broad range of clinical findings was originally reported in those with confirmed SCADD, including severe dysmorphic facial features, feeding difficulties / failure to thrive, metabolic acidosis, ketotic hypoglycemia, lethargy, developmental delay, seizures, hypotonia, dystonia, and myopathy. However, individuals with no symptoms were also reported. In a large series of affected individuals detected on metabolic evaluation for developmental delay, 20% had failure to thrive, feeding difficulties, and hypotonia; 22% had seizures; and 30% had hypotonia without seizures. In contrast, the majority of infants with SCADD have been detected by expanded newborn screening, and the great majority of these infants remain asymptomatic. As with other fatty acid oxidation deficiencies, characteristic biochemical findings of SCADD may be absent except during times of physiologic stress such as fasting and illness. A diagnosis of SCADD based on clinical findings should not preclude additional testing to look for other causes.
Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency
MedGen UID:
344424
Concept ID:
C1855114
Disease or Syndrome
For this GeneReview, the term "isolated methylmalonic acidemia" refers to a group of inborn errors of metabolism associated with elevated methylmalonic acid (MMA) concentration in the blood and urine that result from the failure to isomerize (convert) methylmalonyl-coenzyme A (CoA) into succinyl-CoA during propionyl-CoA metabolism in the mitochondrial matrix, without hyperhomocysteinemia or homocystinuria, hypomethioninemia, or variations in other metabolites, such as malonic acid. Isolated MMA is caused by complete or partial deficiency of the enzyme methylmalonyl-CoA mutase (mut0 enzymatic subtype or mut– enzymatic subtype, respectively), a defect in the transport or synthesis of its cofactor, 5-deoxy-adenosyl-cobalamin (cblA, cblB, or cblD-MMA), or deficiency of the enzyme methylmalonyl-CoA epimerase. Prior to the advent of newborn screening, common phenotypes included: Infantile/non-B12-responsive form (mut0 enzymatic subtype, cblB), the most common phenotype, associated with infantile-onset lethargy, tachypnea, hypothermia, vomiting, and dehydration on initiation of protein-containing feeds. Without appropriate treatment, the infantile/non-B12-responsive phenotype could rapidly progress to coma due to hyperammonemic encephalopathy. Partially deficient or B12-responsive phenotypes (mut– enzymatic subtype, cblA, cblB [rare], cblD-MMA), in which symptoms occur in the first few months or years of life and are characterized by feeding problems, failure to thrive, hypotonia, and developmental delay marked by episodes of metabolic decompensation. Methylmalonyl-CoA epimerase deficiency, in which findings range from complete absence of symptoms to severe metabolic acidosis. Affected individuals can also develop ataxia, dysarthria, hypotonia, mild spastic paraparesis, and seizures. In those individuals diagnosed by newborn screening and treated from an early age, there appears to be decreased early mortality, less severe symptoms at diagnosis, favorable short-term neurodevelopmental outcome, and lower incidence of movement disorders and irreversible cerebral damage. However, secondary complications may still occur and can include intellectual disability, tubulointerstitial nephritis with progressive impairment of renal function, "metabolic stroke" (bilateral lacunar infarction of the basal ganglia during acute metabolic decompensation), pancreatitis, growth failure, functional immune impairment, bone marrow failure, optic nerve atrophy, arrhythmias and/or cardiomyopathy (dilated or hypertrophic), liver steatosis/fibrosis/cancer, and renal cancer.
Nephropathic cystinosis
MedGen UID:
419735
Concept ID:
C2931187
Disease or Syndrome
Cystinosis comprises three allelic phenotypes: Nephropathic cystinosis in untreated children is characterized by renal Fanconi syndrome, poor growth, hypophosphatemic/calcipenic rickets, impaired glomerular function resulting in complete glomerular failure, and accumulation of cystine in almost all cells, leading to cellular dysfunction with tissue and organ impairment. The typical untreated child has short stature, rickets, and photophobia. Failure to thrive is generally noticed after approximately age six months; signs of renal tubular Fanconi syndrome (polyuria, polydipsia, dehydration, and acidosis) appear as early as age six months; corneal crystals can be present before age one year and are always present after age 16 months. Prior to the use of renal transplantation and cystine-depleting therapy, the life span in nephropathic cystinosis was no longer than ten years. With these interventions, affected individuals can survive at least into the mid-forties or fifties with satisfactory quality of life. Intermediate cystinosis is characterized by all the typical manifestations of nephropathic cystinosis, but onset is at a later age. Renal glomerular failure occurs in all untreated affected individuals, usually between ages 15 and 25 years. The non-nephropathic (ocular) form of cystinosis is characterized clinically only by photophobia resulting from corneal cystine crystal accumulation.
Multiple mitochondrial dysfunctions syndrome 1
MedGen UID:
478062
Concept ID:
C3276432
Disease or Syndrome
Multiple mitochondrial dysfunctions syndrome is a severe autosomal recessive disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, lactic acidosis, and early death (summary by Seyda et al., 2001). Genetic Heterogeneity of Multiple Mitochondrial Dysfunctions Syndrome See also MMDS2 (614299), caused by mutation in the BOLA3 gene (613183) on chromosome 2p13; MMDS3 (615330), caused by mutation in the IBA57 gene (615316) on chromosome 1q42; MMDS4 (616370), caused by mutation in the ISCA2 gene (615317) on chromosome 14q24; MMDS5 (617613), caused by mutation in the ISCA1 gene (611006) on chromosome 9q21; MMDS6 (617954), caused by mutation in the PMPCB gene (603131) on chromosome 7q22; and MMDS7 (620423), caused by mutation in the GCSH gene (238330) on chromosome 16q23.

Professional guidelines

PubMed

Tetsuka S, Ogawa T, Hashimoto R, Kato H
Metab Brain Dis 2021 Dec;36(8):2181-2193. Epub 2021 Jun 12 doi: 10.1007/s11011-021-00772-x. PMID: 34118021
Barcelos I, Shadiack E, Ganetzky RD, Falk MJ
Curr Opin Pediatr 2020 Dec;32(6):707-718. doi: 10.1097/MOP.0000000000000954. PMID: 33105273Free PMC Article
El-Hattab AW, Adesina AM, Jones J, Scaglia F
Mol Genet Metab 2015 Sep-Oct;116(1-2):4-12. Epub 2015 Jun 15 doi: 10.1016/j.ymgme.2015.06.004. PMID: 26095523

Recent clinical studies

Etiology

Carrizales-Sepúlveda EF, Vera-Pineda R, Jiménez-Castillo RA, Violante-Cumpa JR, Flores-Ramírez R, Ordaz-Farías A
Am J Med Sci 2021 Jun;361(6):690-701. Epub 2020 Nov 26 doi: 10.1016/j.amjms.2020.11.030. PMID: 33941367
Kuppermann N, Ghetti S, Schunk JE, Stoner MJ, Rewers A, McManemy JK, Myers SR, Nigrovic LE, Garro A, Brown KM, Quayle KS, Trainor JL, Tzimenatos L, Bennett JE, DePiero AD, Kwok MY, Perry CS 3rd, Olsen CS, Casper TC, Dean JM, Glaser NS; PECARN DKA FLUID Study Group
N Engl J Med 2018 Jun 14;378(24):2275-2287. doi: 10.1056/NEJMoa1716816. PMID: 29897851Free PMC Article
Burke KR, Schumacher CA, Harpe SE
Pharmacotherapy 2017 Feb;37(2):187-194. Epub 2017 Jan 16 doi: 10.1002/phar.1881. PMID: 27931088
Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Gonzalez-Padilla DA
Cochrane Database Syst Rev 2016 Jan 21;2016(1):CD011281. doi: 10.1002/14651858.CD011281.pub2. PMID: 26798030Free PMC Article
Sibai BM, Viteri OA
Obstet Gynecol 2014 Jan;123(1):167-178. doi: 10.1097/AOG.0000000000000060. PMID: 24463678

Diagnosis

Eshkoli T, Barski L, Faingelernt Y, Jotkowitz A, Finkel-Oron A, Schwarzfuchs D
Eur J Obstet Gynecol Reprod Biol 2022 Feb;269:41-46. Epub 2021 Dec 21 doi: 10.1016/j.ejogrb.2021.12.011. PMID: 34968873
Carrizales-Sepúlveda EF, Vera-Pineda R, Jiménez-Castillo RA, Violante-Cumpa JR, Flores-Ramírez R, Ordaz-Farías A
Am J Med Sci 2021 Jun;361(6):690-701. Epub 2020 Nov 26 doi: 10.1016/j.amjms.2020.11.030. PMID: 33941367
Kuppermann N, Ghetti S, Schunk JE, Stoner MJ, Rewers A, McManemy JK, Myers SR, Nigrovic LE, Garro A, Brown KM, Quayle KS, Trainor JL, Tzimenatos L, Bennett JE, DePiero AD, Kwok MY, Perry CS 3rd, Olsen CS, Casper TC, Dean JM, Glaser NS; PECARN DKA FLUID Study Group
N Engl J Med 2018 Jun 14;378(24):2275-2287. doi: 10.1056/NEJMoa1716816. PMID: 29897851Free PMC Article
Burke KR, Schumacher CA, Harpe SE
Pharmacotherapy 2017 Feb;37(2):187-194. Epub 2017 Jan 16 doi: 10.1002/phar.1881. PMID: 27931088
Sibai BM, Viteri OA
Obstet Gynecol 2014 Jan;123(1):167-178. doi: 10.1097/AOG.0000000000000060. PMID: 24463678

Therapy

Kuppermann N, Ghetti S, Schunk JE, Stoner MJ, Rewers A, McManemy JK, Myers SR, Nigrovic LE, Garro A, Brown KM, Quayle KS, Trainor JL, Tzimenatos L, Bennett JE, DePiero AD, Kwok MY, Perry CS 3rd, Olsen CS, Casper TC, Dean JM, Glaser NS; PECARN DKA FLUID Study Group
N Engl J Med 2018 Jun 14;378(24):2275-2287. doi: 10.1056/NEJMoa1716816. PMID: 29897851Free PMC Article
Burke KR, Schumacher CA, Harpe SE
Pharmacotherapy 2017 Feb;37(2):187-194. Epub 2017 Jan 16 doi: 10.1002/phar.1881. PMID: 27931088
Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Gonzalez-Padilla DA
Cochrane Database Syst Rev 2016 Jan 21;2016(1):CD011281. doi: 10.1002/14651858.CD011281.pub2. PMID: 26798030Free PMC Article
El-Hattab AW, Adesina AM, Jones J, Scaglia F
Mol Genet Metab 2015 Sep-Oct;116(1-2):4-12. Epub 2015 Jun 15 doi: 10.1016/j.ymgme.2015.06.004. PMID: 26095523
Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB
Diabetes Care 2015 Sep;38(9):1687-93. Epub 2015 Jun 15 doi: 10.2337/dc15-0843. PMID: 26078479Free PMC Article

Prognosis

Lin Y, Wang J, Ren H, Ma X, Wang W, Zhao Y, Xu Z, Liu S, Wang W, Xu X, Wang B, Zhao D, Wang D, Li W, Liu F, Zhao Y, Lu J, Yan C, Ji K
J Neurol 2024 Feb;271(2):864-876. Epub 2023 Oct 17 doi: 10.1007/s00415-023-12005-5. PMID: 37847292
Trainor JL, Glaser NS, Tzimenatos L, Stoner MJ, Brown KM, McManemy JK, Schunk JE, Quayle KS, Nigrovic LE, Rewers A, Myers SR, Bennett JE, Kwok MY, Olsen CS, Casper TC, Ghetti S, Kuppermann N; Pediatric Emergency Care Applied Research Network (PECARN) FLUID Study Group
Ann Emerg Med 2023 Aug;82(2):167-178. Epub 2023 Apr 5 doi: 10.1016/j.annemergmed.2023.01.001. PMID: 37024382Free PMC Article
Alves CAPF, Zandifar A, Peterson JT, Tara SZ, Ganetzky R, Viaene AN, Andronikou S, Falk MJ, Vossough A, Goldstein AC
AJNR Am J Neuroradiol 2023 May;44(5):602-610. Epub 2023 Apr 6 doi: 10.3174/ajnr.A7837. PMID: 37024306Free PMC Article
Low JA
Baillieres Clin Obstet Gynaecol 1996 Jun;10(2):211-24. doi: 10.1016/s0950-3552(96)80034-4. PMID: 8836481
Gronert GA
Anesthesiology 1980 Nov;53(5):395-423. doi: 10.1097/00000542-198011000-00007. PMID: 6999950

Clinical prediction guides

Trainor JL, Glaser NS, Tzimenatos L, Stoner MJ, Brown KM, McManemy JK, Schunk JE, Quayle KS, Nigrovic LE, Rewers A, Myers SR, Bennett JE, Kwok MY, Olsen CS, Casper TC, Ghetti S, Kuppermann N; Pediatric Emergency Care Applied Research Network (PECARN) FLUID Study Group
Ann Emerg Med 2023 Aug;82(2):167-178. Epub 2023 Apr 5 doi: 10.1016/j.annemergmed.2023.01.001. PMID: 37024382Free PMC Article
Ng YS, Lax NZ, Blain AP, Erskine D, Baker MR, Polvikoski T, Thomas RH, Morris CM, Lai M, Whittaker RG, Gebbels A, Winder A, Hall J, Feeney C, Farrugia ME, Hirst C, Roberts M, Lawthom C, Chrysostomou A, Murphy K, Baird T, Maddison P, Duncan C, Poulton J, Nesbitt V, Hanna MG, Pitceathly RDS, Taylor RW, Blakely EL, Schaefer AM, Turnbull DM, McFarland R, Gorman GS
Brain 2022 Apr 18;145(2):542-554. doi: 10.1093/brain/awab353. PMID: 34927673Free PMC Article
Kuppermann N, Ghetti S, Schunk JE, Stoner MJ, Rewers A, McManemy JK, Myers SR, Nigrovic LE, Garro A, Brown KM, Quayle KS, Trainor JL, Tzimenatos L, Bennett JE, DePiero AD, Kwok MY, Perry CS 3rd, Olsen CS, Casper TC, Dean JM, Glaser NS; PECARN DKA FLUID Study Group
N Engl J Med 2018 Jun 14;378(24):2275-2287. doi: 10.1056/NEJMoa1716816. PMID: 29897851Free PMC Article
El-Hattab AW, Adesina AM, Jones J, Scaglia F
Mol Genet Metab 2015 Sep-Oct;116(1-2):4-12. Epub 2015 Jun 15 doi: 10.1016/j.ymgme.2015.06.004. PMID: 26095523
Gronert GA
Anesthesiology 1980 Nov;53(5):395-423. doi: 10.1097/00000542-198011000-00007. PMID: 6999950

Recent systematic reviews

Stefanetti RJ, Ng YS, Errington L, Blain AP, McFarland R, Gorman GS
Neurology 2022 Jun 7;98(23):e2318-e2328. Epub 2022 Apr 15 doi: 10.1212/WNL.0000000000200299. PMID: 35428733Free PMC Article
Pisani L, Astuto M, Prediletto I, Longhini F
Pulmonology 2019 Nov-Dec;25(6):348-354. Epub 2019 Oct 5 doi: 10.1016/j.pulmoe.2019.08.001. PMID: 31591056
Bianchetti DGAM, Amelio GS, Lava SAG, Bianchetti MG, Simonetti GD, Agostoni C, Fossali EF, Milani GP
Pediatr Nephrol 2018 Apr;33(4):673-681. Epub 2017 Dec 7 doi: 10.1007/s00467-017-3844-8. PMID: 29218437
Burke KR, Schumacher CA, Harpe SE
Pharmacotherapy 2017 Feb;37(2):187-194. Epub 2017 Jan 16 doi: 10.1002/phar.1881. PMID: 27931088
Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Gonzalez-Padilla DA
Cochrane Database Syst Rev 2016 Jan 21;2016(1):CD011281. doi: 10.1002/14651858.CD011281.pub2. PMID: 26798030Free PMC Article

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