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Succinyl-CoA:3-ketoacid CoA transferase deficiency
Succinyl-CoA:3-ketoacid CoA transferase deficiency (SCOTD) is a defect in ketone body utilization characterized by severe, potentially fatal intermittent episodes of ketoacidosis.
- OXCT1 deficiency
- SCOT deficiency
- Succinyl-CoA acetoacetate transferase deficiency
- Succinyl-CoA:3-oxoacid CoA transferase deficiency
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: E71.3
- OMIM: 245050
- UMLS: C0342792
- MeSH: -
- GARD: 4774
- MedDRA: -
Prevalence of SCOTD is unknown, 33 cases have been reported to date.
SCOTD patients present with a first ketoacidotic attack as a newborn (2-4 days), or later between 6-20 months of age. Initial episodes are often severe, and further episodes may be triggered by metabolic stress, infection or extended periods of fasting. Symptoms include tachypnea, vomiting, lethargy,hypotonia, and ,in severe cases, coma. Episode intensity and frequency is variable and severe attacks are potentially fatal. Patients are generally healthy and develop normally between episodes, but infants may present with failure to thrive and poor feeding prior to diagnosis. Cardiomegaly has developed in two cases and may lead to congestive heart failure.
SCOTD is caused by mutations in the OXCT1 gene (5p13) that encodes the mitochondrial enzyme essential for ketone body metabolism in all extrahepatic tissue: succinyl CoA:3-ketoacid CoA transferase. Over 20 different mutations to OXCT1 have been identified, all leading to the accumulation of ketone bodies and ketoacidosis during periods of catabolic stress. Partial loss-of-function mutations have been identified that also lead to severe ketoacidosis, but without permanent ketosis.
Permanent ketosis or persistent ketouria are pathognomic features of SCOTD, however, some mild cases may not present with these signs. Patients display metabolic acidosis during crises and both serum and urinalysis reveal high levels of ketones, pH levels between 6.8 and 7.12 and HCO3 levels between 3-8 mmol/l may be observed. There is no characteristic organic acid or acylcarnitine profile. The ratio of free fatty acids to total ketone bodies becomes less than 0.3 during a short fast and this may lead one to suspect SCOTD. Enzyme activity assays using fibroblasts, lymphocytes or platelets reveal a lack, or great reduction, of functional succinylCoA : 3-ketoacid CoA transferase.
Differential diagnoses include physiological ketosis and ketoacidosis due to beta-ketothiolase deficiency (see this term).
Prenatal diagnosis by enzyme activity assays is possible using cultured amniocytes.
SCOTD is inherited in an autosomal recessive manner; siblings of affected individuals whose parents do not have the syndrome will therefore have a 25% chance of having the disorder.
Management and treatment
Ketoacidotic crises must be treated immediately with intravenous fluid therapy including glucose and 50-100 mmol sodium bicarbonate until pH has returned to normal. Patients must avoid prolonged fasting. A fat-rich diet which induces ketogenesis should be avoided. Mild protein restriction may be applicable but not always necessary. Home monitoring of urinary ketones helps parents to follow the patient's condition. Carbohydrate-rich food or drink should immediately be provided if ketone levels are higher than usual. If patients become weak or vomit, intravenous glucose infusions should be considered.
Normal growth and development is expected when proper treatment and diet is followed to prevent the recurrence of severe ketoacidotic attacks. Frequency of ketoacidotic episodes decreases after the age of 10.