Clinical Guidance

No consistent genotype-phenotype correlations have been observed. However, data have suggested a correlation between urinary levels of biomarkers (ethylmalonic acid and methylsuccinic acid) and presence of biallelic SCADD-related ACADS variants versus compound heterozygosity for one SCADD-related variant and one of the two common (benign) variants ( or ) . Individuals with biallelic common (benign) variants (c.511CT or c.625GA) are highly prevalent in the general population such that these findings cannot represent a significant risk for clinical disease .

Source: GeneReviews — "Short-Chain Acyl-CoA Dehydrogenase Deficiency"

Diagnostic Criteria

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a biochemical phenotype without clinical manifestations.

Suggestive Findings

SCADD should be suspected in an infant with an OR in a proband with identified in the process of evaluation for a possible inborn error of metabolism.

Infant with Out-of-Range NBS Result

NBS for SCADD is primarily based on the use of dried blood spots collected between 24 and 72 hours after birth to quantify C4 acylcarnitine concentration (butyrylcarnitine is elevated in SCADD) by tandem mass spectrometry. In the United States, most NBS laboratories determine their own cutoff levels for test results that are considered to be out of range. For information on NBS by state in the US, see www.newbornscreening.hrsa.gov/your-state.

Source: GeneReviews — "Short-Chain Acyl-CoA Dehydrogenase Deficiency"

Differential Diagnosis

Genetic disorders associated with increased butyrylcarnitine concentration (and/or other C4 acylcarnitines) in plasma and/or increased ethylmalonic acid (EMA) concentration in urine to consider in the differential diagnosis of short-chain acyl-CoA dehydrogenase deficiency (SCADD) include those listed in . Note: It is becoming increasingly apparent that elevation of C4 carnitine in blood with increased EMA in urine is frequently unrelated to SCADD. Table 2. Genes of Interest in the Differential Diagnosis of Short-Chain Acyl-CoA Dehydrogenase Deficiency

Management Guidelines

No clinical practice guidelines for short-chain acyl CoA dehydrogenase deficiency (SCADD) have been published.

Evaluations Following Initial Diagnosis

Once a molecular diagnosis of SCADD deficiency is made, there is no need for additional clinical evaluation.

Treatment of Manifestations

Since SCADD is now viewed as a biochemical phenotype rather than a disease, there is no need for treatment. Given the paucity of research, especially long-term follow-up studies, enrollment in a long-term follow-up study with a biochemical geneticist can be offered.

Surveillance

Longitudinal follow up of individuals with SCADD on a research basis, including annual visits to a metabolic clinic to assess growth, development, and nutritional status (protein and iron stores, concentration of red blood cell or plasma essential fatty acids, and plasma carnitine concentration), could be helpful to more clearly define unrecognized phenotypes as individuals age.

Evaluation of Relatives at Risk

See for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Short-Chain Acyl-CoA Dehydrogenase Deficiency"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Short-Chain Acyl-CoA Dehydrogenase Deficiency"

Surveillance Guidelines

Longitudinal follow up of individuals with SCADD on a research basis, including annual visits to a metabolic clinic to assess growth, development, and nutritional status (protein and iron stores, concentration of red blood cell or plasma essential fatty acids, and plasma carnitine concentration), could be helpful to more clearly define unrecognized phenotypes as individuals age.

Source: GeneReviews — "Short-Chain Acyl-CoA Dehydrogenase Deficiency"