Skip to Main Content

Introduction

The disorder affects approximately 1 in 35,000 to 50,000 newborns. It is caused by mutations or variants in the ACADS (Acyl-CoA Dehydrogenase, C-2 to C-3 Short Chain) gene, which has been mapped to chromosome 12q24.31. Inheritance is autosomal recessive. SCAD, a mitochondrial enzyme, initiates the cycle of β-oxidation for short-chain fatty acids (2-6 carbons atoms, although this definitions appear to be quite variable) by catalyzing their dehydrogenation with a chain-length substrate specificity ranging from C4 to C6. However, since SCAD is only required for the short-chain fatty acids in the β-oxidation cycle, gluconeogenetic and ketogenic capacity from the preceding steps of fatty acid oxidation may be sufficient to cover the basic cellular energy requirements. Potentially overlapping substrate specificity with medium-chain acyl-CoA dehydrogenase (MCAD) may help compensate for decreased SCAD activity. Since the preferred substrate for SCAD is butyryl-CoA, SCADD results in elevated levels of butyryl-CoA, which is then metabolized to butyrylcarnitine, butyrylglycine, methylsuccinyl-CoA and ethylmalonic, acid in body tissues and fluids with characteristic aciduria. SCADD is typically suspected in the presence of abnormal levels of these metabolites in blood, urine, and tissues. However, it appears that the enzyme defect per se does not necessarily lead to manifestation of the disease and that SCAD dysfunction in some patients may present under very adverse physiologic conditions only such as illness, fasting, and stress with an extremely heterogeneous spectrum of clinical symptoms. In a study of 114 patients, only 25% showed symptoms on day one of life, while 61% became symptomatic during the first year of life, and only 4% were diagnosed after 10 years of age. The most common symptoms detected were developmental and speech delay, seizures (both most likely secondary to the accumulation of toxic metabolites in the brain), hypoglycemic encephalopathy, hypotonia, dysmorphic features (microcephaly, narrow maxilla with high-arched palate, fish mouth, facial muscle weakness), optic atrophy, feeding difficulties (with gastroesophageal reflux), failure to thrive, and lethargy. Other, less frequent findings were scoliosis, respiratory distress (often due to severe and recurrent pulmonary infections as a consequence of hypotonia), myopathy (reported as multiminicore disease or as a lipid myopathy with severe intracellular vacuolar deposits of lipids and myofibrillar disruption), cardiomyopathy (one case repot of biatrial hypertrophy and left-ventricular dysfunction), and hepatic steatosis (at least in part due to accumulation of excessive amounts of fatty acids). However, for reasons not fully elucidated, yet, the clinical features in SCADD are frequently nonspecific, highly variable and often different from those seen in other types of fatty acid oxidation defects. Most individuals with SCADD are asymptomatic, hence no generally accepted recommendations regarding diet or use of carnitine and/or riboflavin (vitamin B2) supplementation exist. The risk for episodes of metabolic decompensation still exists though, so it seems sensible to prevent dehydration, metabolic acidosis, and hypoglycemia during intercurrent illnesses, fasting, or stress.

Precautions before anesthesia

Whenever possible, touch base with a metabolic specialist to discuss the best approach to these patients. ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.