A Rare Case of Short-Chain Acyl-COA Dehydrogenase Deficiency: The Apparent Rarity of the Disorder Results in Under Diagnosis

Abstract

Short-chain acyl-CoA dehydrogenase (ACAD) deficiency is an extremely rare inherited mitochondrial disorder of fat metabolism. This belongs to a group of diseases known as fatty acid oxidation disorders. Screening programmes have provided evidence that all the fatty acid oxidation disorders combined are among the most common inborn errors of metabolism. Mitochondrial beta oxidation of fatty acids is an essential energy producing pathway. It is a particularly important pathway during prolonged periods of starvation and during periods of reduced caloric intake due to gastrointestinal illness or increased energy expenditure during febrile illness. The most common presentation is an acute episode of life threatening coma and hypoglycemia induced by a period of fasting due to defective hepatic ketogenesis. Here, the case of a 4 month old female patient who had seizures since the third day of her birth and persistent hypoglycemia is described. She was born to parents of second degree consanguinity after 10 years of infertility treatment. There was history of delayed cry after birth. Metabolic screening for TSH, galactosemia, 17-OHP, G6PD, cystic fibrosis, biotinidase were normal. Tandem mass spectrometric (TMS) screening for blood amino acids, organic acids, fatty acids showed elevated butyryl carnitine (C4) as 3.40 lmol/L (normal \2.00 lmol/L), hexanoyl carnitine (C6) as 0.92 lmol/L (normal \0.72 lmol/L), C4/C3 as 2.93 lmol/L (normal \1.18 lmol/L). The child was started immediately on carnitor syrup (carnitine) 1/2 ml twice daily. Limitation of fasting stress and dietary fat was advised. Baby responded well by gaining weight and seizures were controlled. Until now, less than 25 patients have been reported worldwide. The limited number of patients diagnosed until now is due to the rarity of the disorder resulting in under diagnosis.

Mitochondrial epilepsy in pediatric and adult patients

“…Affected compounds in these patients include, for example, the hydroxysteroid (17beta) dehydrogenase 10 , the lipoic acid synthetase , or the aconitase, a Krebs cycle enzyme, the latter resulting in infancy‐onset hypotonia, athetosis, and ophthalmologic disease in addition to epilepsy . Epilepsy may be also a part of the phenotype in beta‐oxidation disorders, such as in short‐chain acyl‐CoA dehydrogenase deficiency, of which the most common presentation is coma due to hypoglycemia after fasting starting in early infancy .…”

“…In a single patient with AHS drug‐refractory status epilepticus could be terminated only by functional hemispherectomy . In patients with mitochondrial depletion‐syndrome due to MPV‐17 mutations or short‐chain acyl‐CoA dehydrogenase deficiency, prolonged fasting must be avoided .…”

Genome scale metabolic network modelling for metabolic profile predictions

“…Carnitine also plays a role in the stabilisation of CoA and acetyl-CoA levels, as well as energy production by taking part in a rate controlling step in mitochondrial oxidation of long-chain fatty acids [ 27 ]. Medically, L-carnitine is used as treatment in some cases of ACADS deficiency (also known as SCAD deficiency (short chain acyl-CoA dehydrogenase)) [ 28 ]. Regarding the highly ranked amino acids, an adjacent enzyme Isobutyryl CoA Dehydrogenase (IBD), which is coded by ACAD8 and shares GPRs with ACADS, has been shown to be involved in valine metabolism [ 29 , 30 ].…”

A case report of short-chain acyl-CoA dehydrogenase deficiency (SCADD)

“…The disorder has been reported in infants, children and adults ( 7 , 17 ). Most symptomatic cases of SCADD have been diagnosed due to large diagnostic work-up on children with non-specific findings such as development delay, failure to thrive and myopathy ( 18 ). However, the clinical relevance of SCADD is questionable and still under discussion.…”