A complication of pregnancy, HELLP Syndrome (hemolysis, elevated liver enzymes, and low platelets), has been described in women carrying a fetus affected with LCHAD deficiency.
Newborn screening using tandem mass spectrometry of a dried blood spot identifies elevated levels of several long chain hydroxyacylcarnitines (C16-OH, C16:1-OH, C18-OH, C18:1-OH and C16-OH/C16 is also found to be an informative ratio). Biochemical testing of blood and urine for carnitine, acylcarnitines, acylglycines, and organic acids is diagnostic for this disorder. Dicarboxylic and hydroxydicarboxylic acids are usually found with urine organic acid analysis, but may be “normal” when the patient is not acutely ill. Analysis of LCHAD activity in fibroblasts can reveal affected individuals compared to heterozygous carrier and normal fibroblast lines. LCHAD activity should be assayed after antibody precipitation of SCHAD activity, due to the overlap in substrate recognition.
LCHAD patients have a common mutation (1528G>C) in the -subunit of mitochondrial trifunctional protein. Detection of mutations in the DNA of affected individuals allows for confirmation of biochemical test results and accurate detection of asymptomatic carriers among other family members. Prenatal diagnosis is possible by enzyme assay of cultured amniocytes or by in vitro probe of the β-oxidation pathway. DNA analysis can also be used for prenatal diagnosis of affected fetuses in at-risk pregnancies when both parents carry a known mutation.
Fundamental to the medical management of LCHAD is the avoidance of fasting, particularly during periods of high metabolic stress, such as illness. Overnight fasts should last no longer that twelve hours and infants should receive late evening feedings to reduce this period. The addition of food-grade uncooked cornstarch mixed in liquid at bedtime has helped some infants decrease the frequency of morning hypoglycemia. A diet high in natural fat should be avoided. Medium-chain triglyceride supplementation bypasses the metabolic block and provides safe calories. Supplementation with oral L-Carnitine has not been shown to be beneficial in avoiding or ameliorating clinical symptoms.