“Disease is a consequence of chemical instability” -Archibald E. Garrod, 1908
Many autistic individuals share symptoms of other medical conditions. Indeed seizures in autism are common and often refractory to treatment. Metabolic conditions such as mitochondrial and folate disorders are also common and we have spoken about them in previous blogs (follow links in previously underlined terms). Other metabolic disorders (e.g., creatine, cholesterol, pyridoxine, biotine, carnitine) are believed to be associated to autism but their prevalence remains unknown. Treatment in these cases, e.g., ketogenic diet, may serve to treat the seizures but also to enhance mitochondrial function (Cheng et al., 2017). Some physicians now view autism as a multisystem disorder accompanied by metabolic and mitochondrial impairments that need proper assessment and treatment (Mumper and Bedell Cook, 2015). It is in this regard that early newborn screening for potential complications is of importance.
According to the Centers for Disease Control and Prevention: “Newborn screening identifies conditions that can affect a child’s long-term health or survival. Early detection, diagnosis, and intervention can prevent death or disability and enable children to reach their full potential. Each year, millions of babies in the U.S. are routinely screened, using a few drops of blood from the newborn’s heel, for certain genetic, endocrine, and metabolic disorders, and are also tested for hearing loss and critical congenital heart defects (CCHDs) prior to discharge from a hospital or birthing center”.
Metabolism is the sum total of all chemical reactions that occur within an organism. These reactions are usually facilitated (catalyzed) by proteins. When they are defined by a genetic defect the same tends to be recessive in origin. Newborn screening for metabolic disorders have been in place since 1965 as a result of knowledge gained regarding phenylketonuria (PKU). Since then, screening has expanded to include over 50 conditions. The variability of conditions present in each screening is determined by each state’s public health department. Usually these tests only identify individuals who may have a disorder so that further testing may determine whether a medical condition is truly present.
The main features in the clinical presentation of metabolic disorders tend to be a malfunction of the brain or encephalopathy (irritability, seizures, lethargy coma), liver dysfunction, and cardiac failure. Timing of symptom onset tends to be early in life, often before birth (while developing in the womb). A later presentation may follow a variable natural history as either acute recurrent attacks, chronic and progressive symptoms, or specific permanent adverse event on various organs or systems.
Laboratory testing relies primarily on a blood sample, measuring oxygen concentrations with a pulse oximeter, and a hearing screen. Basic testing (capable of being done in 30-60 minutes): finger stick blood glucose, arterial blood gases, urinalysis (ketones), complete blood count, live function tests, ammonia, electrolytes, lactate, and creatine kinase. Special testing may take longer for results to be known (24 to 48 hours): plasma: amino acids, acylcarnitine profile, total and free carnitine, urine (organic acids, orotic acid, ammino acids), cerebral spinal fluid.
Preliminary treatment for disorders of intoxication: Promote anabolism (increase glucose infusion, provide with fat infusion), remove toxins (ammonia scavenger agents, correct metabolic acidosis, carnitine supplementation, hemodialysis). For disorders of disturbed energy metabolism like acidosis treat with sodium bicarbonate, for lactic academia reduce glucose infusion, and provide sodium bicarbonate, and a trial of biotin, thiamin and riboflavin.
Although many studies have documented the presence of metabolic abnormalities in autistic individuals a single biomarker capable of being used for diagnosis or as a severity dependent measure of outcome has not been determined.
Cheng N, Rho JM, Masino SA. Metabolic dysfunction underlying auism spectrum disorder and potential treatment approaches. Front Mol Neurosci 10:34, 2017.
Mumper E, Bedell Cook S, Metabolic consideration in autism spectrum disorder. Natural Medicine Journal 7(2), 2015 (https://www.naturalmedicinejournal.com/journal/2015-02/metabolic-considerations-autism-spectrum-disorder)