Acyl-CoA dehydrogenase, medium chain (MCAD) deficiency is a congenital metabolic disorder that affects the mitochondrial fatty acid beta-oxidation pathway. Fatty acid oxidation, which fuels hepatic ketogenesis, is an essential process that converts certain fats into energy, particularly when carbohydrates are scarce. In hepatic cells, ketogenesis is the major source of energy after the depletion of hepatic glycogen, during prolonged fasting, and periods of high energy demands. Several enzymes work in a step-wise fashion during fatty acid oxidation. Due to defects in the ACADM gene, patients with MCAD deficiency have inadequate levels of medium-chain acyl-CoA dehydrogenase enzyme required for metabolizing a group of fats called medium-chain fatty acids. This results in the accumulation of medium-chain fatty acids in various tissues causing serious complications.
MCAD deficiency has an early onset and it is characterized by hypoketotic hypoglycemia, vomiting, and lethargy triggered by fasting or certain viral infections. In addition, serious complications can also be associated with MCAD deficiency such as seizures, breathing difficulties, liver problems, brain damage, coma, and sudden unexpected death.
Based on the data collected through newborn screening done randomly in 1000 newborns during a period of two years in Bahrain, Al Arrayed et al. (1999) reported 10 abnormal cases (incidence 1%). Deficiency of acyl-CoA dehydrogenase medium-chain was observed among this study group.
[Al Arrayed SS, Al Jishi E, Abbasi A, Rashed MS, Ozand PT. Newborn screening by using mass spectrometry. Bahrain Med Bull. 1999; 21(4)]
Ramadan et al. (2005) reported the first case of MCAD deficiency from Kuwait. The patient was a previously healthy 2-year old Non-Kuwaiti Arab girl, born to consanguineous parents, who was found unarousable one morning. At the hospital she was given a Glasgow Coma Scale of six and she developed a brief tonic-clonic seizure. Her liver was found to be enlarged and she was hypotonic. Urine was found to be negative for ketones, suggesting an inborn error of fatty acid oxidation. Acylcarnitine results confirmed the diagnosis of MCAD deficiency. She was put on a low-fat, high-carb diet, with an instruction to the parents not to let her fast longer than 8-10 hours. She was discharged on a daily dose of L-carnitine. Upon follow-up, the girl was found to be doing well at the age of 3.5 years, with normal growth, no hepatomegaly, and normal neurodevelopment. Her three siblings were tested for MCAD deficiency and were found to be normal.
[Ramadan DG, Al-Sharkawy I, Al-Ruqum FA. Hypoglycemic coma in a young girl: First case of medium chain acyl coA dehydrogenase (MCAD) deficiency identified in Kuwait. Kuwait Med J. 2005; 37(1):50-3.]
In 2003, the Hamad Medical Corporation, in partnership with the University Children's Hospital of Heidelberg built a comprehensive newborn screening program. Between December 2003 and July 2006, Lindner et al. (2007) investigated 25,214 neonates born in Qatar for inborn errors of metabolism and endocrine disorders. Six neonates were diagnosed with MCAD deficiency. The high frequency of this disorder in Qatar was a completely unexpected finding.
Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Fatty acid oxidation disorders were diagnosed in 18/248 patients (7%) through uncovering the deficiency of relevant enzymes. Among them, two cases from a single family were found to have MCAD deficiency. The estimated incidence of this condition is 1 in 100,000 live births. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.
Al-Shamsi et al. (2014) calculated the prevalence of MCAD deficiencyto be less than 0.98 per 100,000 live births.