Diagnosis of Fatty Acid Oxidation Disorders: Experience at Quest Diagnostics Nichols Institute Biochemical Genetics Laboratory

Sharma R, Tanpaiboon P, Salazar D, Bonilla-Guerrero R, and Lacbawan, FL.

Biochemical Genetics Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, CA 92690.

Background: Fatty acid oxidation disorders are a group of autosomal recessive enzyme defects that lead to disruption of the mitochondrial beta-oxidation cycle. Although individually rare, the combined incidence of this group of disorders is significant, especially given that many infants identified through newborn screening might never have developed clinical symptoms and would have remained undiagnosed. Fasting hypoglycemia, without accompanying ketosis, is a classic finding in a majority of these disorders. There is variable age of onset and variable clinical presentation affecting multiple organ systems, although heart and muscle are disproportionately affected. Many of these disorders can now be detected through expanded tandem mass spectrometry-based newborn screening. Because of the overlap in clinical features among this group of defects, diagnosis must incorporate confirmatory biochemical and/or molecular testing. Early recognition and diagnosis of these disorders is critical, as avoidance of fasting and/or initiation of dietary therapy is sufficient to prevent irreversible damage in many cases.  With early diagnosis and treatment, most babies with these disorders can lead normal, healthy lives. In the absence of treatment, serious sequelae, and even death, can result.

Study Goal: The goal of the current investigation was to examine the prevalence of different types of fatty acid oxidation disorders in patients diagnosed at Quest Diagnostics Nichols Institute.

Results: Out of 1,456 patients that were diagnosed, primarily by acylcarnitine analysis in our laboratory, medium-chain acyl-CoA dehydrogenase deficiency (MCAD) was the most common diagnosis [n=68 (newborn – 53 years), 47% of positives], very long-chain acyl-CoA dehydrogenase deficiency (VLCAD) [n=228 (newborn – 65 years), 15.7% of positives], short-chain acyl-CoA dehydrogenase deficiency (SCAD) [n=283 (newborn – 65 years), 19.4% of positives], long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency/trifunctional protein deficiency (LCHAD/TFP) [n=80 (newborn – 66 years), 5.5% of positives], carnitine palmitoyltransferase II (CPT-II) deficiency [n=82 (newborn – 67 years), 6% of positives], carnitine transporter defect [n=89 (newborn – 48 years), 6 % of positives], and carnitine palmitoyltransferase I (CPT-I) deficiency [n=10 (newborn – 31 years), 0.7% of positives].

Conclusions: For each of the seven disorders analyzed in our study, the age distribution of patients ranged from the neonatal period to late adulthood. While the majority of patients diagnosed with these disorders are expected to be infants with positive screening results or with classical early childhood presentations, the many adult patients identified in our study underscore the importance of biochemical genetic testing in this patient population. The clinical features of late onset variants of fatty acid oxidation defects may be significantly different from the classical features associated with the underlying disorder, which, along with the patient’s age, could lead to a significant delay in diagnosis if these disorders are not considered in the differential diagnosis.

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