Endocrine Abstracts

MCAD deficiency, the most prevalent disorder in fatty acid β-oxidation, typically presents with hypoketotic hypoglycemia, neuromuscular issues, and arrhythmias. This report details the case of a one-year and nine-month-old boy with normal development and no significant medical history, who experienced a generalized tonic-clonic seizure linked to hypoglycemia (random blood sugar 2.1 mmol/l). Further inquiry revealed the seizure occurred after prolonged fasting upon waking from sleep, accompanied by fever, upper respiratory symptoms, and poor oral intake for two days. The child’s evaluation suggested hypoketotic hypoglycemia, elevated triglycerides (385), and increased levels of specific acids in the urine, indicative of MCAD deficiency. Additionally, the child displayed hypocalcemia (ionised calcium-0.97 mmol/l)and elevated phosphorus(1.9 mmol/l) levels, with low intact parathyroid hormone (9 pmol/l) levels, implying a connection between MCAD deficiency and primary hypoparathyroidism. Despite negative results for adrenal and parathyroid autoantibodies, and the absence of autoimmune diseases or mucocutaneous candidiasis, primary hypoparathyroidism was suspected to be related to MCAD deficiency. Treatment included calcium carbonate supplements, calcitriol, and carnitine. Subsequent clinical evaluation revealed a defect in the ACADM gene, further supporting the diagnosis of MCAD deficiency. The ACADM gene is on chromosome 1, and MCAD deficiency is inherited as a recessive trait. The vast majority of patients with MCAD deficiency have a single common missense mutation which changes a lysine residue to glutamate. The mutated amino acid is far removed from the catalytic site of the enzyme but appears to make the protein unstable by interfering with intramitochondrial folding and assembly of the nascent peptide. Preventing this misfolding offers an opportunity for development of new therapeutic agents for MCAD deficiency. This case underscores the rare association between MCAD deficiency and primary hypoparathyroidism, emphasizing the importance of regular monitoring of calcium and phosphorus levels due to the potentially life-threatening nature of hypoparathyroidism. Further research is crucial to fully understand this complex association and its implications for patient management and treatment strategies.