A different perspective into clinical symptoms in CPT I deficiency

Mehmet Cihan Balci; Meryem Karaca; Arzu Selamioglu; Huseyin Kutay Korbeyli; Asli Durmus; Belkis Ak; Tugba Kozanoglu; Gulden Fatma Gokcay

doi:10.1016/j.ymgmr.2023.101032

A different perspective into clinical symptoms in CPT I deficiency

Mol Genet Metab Rep. 2023 Nov 30:38:101032. doi: 10.1016/j.ymgmr.2023.101032. eCollection 2024 Mar.

Authors

Mehmet Cihan Balci¹, Meryem Karaca¹, Arzu Selamioglu¹, Huseyin Kutay Korbeyli¹, Asli Durmus¹, Belkis Ak¹, Tugba Kozanoglu¹, Gulden Fatma Gokcay¹

Affiliation

¹ Division of Nutrition and Metabolism, Istanbul Medical Faculty Children's Hospital, Istanbul University, Istanbul, Turkey.

Abstract

Carnitine palmitoyltransferase I (CPT I) deficiency is an autosomal recessive disorder causing long-chain fatty acid oxidation defect, characterized by metabolic decompensation episodes accompanied by hypoketotic hypoglycemia, hepatomegaly, seizures, renal tubular acidosis, and hyperammonemia. The aim of this study was to investigate the neurological symptoms in CPT I deficiency and different outcomes with respect to predisposing factors for sequela and to draw attention to the neurological impairment that may develop during the course of the disease. The retrospective study reviewed clinical characteristics of 14 patients. Mean follow-up period was 10.3 ± 4.7 (range: 8 months-18.6 years; median: 10 years) years. Three patients were diagnosed with newborn screening. In the symptomatic group (n = 12) most common presenting symptoms were psychomotor retardation (n = 6), seizures (n = 5), encephalopathy (n = 5), dystonia (n = 1), Reye-like syndrome (n = 5), muscle weakness (n = 3), and autism (n = 1). Neurologic findings detected in the follow-up period included speech disorder (n = 9), abnormal cranial MRI findings (n = 5), neuropathy (n = 1), and attention deficit hyperactivity disorder (n = 1). Speech disorders collectively included delayed expressive language development, speech articulation disorder, speech delay, stuttering, and specific speech difficulties. After starting treatment for CPT I deficiency, speech disorders improved in 3 patients. Our findings confirmed that the clinical manifestations of CPT I deficiency is wider than previously thought, causing specific neurologic dysfunction, mainly speech disorders at a large scale, that were unexpected in a fatty acid oxidation disorder. We suggest that early diagnosis and treatment is the key factor to prevent neurologic sequelae while an extensive neurological evaluation is essential in patients with CPT I deficiency both at the time of diagnosis and during the follow-up period.

Keywords: Carnitine palmitoyltransferase I deficiency; Fatty acids; Language development disorders; Neurologic manifestations; Reye-like syndrome; Speech disorders.