A Case of Homozygous Disruption of P450 Side-Chain Cleavage (CYP11A1): Cerebral MRI and CSF Neurotransmitter Findings

Abstract

Mitochondrial cytochrome P450 side-chain cleavage enzyme (P450scc, CYP11A1) is the initiating enzyme of steroidogenesis and converts cholesterol to pregnenolone. Here we describe neurological, cerebral magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) findings in a patient with a homozygous disruption of P450scc. Free γ-aminobutyric acid (GABA) and glutamate levels were measured in the patient's CSF and control samples from 10 subjects by mean of high performance liquid chromatography with electrochemical detection. In the CSF, patient's free GABA levels were significantly reduced in comparison to control values. Cerebral MRI revealed multiple supratentorial located T2 lesions in the periventricular and peritrigonal white matter without gadolinium enhancement or diffusion restriction of lesions. Both MRI and CSF neurotransmitter findings in our patient with P450scc deficiency were comparable to those found in multiple sclerosis.

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“…P450scc is responsible for the initiation of steroidogenesis with the conversion of cholesterol to pregnenolone. A significant decrease in free GABA levels and a slight reduction in free glutamate levels have been reported in the cerbrospinal fluid of subjects with homozygous P450scc disruption, 88 suggesting that P450scc may play a role in the inhibitory/excitatory homeostasis process in the brain. Thus, it can be hypothesized that the impact of increased HSL and P450scc may involve the action of pregnenolone on CB1Rs.…”