NOD-m: a novel clinical score for predicting hearing loss in inherited metabolic disorders.

Objectives: Inherited metabolic disorders (IMD) are rare genetic conditions resulting from disruptions in metabolic pathways, often leading to multisystemic complications. Hearing loss (HL) is a significant but under-recognized manifestation of IMD. Its prevalence, subtypes, timing, and systemic associations remain poorly characterized. This study aims to systematically evaluate the prevalence and characteristics of HL in a large cohort of patients with IMD, emphasizing associated clinical and laboratory findings.

Methods: A retrospective review was conducted on 996 patients diagnosed with IMD between June 2012 and January 2024. Data on demographics, disease-specific features, HL subtypes, timing of diagnosis, and associated findings were analyzed. Descriptive statistics were used to summarize the findings.

Results: Hearing loss was identified in 31 patients (3.1%), with lysosomal storage disorder (LSD, 30.3%) and mitochondrial disease (MD, 25.8%) being the most frequent diagnoses. Of these patients, 19 (61.2%) were male, and the mean age at the time of IMD diagnosis was 73 ± 49 months. The most common type of HL observed was sensorineural. Most common systemic findings associated with HL (HL+) included neuromotor-cognitive delay (87.1%), organomegaly (51.6%), and dysmorphism (41.9%), alongside elevated lactate levels (38.7%) and metabolic acidosis (35.5%). The most common findings in patients with hearing loss were neuromotor-cognitive delay, organomegaly, dysmorphism, and metabolic acidosis. A composite clinical score based on these features (NOD-m) demonstrated good discriminatory performance (AUC = 0.78) for predicting hearing loss in IMD patients. The "NOD-m" code serves as a mnemonic clinical construct to aid in the early recognition of IMDs in patients with hearing loss. "NOD" reflects universal nonverbal communication, aligning with the context of auditory impairment, while "m" denotes both metabolism and metabolic acidosis-key features in the pathophysiology of these disorders.

Conclusions: Hearing loss in IMD patients is frequently associated with distinct clinical and metabolic features that can guide early recognition. The NOD-m score may serve as a practical screening aid to prompt further metabolic evaluation in patients presenting with HL.