Titinopathy, an atypical respiratory failure

Area of Science:

• Neurology
• Genetics
• Pulmonology

Background:

• Hereditary myopathy with early respiratory failure (HME-RF) is a rare neuromuscular disorder.
• It follows an autosomal dominant inheritance pattern, presenting with muscle weakness and respiratory issues.
• Currently, no disease-modifying therapies exist for HME-RF, and its prognosis remains uncertain.

Observation:

• A 40-year-old woman presented with chronic fatigue, apathy, and recent onset of daytime sleepiness, dyspnea, and ambulation difficulties.
• Diagnostic workup revealed hypercapnic respiratory failure with severe acidemia.
• Muscle biopsy findings included cytoplasmic bodies and rimmed vacuoles, characteristic of HME-RF.

Findings:

• Genetic analysis identified a heterozygous mutation (c.95134T>C, p.Cys31712Arg) in exon 343 of the titin gene.
• This genetic finding confirmed the diagnosis of hereditary myopathy with early respiratory failure.
• The patient exhibited symptoms consistent with the established clinical presentation of the disease.

Implications:

• This case highlights the importance of genetic testing in diagnosing HME-RF.
• The identification of a titin gene mutation provides further insight into the genetic basis of this myopathy.
• Supportive care, including non-invasive ventilation, is crucial for managing respiratory complications in HME-RF patients.