Nemaline rods and complex I deficiency in three infants with hypotonia, motor delay and failure to thrive

Area of Science:

• Biochemistry
• Genetics
• Neuromuscular Disorders

Background:

• Nemaline rods are a known morphological abnormality in muscle tissue, primarily associated with nemaline myopathy.
• Deficiencies in mitochondrial respiratory chain complex I are linked to various genetic disorders, often presenting with neurological and muscular symptoms.
• Previous research has documented diverse muscle biopsy findings in complex I deficiency but not nemaline rods.

Observation:

• Three infants presented with failure to thrive from birth.
• Hypotonia and muscle weakness were observed within the first three months of life in all affected infants.
• Muscle biopsies revealed nemaline rods, and biochemical analyses showed isolated complex I deficiency.

Findings:

• This is the first reported instance of nemaline rods co-occurring with isolated complex I deficiency.
• The combination suggests a potential link between mitochondrial dysfunction and specific muscle structural abnormalities.
• The genetic basis for this combined presentation remains to be elucidated.

Implications:

• This finding expands the spectrum of clinical and pathological manifestations of complex I deficiency.
• It may prompt re-evaluation of muscle biopsy findings in infants with unexplained hypotonia and failure to thrive.
• Further research is needed to understand the underlying molecular mechanisms connecting these two conditions.