Q.18 The condition fatal infantile mitochondrial myopathy and renal dysfunction involves
I. Presence of fumarate
2. Absence of most oxidoreductases of respiratory chain
3. Presence of most oxidoreductases of respiratory chain
4. Absence of succinate
Fatal infantile mitochondrial myopathy with renal dysfunction is a rare mitochondrial disorder primarily caused by cytochrome c oxidase (complex IV) deficiency in the respiratory chain. This leads to severe hypotonia, lactic acidosis, Fanconi-like renal tubular dysfunction, and death in infancy.
Correct Answer
2. Absence of most oxidoreductases of respiratory chain
Option Analysis
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1. Presence of fumarate: Incorrect. Fumarate is a Krebs cycle intermediate; its presence is normal and unrelated to this myopathy’s pathology, which involves respiratory chain defects rather than TCA cycle accumulation.
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2. Absence of most oxidoreductases of respiratory chain: Correct. This condition features cytochrome c oxidase (complex IV) deficiency, an oxidoreductase, often with reduced activity or immunoreactive protein of other chain complexes (I, III), causing energy failure in muscle and kidney.
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3. Presence of most oxidoreductases of respiratory chain: Incorrect. While some complexes may persist, the hallmark is deficiency (absence or dysfunction) of key oxidoreductases like complex IV, not their normal presence.
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4. Absence of succinate: Incorrect. Succinate (Krebs cycle) levels may rise due to respiratory chain block, but its absence is not characteristic; pathology centers on electron transport chain oxidoreductases.
Fatal infantile mitochondrial myopathy renal dysfunction is a rare, lethal genetic disorder marked by respiratory chain oxidoreductase deficiency, especially cytochrome c oxidase (complex IV). Infants present with hypotonia, lactic acidosis, Fanconi syndrome (glycosuria, aminoaciduria, proteinuria), and die within months from respiratory failure.
Causes and Genetics
This myopathy arises from mitochondrial DNA or nuclear gene mutations impairing assembly or function of respiratory chain complexes, leading to absence of most oxidoreductases like complexes I and IV. Muscle biopsies show ragged red fibers with mitochondrial proliferation; kidney enzyme activity is reduced (e.g., 38% normal cytochrome c oxidase). Autosomal recessive inheritance predominates, with no consanguinity always noted.
Symptoms and Progression
Severe generalized weakness emerges weeks post-birth, with ptosis, poor suck, seizures, and de Toni-Fanconi-Debre renal syndrome. Lactic acidosis, elevated pyruvate, and ventilator dependence progress to death by 3-8 months. Intrafusal muscle spindle fibers uniquely retain normal enzyme activity.
Diagnosis and Management
Muscle histochemistry/immunocytochemistry reveals weak cytochrome c oxidase staining; biochemical assays confirm absent enzyme protein. No cure exists; supportive care targets acidosis and ventilation, but prognosis remains fatal. Early genetic testing aids counseling.
