Mitochondrial dysfunction in a patient with Joubert syndrome.

[pyruvate dehydrogenase deficiency]

Joubert syndrome is a genetically heterogeneous disorder . The diagnostic criteria include episodic hyperventilation , abnormal eye movements , psychomotor retardation , hypotonia , ataxia , and the characteristic neuro-imaging findings (molar-tooth sign ). Many of these clinical features have been observed in new-borns with mitochondrial disorders as well . Congenital brain malformations , including cerebellar hypoplasia , have been described in pyruvate dehydrogenase deficiency . Malformations of the vermis and the cerebellar peduncles , with the lack of axonal decussations , however , are characteristic for Joubert syndrome but unique in patients with mitochondrial disorders . Here , we describe a child with Joubert syndrome presenting with primary lactic acidemia , decreased pyruvate oxidation rates , decreased ATP production , and a mildly decreased pyruvate dehydrogenase complex activity measured in a fresh muscle biopsy . Sequence analysis of the PDHc E 1 alpha gene and the PDHX genes revealed no mutations . The patient received continuous feeding through a feeding tube for two years and showed a significant clinical improvement with a complete resolution of the chronic lactic acidemia . A second muscle biopsy revealed significantly decreased pyruvate oxidation rates and ATP production , but a normal pyruvate dehydrogenase complex activity . We suggest that the described mitochondrial dysfunction in our patient is secondary to an underlying mutation leading to Joubert syndrome .

Diseases
Validation

Diseases presenting "hyperventilation" symptom

congenital diaphragmatic hernia

pyruvate dehydrogenase deficiency

This symptom has already been validated