Renal failure and generalized epilepsy as leading symptoms of a respiratory chain defect (complex 1)

Case report: Two children of consanguineous Turkish parents are reported. The son was noticed to have congenital hypothyroidism after birth. At the age of 9 months he was admitted to hospital for chronic renal failure, failure to thrive and cyclic thrombocytopenia. Renal puncture at the age of 38 months showed mild atrophy of the tubuli and interstitial fibrosis.

4½ years old, the boy developed myoclonic-astatic epilepsy with absences. Under treatment with valproic acid symptomatic pancreatitis appeared. Thus treatment was changed to phenobarbital and ethosuximide. Mild mental retardation was diagnosed.

At the age of 9 years epileptic myocloni and absences recurred and anticonvulsive treatment was changed to lamotrigine, clobazam and mesuximide. Peritoneal dialysis (CCPD) had to be started due to endstage renal failure.

Acute congestive heart failure due to a dilatative hypertrophic cardiomyopathy occurred at the age of 10 4/12 years. Muscle biopsy lead to the diagnosis of complex 1 deficiency of the respiratory chain. Mutation screening of the mitochondrial DNA was normal. Blood and urine lactate continued to be in normal range whilst CSF lactate was elevated. On MRI mild hyperintensitive lesions in the cerebellar white matter were found on T2w and FLAIR images.

Treatment with carnitine, vitamin B1 and B2, Q10 and a high fat diet was started. The course was complicated by the occurrence of hypertriglyceridemia, chronic pancreatitis, gastrointestinal dysmotility and generalized seizures. The patient died at the age of 11 years in cardiac failure.

The younger sister developed chronic renal failure at 5 years and deteriorated rapidly at the age of 8 years with endstage renal failure, lactacidosis, dilatative hypertrophic cardiomyopathy and generalized spikes and waves on EEG.

Conclusion: Two siblings with an unusual manifestation of a complex I deficiency of the respiratory chain with chronic renal failure and generalized epilepsy are reported. Mild lactic acidosis and discrete myopathy was observed only in the final stage of the course.