The clinical presentation of mitochondrial diseases in children with progressive intellectual and neurological deterioration: a national, prospective, population-based study.

AIM: Our aim was to study the clinical presentation, mode of diagnosis, and epidemiology of mitochondrial disorders in children from the UK who have progressive intellectual and neurological deterioration (PIND).
METHOD: Since April 1997, we have identified patients aged 16 years or younger with suspected PIND through the monthly notification card sent to all UK consultant paediatricians by the British Paediatric Surveillance Unit. Clinical details obtained from reporting paediatricians are classified by an Expert Group.
RESULTS: By July 2008, 2493 cases of PIND had been reported, among which there were 112 children (69 males, 43 females) with mitochondrial diseases presenting between birth and 14 years 7 months (median 12mo), divided into 13 subgroups. In some instances, clinical features were characteristic of mitochondrial disease, but many children presented non-specifically with combinations of developmental delay, hypotonia, failure to thrive, and seizures; 16 children had multisystem disease at presentation. Mortality was high: 40 children had died. Blood and/or cerebrospinal fluid lactate measurements were abnormal in 87 children, and 47 of 78 brain magnetic resonance images showed increased basal ganglia signal. Definite diagnoses were usually made by muscle enzyme or genetic studies.
INTERPRETATION: This is a unique population-based study of the mitochondrial disorders that cause childhood neurodegenerative disease. It provides detailed information about the clinical presentation and investigation of these complex cases.