Paediatrics: Degenerative disorders

Degenerative disorders

There are many disorders that can present with developmental regression, that is, ‘loss of skills’ and/or neurological deterioration, i.e. developing new neurological signs, or progressive intellectual deterioration. These signs always require intensive investigation.

History

·  Full developmental history: try and exclude autism.

·  Family and social history: with particular emphasis on consanguinity.

·  Medical history: check for other organ involvement—eyes, hearing, cardiac, endocrine, respiratory, viscerae.

Examination

·  All systems: storage disorders often involve other systems besides the brain, particularly face and viscera.

·  Neurological examination: this must be thorough. Look particularly for evidence of ataxia, myoclonus, dementia, dystonia, and pyramidal signs.

Investigations

History should guide a rational ap-proach to investigation, e.g. a family history of a similar disorder in a girl would make x linked disorders much less likely.

·  MRI: this form of imaging will give the largest yield. Look particularly at the white matter for leucodystrophies and see if there are any structural abnormalities (Fig. 14.6).

Other laboratory investigations: these are outlined in the Box 14.2.

Box 14.2 Investigations for developmental regression

Blood biochemistry

·U&E: renal failure

·Liver function tests: liver disease

·Plasma glucose and matching CSF glucose: glucose carrier transport (GLUT1) deficiency

·Plasma lactate and matching CSF lactate: mitochondrial cytopathy

·Ammonia: urea cycle defects

·Thyroid function tests: thyroid disease

·Urate: Lesch–Nyhan disease and purine disorders

·Plasma amino acids: aminoacidopathies

·Very long chain fatty acids: peroxisomal disorders

·Copper level: Menkes disease

·Caeruloplasmin: Wilson disease

Special blood investigations

·Vacuolated lymphocytes: Batten’s disease and other storage disorders

·WBC enzymes including Batten’s enzymes: lysosomal storage disorders and Batten’s disease

Urine

·Amino and organic acids: organic acidurias, MTHFR deficiency, sulphite oxidase deficiency

·Urate, creatinine, purine, and pyrimidine over 24hr: Lesch–Nyhan, purine/nucleotide phosphorylase deficiency

·Hydroxybutyric acid: succinate semialdehyde dehydrogenase deficiency

·Mucopolysaccharides: mucopolysaccharidoses

Tissue biopsies

·Liver: Alper’s disease

·Skin (choelesterol esterification): Niemann–Pick type C

·Muscle: mitochondrial disease

·Rectal: Batten’s disease

Eyes

Ophthalmology review: retinitis pigmentosa and other ophthalmological markers of neurological disorders e.g. cherry red spots

Electrophysiology

·Visual evoked responses: Batten’s disease

EEG: status epilepticus and regular spike wave discharges (e.g. progressive myoclonic epilepsies, such as lafora body, gangliosidoses)