3-methylglutaconic aciduria with cataracts, neurologic involvement and neutropenia

CLPB (caseinolytic peptidase B) deficiency is characterized by neurologic involvement and neutropenia, which range from severe to mild. To date, a total of 26 individuals from 16 families have been reported. In severe CLPB deficiency, death usually occurs at a few months of age as a result of significant neonatal neurologic involvement (hyperekplexia or absence of voluntary movements, hypotonia or hypertonia, swallowing problems, respiratory insufficiency, and epilepsy) and severe neutropenia associated with life-threatening infections. In moderate CLPB deficiency neurologic abnormalities in infancy are comparable to but less severe than those observed in the severe phenotype (e.g., hypotonia and feeding problems) and in later childhood can include spasticity, a progressive movement disorder (ataxia, dystonia, and/or dyskinesia), epilepsy, and intellectual disability ranging from mild learning disability to limited development of all cognitive and motor functions. Neutropenia is variable, but not life threatening. In mild CLPB deficiency there is no neurologic involvement, intellect is normal, and neutropenia is mild and intermittent. Life expectancy is normal.

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