4-H syndrome

Timmons et al. Peripheral and central hypomyelination with hypogonadotropic hypogonadism and hypodontia. NIH. Neurology 2006; 67:2066-2069.

Pubertal onset dysmyelinating leukodystrophy. Characteristics: young adults, absent spontaneous puberty, normal till age 7-12, borderline iq's (60s-70s), dysarthria, absent pursuit, upbeat or other nystagmus, normal sensory exam, dysmetria, long tract signs.

Sural nerve biopsies showed membraneous and other debris, loss of major and minor dense lines, increased neurofilaments. Decreased galactocerebrosidase and sphingomyelin. Immunostaining for PO protein showed clefted disruption of myelin sheaths and laminar deposits in circumferential distribution. MAG staining was similar but less definitive. Nerve conductions were normal.

MRI showed supratentorial white matter signal approximated cortex on T1, hyperintense WM on T2 (demyelination) atrophic cerebellum and thin corpus callosum.

Heterogenous Holmes-Adie syndrome has described the combination of cerebellar ataxia and hypogonadotropic hypogonadism.