DeCure for Leukoencephalopathy, progressive, with ovarian failure

Twenty-two women receiving cyclophosphamide for glomerulonephritis or rheumatoid arthritis were studied in 1973. Seventeen had definite or probable ovarian failure after the drug. Ovarian biopsy showed normal follicular maturation in none, and ova were seen in only two. One patient judged to have ovarian failure regained normal function ten months after stopping cyclophosphamide.

In a 2005 study of twenty-two women who had ovarian tissue cryopreserved before chemotherapy for breast cancer, Hodgkin's disease, non-Hodgkin's lymphoma, leukaemia, or brain tumour, nine (41%) had sonographic and hormonal signs of ovarian failure with ovarian volumes below 1.3 cm³, no antral follicles, and median FSH of 57.1 IU/l. Thirteen women (59%) still menstruated, and ten had seemingly normal ovarian function with median ovarian volume 6.8 cm³, median six antral follicles, FSH below 15 IU/l, and normal estradiol. All three patients who received autotransplanted ovarian tissue regained ovarian function, and two embryos were created from cryopreserved tissue after IVF. Treatment with bone-marrow transplantation or high doses of alkylating agents led to ovarian failure in all patients.

Four women aged 15 to 29 from three unrelated families were described in 1997 with a combination of central nervous system white matter disease and primary ovarian failure. All had normal initial development, but three had borderline low IQ and academic difficulties in primary school. Puberty did not develop in two patients and was arrested in a third; the fourth had premature ovarian failure at age 13. Head MRI showed diffuse white matter disease with frontal cortical atrophy in the most clinically advanced patient. All had normal karyotype and normal findings on extensive evaluations for known leukodystrophies and other metabolic diseases. Proton magnetic resonance spectroscopic imaging showed reduction of choline-containing compounds in affected white matter in all patients and reduction of N-acetylaspartate in unaffected frontal white matter of two patients. Pathological analysis showed streak ovaries in one patient and signs of hypomyelination and gliosis on brain biopsy in another.

A 2016 report describes a woman with epilepsy and neuroimaging changes consistent with leukoencephalopathy who presented with non-convulsive status epilepticus after starting hormone replacement therapy for premature ovarian failure. Genetic testing confirmed compound heterozygosity for EIF2B5 mutations, which encode a subunit of eukaryotic translation initiation factor 2B. Mutations in EIF2B1-5 result in vanishing white matter disease. The authors note that ovarian failure is a diagnostic pointer to eIF2B-related ovarioleukodystrophy. What remains missing is any prospective trial of a drug for this condition, any systematic patient stratification by genotype, and dedicated funding for a condition diagnosed in only a handful of families worldwide.