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Case Rep Endocrinol. 2015;2015:314594. doi: 10.1155/2015/314594. Epub 2015 May 31.

Endocrine Aspects of 4H Leukodystrophy: A Case Report and Review of the Literature.

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Division of Endocrinology & Metabolism, University of Calgary, 1820 Richmond Road SW, Calgary, AB, Canada T2T 5C7 ; Bone & Joint Research Group, Department of Medicine, University of Auckland, Private Bag Box 92019, Auckland 1020, New Zealand.
Departments of Pediatrics, Neurology and Neurosurgery, Division of Pediatric Neurology, Research Institute of the McGill University Health Centre, 1001 boul Décarie, Site Glen Pavilion E / Block E, Montréal, QC, Canada H4A 3J1.
Department of Medical Genetics, University of British Columbia, Child and Family Research Institute, 950 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4.
Division of Endocrinology & Metabolism, University of Calgary, 1820 Richmond Road SW, Calgary, AB, Canada T2T 5C7.



4H leukodystrophy is an autosomal recessive RNA polymerase III-related leukodystrophy, characterized by hypomyelination, with or without hypodontia (or other dental abnormalities) and hypogonadotropic hypogonadism.


We describe a 28-year-old female who presented with primary amenorrhea at the age of 19. She had a history of very mild neurological and dental abnormalities. She was found to have hypogonadotropic hypogonadism, and magnetic resonance imaging of the brain showed hypomyelination. The diagnosis of 4H leukodystrophy was made. She was subsequently found to have mutations in the POLR3B gene, which encodes the second largest subunit of RNA polymerase III. She wished to become pregnant and failed to respond to pulsatile GnRH but achieved normal follicular growth and ovulation with subcutaneous gonadotropin therapy.


Patients with 4H leukodystrophy may initially present with hypogonadotropic hypogonadism, particularly if neurological and dental manifestations are subtle. Making the diagnosis has important implications for prognosis and management. Progressive neurologic deterioration is expected, and progressive endocrine dysfunction may occur. Patients with 4H leukodystrophy should be counseled about disease progression and about this disease's autosomal recessive inheritance pattern. In those who wish to conceive, ovulation induction may be achieved with subcutaneous gonadotropin therapy, but pulsatile GnRH does not appear to be effective.

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