Neurogenic bladder and neuroendocrine abnormalities in Pol III-related leukodystrophy.

BACKGROUND: Pol III-related leukodystrophies, including 4H leukodystrophy, are recently recognized disorders that comprise hypomyelination and various neurologic and non-neurologic clinical manifestations. We report the unique neurologic presentation of the micturition dysfunction in Pol III-related leukodystrophy and describe the novel endocrine abnormalities in this entity. CASE PRESENTATION: A 32-year-old Caucasian female exhibited chronic urinary incontinence that commenced at the age of 7 years and remained the unexplained symptom more than two decades before the onset of progressive neurologic decline. A transient growth failure and absent sexual development with hypoprolactinemia appeared in the meanwhile. Neurologic, endocrine, neuroradiologic, and genetic evaluation performed only in the patient's thirties, confirmed the diagnosis of 4H leukodystrophy as the only cause of the micturition disturbance. CONCLUSION: The report shows for the first time that an unexplained chronic bladder dysfunction should be evaluated also as a possible 4H leukodystrophy, thus alerting to the unexpected neurologic and endocrine features in 4H leukodystrophy.

4H syndrome with late-onset growth hormone deficiency caused by POLR3A mutations.

OBJECTIVE: To report a novel clinical and genetic presentation of a patient with 4H syndrome, which is a recently described leukodystrophy syndrome characterized by ataxia, hypomyelination, hypodontia, and hypogonadotropic hypogonadism. DESIGN: Case report. SETTING: University teaching hospital. PATIENT: A 20-year-old male patient with 4H syndrome. RESULTS: The patient was found to have delayed tooth eruption and a late-onset growth hormone deficiency without overt growth failure. He was a compound heterozygote for the novel missense mutations R1005H and A1331T of POLR3A, which codes for the largest subunit of RNA polymerase III. CONCLUSION: This is the first report of this type of leukodystrophy from southeastern Europe, which suggests that POLR3A mutations should be suspected in patients with hypomyelination and various central nervous system­based endocrine abnormalities.