Abstract
BackgroundPol 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 presentationA 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.ConclusionThe 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.
Highlights
Pol III-related leukodystrophies, including 4H leukodystrophy, are recently recognized disorders that comprise hypomyelination and various neurologic and non-neurologic clinical manifestations
4H leukodystrophy is a rare disorder that includes hypomyelination, hypogonadotropic hypogonadism and dental developmental anomalies [1]. It belongs to a spectrum of clinically and radiologically overlapping diseases caused by recessive mutations in either POLR3A or POLR3B, and collectively designated as “Pol IIIrelated leukodystrophies” [1]
The patient presented hypogonadotropic hypogonadism which was accompanied by hypoprolactinemia and transient growth hormone deficiency
Summary
The report shows for the first time that an unexplained chronic bladder dysfunction should be evaluated as a possible 4H leukodystrophy, alerting to the unexpected neurologic and endocrine features in 4H leukodystrophy. It was thought to be a decline compared to the patient’s historical level of functioning: the patient had finished the compulsory education (age 7–15 years) with regular psychological assessments, was employed as a factory worker, and was able to live independently. At 32 years of age Figure 1 Magnetic resonance imaging (MRI) study in the patient with 4H leukodystrophy. (a) T1W (T1-weighted) axial scan of the brain indicating hypomyelination; (b) T2W (T2-weighted) scan of the brain and T2W-hypointensity of the globi pallidi; (c) affection of the middle cerebellar peduncles:T2W scan; (d) T2W-hypointensity of the nucleus dentatus; (e) atrophy of the cerebellum, brainstem, corpus callosum and the adenohypophisis: sagittal T1W scan; (f) the small adenohypophysis: coronal T1W scan + contrast; (g) Magnetic resonance spectroscopy: decreased choline/creatine ratio in the lesions; (h) Diffusion tensor imaging of the brain supporting hypomyelination; (i, j) the unaffected spinal cord: T2W scans. A genetic evaluation was necessitated: sequencing of the key exons and exon-intron boundaries of POLR3A using previously reported methods [6], revealed two already known diseasecausing mutations, c.272C > T (p.P91L) in exon 3 and c.3014G > A (p.R1005H) in exon 23 which segregated in the parents and proved the diagnosis of 4H leukodystrophy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
