CONTEXT: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. OBJECTIVE: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. DESIGN: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. SETTING: This was a multicenter retrospective study using information collected from 3 predominant centers. PATIENTS: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. MAIN OUTCOME MEASURES: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. RESULTS: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. CONCLUSIONS: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.

• Klíčová slova
• 4H leukodystrophy, POLR3-related leukodystrophy, hypogonadotropic hypogonadism, hypomyelination,
• MeSH
• biologická variabilita populace MeSH
• dědičné demyelinizační nemoci CNS komplikace   epidemiologie   genetika   MeSH
• dítě MeSH
• DNA řízené RNA-polymerasy genetika   MeSH
• dospělí MeSH
• genetická heterogenita MeSH
• hypogonadismus epidemiologie   etiologie   MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• mitochondriální nemoci komplikace   epidemiologie   genetika   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• nemoci endokrinního systému epidemiologie   etiologie   genetika   MeSH
• novorozenec MeSH
• poruchy růstu epidemiologie   etiologie   genetika   MeSH
• předškolní dítě MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• RNA-polymerasa III genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• DNA řízené RNA-polymerasy MeSH
• POLR1C protein, human MeSH Prohlížeč
• POLR3A protein, human MeSH Prohlížeč
• POLR3B protein, human MeSH Prohlížeč
• RNA-polymerasa III MeSH