J Clin Res Pediatr Endocrinol. Ahead of Print: JCRPE-22932 | DOI: 10.4274/jcrpe.galenos.2023.2023-1-15

The First Case of 4H Syndrome with Type 1 Diabetes Mellitus

Gonul Buyukyilmaz¹, Busra Erozan Cavdarlý², Keziban Toksoy Adiguzel¹, Mehmet Adiguzel³, Cigdem Seher Kasapkara⁴, Fatih Gurbuz¹, Mehmet Boyraz¹, Esra Gurkas^5
1Department of Pediatric Endocrinology, Ankara City Hospital, Ankara, Turkey
²Department of Medical Genetics, Ankara City Hospital, Ankara, Turkey
³Department of Radiology, Ankara University School of Medicine, Ankara, Turkey
⁴Department of Pediatric Metabolism and Nutrition, Ankara Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey
⁵Department of Pediatric Neurology, Ankara Yildirim Beyazit University Faculty of Medicine, Ankara, Turkey

4H syndrome is a rare progressive hypomyelinating leukodystrophy. Hypomyelination, hypodontia, and hypogonadotropic hypogonadism are the 3 classic features of 4H syndrome. Biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K gene cause 4H leukodystrophy. Herein, we present clinical features in two siblings with 4H syndrome. The first patient (16 years) presented hypogonadotropic hypogonadism, euthyroid Hashimoto's thyroiditis and type 1 diabetes mellitus. The second patient (13.5 years) showed normal physical, biochemical and hormonal examination at presentation. It was learned that he was followed up for epilepsy between the ages of 6 months and 6 years, his epilepsy medication was discontinued at the age of 6, and he did not have seizure again. T2-weighted magnetic resonance images showed increased signal intensity secondary to hypomyelination at patients. They were subsequently found to have homozygous mutation in the POLR3A gene. 4H syndrome may present with neurological and non-neurological findings in addition to classic features of 4H syndrome. Progressive neurological deterioration may occur and endocrine dysfunction may be progressive. Although multipl endocrine abnormalities associated with this disorder have been reported to date, a case accompanied by type 1 DM has not been seen in the literature. We do not know exactly whether this is coinsidans or the expansion of the phenotype. So that reporting such cases helps to determine the appropriate genotype–phenotype correlation in patients.

Keywords: 4H leukodystrophy, POLR3A, hypogonadotropic hypogonadism, Type 1 diabetes mellitus

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