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Case Reports
. 2025 Mar 19;17(1):103-108.
doi: 10.4274/jcrpe.galenos.2023.2023-1-15. Epub 2023 Mar 28.

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

Gönül Büyükyılmaz  1 , Büşra Erozan Çavdarlı  2 , Keziban Toksoy Adıgüzel  1 , Mehmet Adıgüzel  3 , Çiğdem Seher Kasapkara  4 , Fatih Gürbüz  5 , Mehmet Boyraz  5 , Esra Gürkaş  6
Affiliations
Case Reports

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

Gönül Büyükyılmaz et al. J Clin Res Pediatr Endocrinol. .

Abstract

4H syndrome is a rare, progressive, hypomyelinating leukodystrophy. Hypomyelination, hypodontia, and hypogonadotropic hypogonadism are the three 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 with hypogonadotropic hypogonadism, euthyroid Hashimoto’s thyroiditis and type 1 diabetes mellitus (DM). The second patient (13.5 years) showed normal physical, biochemical and hormonal examination at presentation. The second patient was followed up for epilepsy between the ages of 6 months and 6 years, when his epilepsy medication was discontinued, and he did not have seizure again. T2-weighted magnetic resonance images showed increased signal intensity secondary to hypomyelination in both. They were subsequently found to have a homozygous variant 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 multiple endocrine abnormalities associated with this disorder have been reported to date, a case accompanied by type 1 DM has not previously been published. We do not know if this was a coincidence or an expansion of the phenotype. However, 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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Conflict of interest statement

Conflict of interest: None declared.

Figures

Figure 1
Figure 1
On axial T2-weighted MRI images, hyperintense areas (black arrows) secondary to hypomyelination are seen in bilateral centrum semiovale (a) and periventricular white matter (b) MRI: magnetic resonance imaging
Figure 2
Figure 2
Schematic presentation of the genomic locus of the POLR3A gene on chromosome 10, and the results of segregation analysis of POLR3A gene c.2005C>G variant on the pedigree of the family
Figure 3
Figure 3
Axial T2-weighted MRI shows (white arrows) increased signal intensity secondary to hypomyelination in bilateral periventricular white matter MRI: magnetic resonance imaging
See this image and copyright information in PMC

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