The First Case of 4H Syndrome with Type 1 Diabetes Mellitus
G��n��l B��y��ky��lmaz, B����ra Erozan ��avdarl��, Keziban Toksoy Ad��g��zel, Mehmet Ad��g��zel, ��i��dem Seher Kasapkara, Fatih G��rb��z, Mehmet Boyraz, Esra G��rka��
Author Information
G��n��l B��y��ky��lmaz: Ankara Bilkent City Hospital, Clinic of Pediatric Endocrinology, Ankara, T��rkiye ORCID
B����ra Erozan ��avdarl��: Ankara Bilkent City Hospital, Clinic of Medical Genetics, Ankara, T��rkiye ORCID
Keziban Toksoy Ad��g��zel: Ankara Bilkent City Hospital, Clinic of Pediatric Endocrinology, Ankara, T��rkiye ORCID
Mehmet Ad��g��zel: Ankara University Faculty of Medicine, Department of Radiology, Ankara, T��rkiye ORCID
��i��dem Seher Kasapkara: Ankara Y��ld��r��m Beyaz��t University Faculty of Medicine, Department of Pediatric Metabolism and Nutrition, Ankara, T��rkiye ORCID
Fatih G��rb��z: Ankara Y��ld��r��m Beyaz��t University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, T��rkiye ORCID
Mehmet Boyraz: Ankara Y��ld��r��m Beyaz��t University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, T��rkiye ORCID
Esra G��rka��: Ankara Y��ld��r��m Beyaz��t University Faculty of Medicine, Department of Pediatric Neurology, Ankara, T��rkiye ORCID
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 , and 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.
