Modern Pediatrics. Ukraine. (2022). 8(128): 68-79. doi 10.15574/SP.2022.128.68
Dorosh O. I.^1,2, Bodak Kh. I.¹, Kozak Ya. R.¹, Dubey L. Ya.², Dworniak O. W.¹, Tsymbalyuk-Voloshyn I. P.¹, Dushar M. I.^2,3
1CNE of LRC «Western Ukrainian Specialized Pediatric Medical Centre», Ukraine
²Danylo Halytsky Lviv National Medical University, Ukraine
³SI «Institute of Hereditary Pathology of the NAMS of Ukraine», Lviv

For citation: Dorosh OI, Bodak KhI, Kozak YaR, Dubey LYa, Dworniak OW, Tsymbalyuk-Voloshyn IP, Dushar MI. (2022). Neurodegenerative disease with accumulation of iron in the brain in a child with hemophilia A complicated by inhibitory antibodies. Modern Pediatrics. Ukraine. 8(128): 68-79. doi 10.15574/SP.2022.128.68.
Article received: Sep 28, 2022. Accepted for publication: Dec 20, 2022.

Hemophilia A is an X-linked recessive disorder caused by a deficiency of plasma coagulation FVIII, which may be inherited or arise from a spontaneous mutation. FVIII deficiency leads to a decrease in normal hemostasis and is manifested by spontaneous or induced bleeding. As a result of hemorrhages in the central nervous system, neurological complications are possible. In such cases, doctors should be on the alert so as not to miss another accompanying pathology.
Neurodegenerative disease with iron accumulation in the brain is a genetically and clinically heterogeneous group of hereditary progressive disorders of the central nervous system with pronounced iron accumulation in the basal ganglia, which have a specific picture on magnetic resonance imaging of the brain in combination with characteristic clinical signs.
Purpose – is to describe a clinical case of a combination of two complex hereditary diseases in a 10-year-old boy, hemophilia A of moderate severity, complicated by an inhibitor, and a progressive neurodegenerative disease with accumulation of iron in the brain, with associated neurodegeneration associated with the protein of the mitochondrial membrane.
The publication reports for the first time a clinical case of a combination of two complex hereditary diseases in a 10-year-old boy, confirmed by molecular genetic studies: hemophilia A of moderate severity, complicated by an inhibitor with the detection of a large deletion of exons 23-26 in the gene, and progressive neurodegeneration with brain iron accumulation, with the presence of a pathogenic mutation of the C19orf12 gene, variant c.204_214del (p.Gly69Argfs*10) in a homozygous state, autosomal recessive type of inheritance, Mitochondrial-membrane Protein-Associated Neurodegeneration. Coagulopathy is controlled by prophylactic administration of emicizumab subcutaneously. Neurodegeneration with brain iron accumulation in the child was manifested by: Friedreich's foot, equinus feet, positive Babinski symptom, high tendon reflexes, optic nerve atrophy; partial dysplasia of both eyes; with myopia of both eyes, impaired accommodation, progressively increasing paresthesias in both legs, impaired gait, ataxic gait, coordination difficulties, muscle atrophy of both legs, visual impairment, rapid fatigue with preserved intelligence and mental development. Magnetic resonance imaging of the brain showed a moderate bilateral symmetrical lesion of the globus pallidus.
Our report confirms that the use of molecular genetic studies plays an important decisive role in the verification of the disease, often determining its type and possible complications.
The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
Keywords: hemophilia A, neurodegeneration, brain iron accumulation, C19orf12 mutation, children.
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