H syndrome: A review of treatment options and a hypothesis of phenotypic variability

Nofal, Hagar; Alakad, Rania; Nofal, Ahmad; Rabie, Eman; Chaikul, T.; Chiu, Frank Po‐Chao; Pramanik, Rashida; Alabdulkareem, Ahmad; Onoufriadis, Alexandros

doi:10.1111/dth.15082

Cited by 8 publications

(8 citation statements)

References 20 publications

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“…Colchicine, anti-IL1, and Tumor necrosis factor (TNF)-alpha therapy seem to be ineffective ( 15 ). Systemic corticosteroids showed good results but with important harmful long-term effect, especially among diabetic patients diagnosed as H syndrome ( 16 ). Some of these patients partially responded to a methotrexate treatment followed by a notable improvement on hyperpigmentation, joint stiffness, and arthritis ( 17 ).…”

Section: Discussionmentioning

confidence: 99%

H syndrome treated with Tocilizumab: two case reports and literature review

et al. 2023

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H syndrome is a rare autosomal recessive genetic disorder characterized by the following clinical features: cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, short stature, hallux valgus, hyperglycemia, fixed flexion contractures of the toe joints, and the proximal interphalangeal joints. In rare cases, autoinflammatory and lymphoproliferative manifestations have also been reported. This disorder is due to loss-of-function mutations in SLC29A3 gene, which encode the equilibrative nucleoside transporter ENT3. This deficiency leads to abnormal function and proliferation of histiocytes. H syndrome is part of the R-group of histiocytosis. We report two different cases, one was diagnosed in adulthood and the other in childhood. The first case reported is a 37-year-old woman suffering from H syndrome with an autoinflammatory systemic disease that begins in adulthood (fever and diffuse organ’s infiltration) and with cutaneous, articular, auditory, and endocrinological manifestations since childhood. The second case reported is a 2-year-old girl with autoinflammatory, endocrine, and cutaneous symptoms (fever, lymphadenopathy, organomegaly, growth delay, and cutaneous hyperpigmentation). Homozygous mutations in SLC29A3 confirmed the diagnosis of H syndrome in both cases. Each patient was treated with Tocilizumab with a significant improvement for lymphoproliferative, autoinflammatory, and cutaneous manifestations. Both cases were reported to show the multiple characteristics of this rare syndrome, which can be diagnosed either in childhood or in adulthood. In addition, an overview of the literature suggested Tocilizumab efficiency.

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Section: Discussionmentioning

confidence: 99%

H syndrome treated with Tocilizumab: two case reports and literature review

et al. 2023

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“…Immunosuppressants that have been tried in treatment are systemic corticosteroids,22 methotrexate,23 Tumour necrosis factor (TNF) inhibitors,22 mycophenolate,24 thalidomide,18 interferon‐alpha, anakinra and tocilizumab 25. Despite this, the therapy regimens were ineffective or yielded partial results 2. Recent reports of promising responses to tocilizumab have been reported 25.…”

Section: Discussionmentioning

confidence: 99%

“…H-syndrome is an autosomal recessive disorder of abnormal histiocyte proliferation caused by a mutation in SLC29A3. The first case was described in 2008,1 and since then, there have been 134 cases published in the literature 2. Its varied manifestations temporally evolve over time and may mimic many rheumatological manifestations, leading to diagnostic and therapeutic delays 3.…”

Section: Introductionmentioning

confidence: 99%

Case report of H-syndrome with a review from a rheumatological perspective

Yadav

Balakrishnan

2022

BMJ Case Rep

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A woman in her 20s, symptomatic since the age of 4 with short stature, hearing loss, skin hyperpigmentation and induration over the medial aspect of the thigh, hypertrichosis, histiocytes on biopsy, lymphadenopathy, dilated scleral vessels, pancreatic exocrine deficiency, pericardial thickening, swelling of the eyelids and resistant retroperitoneal fibrosis. Whole-genome sequencing showed a mutation in SLC29A3, confirming ‘H’-syndrome. She is on steroids and methotrexate. This case highlights the rheumatological mimics of this rare disorder.

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“…On the other hand, a significant number of patients develop autoinflammatory complications, and inflammatory-related pathways are dysregulated in immune system cells from H and Rosay–Dorfman syndrome patients [ 75 ]. Although only a few case reports are available in the literature, it seems likely that targeting the inflammatory component of the disease would result in some clinical improvement [ 76 , 77 , 78 ].…”

Section: Nucleoside and Nucleobase Transporter Protein Variants And D...mentioning

confidence: 99%

Inborn Errors of Nucleoside Transporter (NT)-Encoding Genes (SLC28 and SLC29)

Pastor‐Anglada

Mata-Ventosa

Pérez-Torras

2022

IJMS

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The proper regulation of nucleotide pools is essential for all types of cellular functions and depends on de novo nucleotide biosynthesis, salvage, and degradation pathways. Despite the apparent essentiality of these processes, a significant number of rare diseases associated with mutations in genes encoding various enzymes of these pathways have been already identified, and others are likely yet to come. However, knowledge on genetic alterations impacting on nucleoside and nucleobase transporters is still limited. At this moment three gene-encoding nucleoside and nucleobase transporter proteins have been reported to be mutated in humans, SLC29A1, SLC29A3, and SLC28A1, impacting on the expression and function of ENT1, ENT3, and CNT1, respectively. ENT1 alterations determine Augustine-null blood type and cause ectopic calcification during aging. ENT3 deficiency translates into various clinical manifestations and syndromes, altogether listed in the OMIM catalog as histiocytosis-lymphoadenopathy plus syndrome (OMIM#602782). CNT1 deficiency causes uridine-cytidineuria (URCTU) (OMIM#618477), a unique type of pyrimidineuria with an as yet not well-known clinical impact. Increasing knowledge on the physiological, molecular and structural features of these transporter proteins is helping us to better understand the biological basis behind the biochemical and clinical manifestations caused by these deficiencies. Moreover, they also support the view that some metabolic compensation might occur in these disturbances, because they do not seem to significantly impact nucleotide homeostasis, but rather other biological events associated with particular subtypes of transporter proteins.

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H syndrome: A review of treatment options and a hypothesis of phenotypic variability

Cited by 8 publications

References 20 publications

H syndrome treated with Tocilizumab: two case reports and literature review

H syndrome treated with Tocilizumab: two case reports and literature review

Case report of H-syndrome with a review from a rheumatological perspective

Inborn Errors of Nucleoside Transporter (NT)-Encoding Genes (SLC28 and SLC29)

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