Autoinflammation in addition to combined immunodeficiency: SLC29A3 gene defect

Çağdaş, Deniz; Surucu, Naz; Tan, Çağman; Kayaoğlu, Başak; Özgül, Rıza Köksal; Akkaya-Ulum, Yeliz Z.; Aydınoğlu, Ayşe Tülay; Aytaç, Selin; Gümrük, Fatma; Balcı-Hayta, Burcu; Balcı-Peynircioğlu, Banu; Özen, Seza; Gürsel, Mayda; Tezcan, İlhan

doi:10.1016/j.molimm.2020.02.014

Cited by 22 publications

(14 citation statements)

References 55 publications

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“…Thus, H-syndrome may be considered as monogenic autoinflammatory19 20 syndrome with fibrosing pathology,21 which may require immunosuppressive treatment. Literature regarding the treatment of H-syndrome is scarce, with most authors reporting inconsistent and overall poor or partial response to multiple immunosuppressants 18.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

Yadav

Balakrishnan

2022

BMJ Case Rep

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“…In this way, therapeutic benefit could be suggested for anti-cytokine biologicals. However, several of these treatments have not been effective, with various studies showing poor response to anti IL-1 or TNF-alpha treatment, despite high serum levels of IL-1 and TNF [ 3 , 10 , 13 , 16 , 21 , 22 ]. Similarly, Mistry et al reported a patient with no clinical response, but with c-reactive protein normalization after Tocilizumab treatment [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia

et al. 2021

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Background H syndrome (HS) is a rare autoinflammatory disease caused by a mutation in the solute carrier family 29, member 3 (SCL29A3) gene. It has a variable clinical presentation and little phenotype-genotype correlation. The pathognomonic sign of HS is cutaneous hyperpigmentation located mainly in the inner thighs and often accompanied by other systemic manifestations. Improvement after tocilizumab treatment has been reported in a few patients with HS. We report the first patient with HS who presented cardiogenic shock, multiorgan infiltration, and digital ischemia. Case presentation 8-year-old boy born to consanguineous parents of Moroccan origin who was admitted to the intensive care unit during the Coronavirus Disease-2019 (COVID-19) pandemic with tachypnoea, tachycardia, and oliguria. Echocardiography showed dilated cardiomyopathy and severe systolic dysfunction compatible with cardiogenic shock. Additionally, he presented with multiple organ dysfunction syndrome. SARS-CoV-2 polymerase chain reaction (PCR) and antibody detection by chromatographic immunoassay were negative. A previously ordered gene panel for pre-existing sensorineural hearing loss showed a pathological mutation in the SCL29A3 gene compatible with H syndrome. Computed tomography scan revealed extensive alveolar infiltrates in the lungs and multiple poor defined hypodense lesions in liver, spleen, and kidneys; adenopathy; and cardiomegaly with left ventricle subendocardial nodules. Invasive mechanical ventilation, broad antibiotic and antifungal coverage showed no significant response. Therefore, Tocilizumab as compassionate use together with pulsed intravenous methylprednisolone was initiated. Improvement was impressive leading to normalization of inflammation markers, liver and kidney function, and stabilising heart function. Two weeks later, he was discharged and has been clinically well since then on two weekly administration of Tocilizumab. Conclusions We report the most severe disease course produced by HS described so far in the literature. Our patient’s manifestations included uncommon, new complications such as acute heart failure with severe systolic dysfunction, multi-organ cell infiltrate, and digital ischemia. Most of the clinical symptoms of our patient could have been explained by SARS-CoV-2, demonstrating the importance of a detailed differential diagnosis to ensure optimal treatment. Although the mechanism of autoinflammation of HS remains uncertain, the good response of our patient to Tocilizumab makes a case for the important role of IL-6 in this syndrome and for considering Tocilizumab as a first-line treatment, at least in severely affected patients.

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“…One of the mitochondrial cytopathy-associated features is progressive hearing loss without vestibular failure [ 2 ]. Thus, the mitochondrial defect is thought to be the reason for deafness in some H syndrome patients [ 3 ]. In our patient, no balance disorder was detected by the initial vestibular assessment we could perform.…”

Section: Discussionmentioning

confidence: 99%

Audiological findings of a patient with H syndrome: case report

Hussein

Altın

Bajin

2021

Egypt J Otolaryngol

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Background H syndrome is an autosomal recessive disorder caused by mutations in SLC29A3. Hyperpigmentation, hypertrichosis, hyperglycemia, and hearing loss are some characteristics of this disorder, and it has a prevalence of < 1/1000. The aim of this report is to spread awareness among otologists, audiologists, and pediatricians about this syndrome and its audiological features. Case presentation An 8-year-old male with a diagnosed H syndrome registered to our clinic with a complaint of hearing loss. The patient was diagnosed with hearing loss in a different clinic using only the air-conducted click auditory brainstem response test which showed wave V at 60 dB nHL for the right ear and at 80 dB nHL for the left ear. The initially performed pure tone audiometry (PTA) test in our clinic revealed a bilateral asymmetric hearing loss with a moderate sensorineural hearing loss in the right ear and a profound mixed hearing loss in the left ear. The performed air conducted click auditory brainstem response (ABR) result showed wave V at 55 dB nHL for the right ear and at 70 dB nHL for the left ear. Then, the repeated PTA test revealed a mild-severe sensorineural sloping hearing loss in the right ear and a severe sensorineural hearing loss in the left ear. Conclusion Although hearing thresholds in H syndrome could be within normal limits in some patients, sensorineural hearing loss is an important characteristic feature for this syndrome. Sensorineural hearing loss could be progressive or of sudden onset and ranges from mild to profound. Thus, it must be taken into consideration to apply the audiological follow-up regularly and paying attention to the patient’s complaints; also, a regular follow-up for language development of children with H syndrome and for the hearing aids is advised.

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Autoinflammation in addition to combined immunodeficiency: SLC29A3 gene defect

Cited by 22 publications

References 55 publications

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

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

Patient with H syndrome, cardiogenic shock, multiorgan infiltration, and digital ischemia

Audiological findings of a patient with H syndrome: case report

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