SLC29A3 mutation in a patient with syndromic diabetes with features of pigmented hypertrichotic dermatosis with insulin-dependent diabetes, H syndrome and Faisalabad histiocytosis

Compound heterozygous SLC29A3 mutation causes H syndrome in a Moroccan patient: A case report

“…It's important to note that these three patients presented the most extreme clinical features identified to date in patients with SLC29A3 mutations such as hyperpigmentation, insulin-dependent diabetes, cardiac anomalies, hearing loss, arthrogryposis and anaemia with erythroblastopenia. The idea supporting that this severe phenotype is correlated with the extreme N-terminal position of the mutation [7] cannot be controverted, since in this work the c.300+1G>C mutation was found at the heterozygous state, which may explained the fact that the affected patient presented features specific only to H syndrome. At the same position of the gene, the c.300+1G>A mutation was described in patients with Faisalabad histiocytosis [9,10], but this mutation has not been identified in the PHID or H syndromes.…”

“…The splice site mutation c.300+1G>C (p.N101LfsX34), is predicted to abolish the splice donor site of exon 2, leading to a premature termination, resulting in a truncated protein. This mutation was previously reported in a Moroccan girl [7] and in two Egyptian siblings [8] with overlapping features of pigmented hypertrichotic dermatosis with insulin-dependent diabetes, Faisalabad histiocytosis and H syndrome. It's important to note that these three patients presented the most extreme clinical features identified to date in patients with SLC29A3 mutations such as hyperpigmentation, insulin-dependent diabetes, cardiac anomalies, hearing loss, arthrogryposis and anaemia with erythroblastopenia.…”

A Case of SLC29A3 Spectrum Disorder—Unresponsive to Multiple Immunomodulatory Therapies

“…cyclophosphamide was reported to have had no effect, while ciclosporin apparently led to an improvement [13]. In Melki's case colchicine, anakinra, canakinumab and adalimumab were sequentially tested with no clinical response; non-steroidal anti-inflammatory drugs however did reduce the frequency of pyrexial episodes [10].…”

“…Inevitably, the information gleaned from such case reports must be interpreted with caution, as the patients were not all genotyped. Ciclosporin and cyclophosphamide therapy however have been tested in a patient with a confirmed SLC29A3 mutation; cyclophosphamide was reported to have had no effect, while ciclosporin apparently led to an improvement [13]. In Melki's case colchicine, anakinra, canakinumab and adalimumab were sequentially tested with no clinical response; non-steroidal anti-inflammatory drugs however did reduce the frequency of pyrexial episodes [10].…”

The expanding spectrum of rare monogenic autoinflammatory diseases

“…Due to the rarity of these disorders, a very low number of cases are reported. For example, less than five patients with clear autoinflammatory features and causative mutations have been published for each of H syndrome [10-13], Autoinflammation and PLCG2-associated antibody deficiency and Immune Dysregulation syndrome (APLAID) [14], and RANBP-Type and C3HC4-Type Zinc Finger-Containing 1 (RBCK1)-related disease [15]. These three conditions are thus cited in Tables  1 and 2 only.…”