Novel ATP6V0A4 mutation described in a Tunisian patient with distal renal tubular acidosis.

UNLABELLED: Few data regarding molecular diagnosis of primary distal renal tubular acidosis (DRTA) in Tunisian population are available. CASE REPORT: 25-day-old male patient from consanguineous parents of Tunisian origin diagnosed with DRTA and without hearing impairment observed later in life. ATP6V0A4 gene sequencing demonstrated a novel homozygous G deletion in exon 13 (c.1221delG, p.Met408CysfsX10), leading to a premature stop codon. CONCLUSION: A novel ATP6V0A4 gene mutation confirmed autosomal recessive DRTA with normal hearing in the patient. Molecular analysis may help to rapidly diagnose autosomal recessive DRTA in Tunisian population.

[An unusual etiology of acute pancreatitis]. / Une étiologie inhabituelle de pancréatite aiguë.

A 54-year-old woman consulted the emergency department for abdominal pain, vomiting and fever for 5 days. A biochemical assessment was performed and showed a lipasemia higher than 5 times normal range (264 UI/L). Hyperlipasemia is in favor of acute pancreatitis. On obtaining further history, the patient reported the SARS-CoV-2 infection two weeks ago with a laboratory investigations done the same day as the positive PCR showed a normal lipasemia. The imaging findings were suggestive of early acute pancreatitis. Acute pancreatitis secondary to SARS-CoV-2 infection is suspected.

Response to growth hormone therapy in ring chromosome 15: Review and evidence from a new case on possible beneficial effect in neurodevelopment.

Type 1 Insulin-like Growth Factor Receptor(IGF1R) plays a fundamental role in normal growth and development. Its disruption is usually characterized by severe intrauterine and postnatal growth retardation, microcephaly and neurodevelopmental delay.The efficacy of recombinant human growth hormone treatment remains a challenge for children with IGF1 resistance and pathogenic mutations of IGF1R, with limited data in patients carrying the most severe form of IGF1R defect, the ring chromosome 15. SUBJECT AND METHOD: We tested a high dose of rhGH in a new patient with ring chromosome 15, as confirmed by karyotype and CGH array. We performed a systematic review, and all published r(15) syndrome cases treated by growth hormone(GH) up to April 2023 were searched, and their response to GH therapy was recorded and summarized. RESULTS: Twelve patients with ring chromosome 15 received GH therapy according to a literature review. We expand the spectrum by the 13th case treated by GH, and we report an impressive improvement in intellectual performance and progressive catch-up growth after 5 and 20 months of follow-up. By introducing our new case in the analysis, the sex ratio was 3:10, and GH therapy was started at the age of 5.5 (3/9.4) (years) for an age of diagnosis of 4.75 (1.3/9.5) (years). The height before GH therapy was -5.1(-5.9/-4.1) SDS. The median duration of treatment was 1.7(0.9/2) (years), with a median height gain of 1(0.3/1.8) SDS and an improvement in growth velocity of 4.1(2.8/5.3) (cm/year). CONCLUSION: GH seems to be effective for r(15) syndrome patients with short stature.

Elevated serum levels of AGEs, sRAGE, and pentosidine in Tunisian patients with severity of diabetic retinopathy.

OBJECTIVES: The advanced glycation end products (AGEs)-receptor for AGE (RAGE) axis activity are implicated in diabetic vascular complications. We measured serum AGE, sRAGE and pentosidine levels in Tunisian patients with diabetic retinopathy (DR) and examined whether these biomarkers are related to the severity of DR. DESIGN AND METHODS: We included 30 healthy control subjects and 100 diabetic patients were divided into 2 subgroups: 40 patients with nonproliferative diabetic retinopathy (NPDR), and 60 patients with proliferative diabetic retinopathy (PRD). AGEs, sRAGE and pentosidine were measured in serum by ELISA. RESULTS: Serum levels of AGEs, sRAGE and pentosidine were significantly increased in patients with diabetes mellitus compared to nondiabetic controls (P<.01, P<.001, P<.001 respectively). In diabetic patients, serum AGEs, sRAGE and pentosidine levels were significantly higher in patients who had PDR than in those with NPDR (P=.001, P=.01, P=.005 respectively). Furthermore, in stepwise multivariate regression analysis, the levels of pentosidine and duration of diabetes were independently associated with severity of DR. CONCLUSION: Serum AGEs, sRAGE, and pentosidine levels are related with the presence of DR. Duration of diabetes and pentosidine were independently correlated with the severity of DR.

Does urinary stone composition and morphology help for prediction of primary hyperparathyroidism?

BACKGROUND: Primary hyperparathyroidism (HPT) is a common cause of urolithiasis. Only a few data are available on stone composition and morphology in HPT patients. METHODS: We compared the composition and morphology of stones from 264 HPT patients (143 males and 121 females) and 24 567 non-HPT stone formers (16 918 males and 7649 females) including a subgroup of 1356 patients with idiopathic hypercalciuria (IH) (1049 males and 307 females). We excluded uric acid and infection stones containing struvite. RESULTS: Calcium oxalate (CaOx) was the most prevalent crystalline species among the main components of stones in all groups. However, CaOx stones were significantly less frequent in patients with vs without HPT (51.9% vs 82.2%; P<0.0001). An inversion of CaOx crystalline phases was observed in HPT and IH patients: whewellite was predominant in 16.3% and 30.2% of cases, respectively, vs 57.4% in the non-HPT group (P<0.001), whereas weddellite was predominant in 35.6% of HPT and 49.5% of IH vs 24.8% of non-HPT stones (P<0.0001). Among calcium phosphates, brushite was 7-fold more frequent in HPT than in non-HPT patients (14.0% vs 2.2%; P<0.0001) and almost three times as frequent as in IH patients (4.9%, P<0.0001). Carbapatite was significantly more frequent in male patients with HPT vs non-HPT or IH patients (23.1% vs 8.3% and 9.9%, P<0.0001). Morphological data showed that pure type I calculi were markedly less frequent in HPT patients (1.1% vs 25.3% in non-HPT group, P<0.0001, and 9.1% in IH subgroup, P<0.001). A high occurrence of IVd calculi and of the association of types IVa and II was observed in HPT vs non-HPT and IH patients (14.4%, 2.3% and 6.3%, P<0.0001 and 58.3%, 17.2% and 29.9%, P<0.0001, respectively). CONCLUSIONS: Our data highlight a striking increase in the proportion of calcium-dependent crystalline species, especially brushite in HPT patients, with particular morphological associations in both genders which were more marked than in IH patients.

[Inherited tubular renal acidosis]. / Acidose tubulaire rénale héréditaire.

Renal tubular acidosis (RTA) is a tubulopathy characterized by metabolic acidosis with normal anion gap secondary to abnormalities of renal acidification. RTA can be classified into four main subtypes: distal RTA, proximal RTA, combined proximal and distal RTA, and hyperkalemic RTA. Distal RTA (type 1) is caused by the defect of H(+) secretion in the distal tubules and is characterized by the inability to acidify the urine below pH 5.5 during systemic acidemia. Proximal RTA (type 2) is caused by an impairment of bicarbonate reabsorption in the proximal tubules and characterized by a decreased renal bicarbonate threshold. Combined proximal and distal RTA (type 3) secondary to a reduction in tubular reclamation of bicarbonate and an inability to acidify the urine in the face of severe acidemia. Hyperkalemic RTA (type 4) may occur as a result of aldosterone deficiency or tubular insensitivity to aldosterone. Clinicians should be alert to the presence of RTA in patients with an unexplained normal anion gap acidosis, hypokalemia, recurrent nephrolithiasis and nephrocalcinosis. The mainstay of treatment of RTA remains alkali replacement.

Composition and morphology of phosphate stones and their relation with etiology.

Calcium phosphate (CaP) stones account for about 15% of all urinary stones, with a marked female preponderance, and reflect a wide diversity of etiology. Variation of the relative prevalence of CaP urolithiasis over time is disputed, and relevance of CaP stone analysis for etiologic diagnosis is underestimated or even negated. Based on the analysis of more than 50,000 stones over the past three decades, we evaluated the changes in the relative proportion of CaP stones between 1980-1989 (period 1) and 2000-2009 (period 2). In addition, using morphologic examination combined with Fourier-transform infrared analysis, we assessed the associations between CaP stone analysis and etiopathogenic factors. Between periods 1 and 2, the overall proportion of struvite-free stones remained essentially unchanged (11.6 vs. 11.1%), with a decreasing proportion of carbapatite stones (10.6 vs. 8.4%, p < 0.001) and a rising proportion of brushite stones (0.8 vs. 2.2%, p < 0.001). Hypercalciuria was associated with 87% of brushite, and 60% of carbapatite stones. Urinary tract infection was associated with presence of minor amounts of struvite and/or with a carbonation rate of carbapatite > 15%. In CaP stones associated with primary hyperparathyroidism, the main component was carbapatite in 66.9% and brushite in 29.1% of cases. Distal renal tubular acidosis was always associated with carbapatite stones exhibiting a peculiar, virtually pathognomonic, morphology. In conclusion, comprehensive analysis of stones involving morphologic examination is of clinical relevance for improved etiologic evaluation of patients with CaP urolithiasis.

Lipid and oxidative profile in hemodialysis patients: Clinical follow-up for three years.

BACKGROUND: The major cause of death for hemodialysis (HD) patients was cardiovascular morbidity; it was closely related to oxidative stress (OS). AIM: Firstly, to evaluate lipid peroxidation biomarkers on HD patients through measuring malondialdehyde (MDA) and conjugated dienes (CD), and secondly, to follow these parameters after three years undergoing HD. METHODS: One hundred patients with end stage renal diseases receiving regular hemodialysis and 100 healthy volunteers were included in this study. Routine chemical data, lipid profile and levels of MDA and CD were measured. RESULTS: The plasmatic and erythrocyte MDA levels were significantly increased in the HD patients compared to healthy subjects (p <0.001). However, an increased level on erythrocyte CD was only observed between the two study groups (p<0.001). After 3 years, a significant increased level of lipid peroxidation biomarkers was observed. CONCLUSION: The disturbance in lipid peroxidation state in HD patients was observed. At three years follow-up, oxidative stress is more pronounced with a significant increase in MDA and CD.

Methylglyoxal: A Relevant Marker of Disease Activity in Patients with Rheumatoid Arthritis.

BACKGROUND: The contribution of methylglyoxal (MGO) and soluble receptor for advanced glycation end products (sRAGE) in the presence of rheumatoid arthritis (RA) is still unknown. We investigated whether serum MGO and sRAGE were related to the presence of disease activity in RA. METHODS: 80 patients with RA and 30 control subjects were included in a cross-sectional study. The severity of RA was assessed using the disease activity score for 28 joints (DAS28). Serum MGO and sRAGE were measured by ELISA. RESULTS: Serum MGO levels were significantly higher in patients with RA versus control subjects (P < 0.001) and were increased in RA patients with higher disease activity versus RA patients with moderate disease activity (P = 0.019). Serum sRAGE concentrations were significantly decreased in RA patients with higher disease activity versus RA patients with moderate disease activity and versus control subjects (P = 0.004; P = 0.002, resp.). A multiple logistic regression analysis demonstrated that MGO was independently associated with the presence of activity disease in RA (OR = 1.17, 95% CI: 1.02-1.31, P = 0.01). CONCLUSION: Serum MGO and sRAGE levels are inversely related to the activity of RA, and MGO is independently associated with a higher disease activity of RA.

Increased serum concentrations of Nɛ-carboxymethyllysine are related to the presence and the severity of rheumatoid arthritis.

Background There are limited data regarding the contribution of advanced glycation end products in the presence of rheumatoid arthritis. We investigated whether serum Nɛ-carboxymethyllysine and pentosidine were related to the presence and the severity of rheumatoid arthritis. Methods Eighty patients with rheumatoid arthritis and 30 control subjects were included in a cross-sectional study. The severity of rheumatoid arthritis was assessed using the disease activity score for 28 joints. Serum Nɛ-carboxymethyllysine and pentosidine were measured by enzyme-linked immunosorbent assay. Results Serum Nɛ-carboxymethyllysine and pentosidine concentrations were significantly higher in patients with rheumatoid arthritis vs. control subjects ( P < 0.001). Serum Nɛ-carboxymethyllysine and pentosidine concentrations were significantly higher in rheumatoid arthritis patients with high disease activity vs. rheumatoid arthritis patients with moderate disease activity ( P < 0.001, P = 0.019, respectively). A multiple logistic regression analysis demonstrated that Nɛ-carboxymethyllysine was independently associated with the presence of rheumatoid arthritis (OR = 1.21, 95% CI: 1.05-1.39, P = 0.006). Furthermore, in a multivariate stepwise regression analysis, Nɛ-carboxymethyllysine was independently correlated with disease activity score for 28 joints (standardized ß = 0.43, P = 0.001). Conclusion Serum Nɛ-carboxymethyllysine and pentosidine were increased during rheumatoid arthritis, and Nɛ-carboxymethyllysine was independently associated with the presence and the severity of rheumatoid arthritis.

[Primary hyperoxaluria: A review]. / Hyperoxalurie primitive : une revue de la littérature.

Primary hyperoxalurias (PH) are inborn errors in the metabolism of glyoxalate and oxalate with recessive autosomal transmission. As a result, an increased endogenous production of oxalate leads to exessive urinary oxalate excretion. PH type 1, the most common form, is due to a deficiency of the peroxisomal enzyme alanine: Glyoxylate aminotransferase (AGT) in the liver. PH type 2 is due to the deficiency of the glyoxylate reductase/hydroxypyruvate réductase, present in the cytosol of hepatocytes and leucocytes. PH type 3 is linked to the gene HOGA1, encoding a mitochondrial enzyme, the 4-hydroxy-2-oxo-glutarate aldolase. Recurrent urolithiaisis and nephrocalcinosis are the markers of the disease. As a result, a progressive dysfunction of the kidneys is commonly observed. At the stage of severe chronic kidney disease, plasma oxalate increase leads to a systemic oxalosis. Diagnostic is often delayed and it based on stone analysis, cristalluria, oxaluria determination and DNA analysis. Early initiation of conservative treatment including high fluid intake and long-term co-administration of inhibitors of calcium oxalate crystallization and pyridoxine, could efficiently prevent end stage renal disease. In end stage renal failure, a combined liver-kidney transplantation corrects the enzyme defect.

Pentosidine as a biomarker for microvascular complications in type 2 diabetic patients.

Serum soluble receptor for advanced glycation end product (sRAGE) may reflect the activity of the advanced glycation end product (AGE)-receptor for advanced glycation end product (RAGE) axis, which has been proposed as a potential mechanism linking hyperglycaemia to vascular complications in diabetes. We have investigated whether serum AGEs, sRAGE and pentosidine levels were increased and correlated with microvascular complications in type 2 diabetes mellitus (DM). We included 30 healthy control subjects, and 200 diabetic patients were divided into two subgroups: 100 patients with diabetic retinopathy and 100 patients with diabetic nephropathy. AGEs, sRAGE and pentosidine were measured in serum by enzyme-linked immunosorbent assay (ELISA). Serum AGEs, sRAGE and pentosidine levels were significantly increased in diabetic patients with retinopathy and in diabetic patients with nephropathy compared to control subjects (p < 0.001). Serum AGEs, sRAGE and pentosidine levels are positively associated with microvascular complications in type 2 DM. Multiple regression analysis reveals serum pentosidine as an independent determinant of the presence of diabetic retinopathy (p = 0.004) and the presence of hypertension (p = 0.018) and hyperlipidaemia (p = 0.036). Pentosidine levels may be a biomarker for microvascular complications in type 2 diabetic patients.