A novel MAGED2 variant in a Chinese preterm newborn with transient antenatal Bartter’s syndrome with 4 years follow-up

Background Transient antenatal Bartter’s syndrome caused by MAGED2 mutation is a rare X-linked recessive renal tubular disorder. Cases reported are mostly infants, and the long-term prognosis of the disease is still under investigation. Case presentation We encountered a preterm male infant with polyhydramnios, polyuria, salt loss, hypercalciuria, nephrocalcinosis and alkalosis. Antenatal Bartter’s syndrome was suspected, but these clinical symptoms surprisingly disappeared after about 2 months. This led to the clinical diagnosis of transient antenatal Bartter’s syndrome. Gene analysis in this patient disclosed a novel variant (c.1598C > T, p.Ala533Val) in exon 12 of MAGED2 gene, and his mother was a heterozygous carrier. This patient was followed up in clinic for 4 years without recurrence of imbalance of potassium, sodium and chloride. His height and weight were in normal range, and all laboratory examinations and nephrotic ultrasound were also normal. Conclusions We reported the first Chinese case of transient antenatal Bartter’s syndrome caused by MAGED2 mutation. The 4-year follow-up of our case further demonstrates the benign prognosis of the disease and indicates that early recognition of this phenotype could avoid unnecessary treatments.

A Case Report and Literature Review of a Novel Mutation in the MAGED2 Gene of a Patient With Severe Transient Polyhydramnios

Background: Polyhydramnios occurs frequently during pregnancy. Mutations in the MAGED2 gene can cause X-linked acute early-onset polyhydramnios with a severe but transient form of antenatal Bartter's syndrome.Case Presentation: Here, we report a new novel frameshift mutation c.733_734delCT (p. Leu245GlufsTer4) in the MAGED2 gene (NM_177433.1) that caused prenatal polyhydramnios, but did not cause polyuria after birth. Follow-up was conducted for 2 months, and the baby's growth and development were normal, without polyuria and renal impairment. In addition, we identified all individuals with MAGED2 mutations reported in the literature before March 2021.Conclusion: We report a new case with a novel variant of the MAGED2 gene that caused severe hydramnios but with a good result and summary clinical characteristics in a newborn with antenatal Bartter's syndrome caused by an MAGED2 mutation. Good prenatal diagnosis and genetic consultation can improve pregnancy monitoring and newborn management.

Severe polyhydramnios as neonatal presentation of Bartter’s syndrome type IV

Introduction: Bartter’s syndrome comprises a heterogeneous group of inherited salt-losing tubulopathies. There are two forms of clinical presentation: classical and neonatal, the most severe type. Types I and II account for most of the neonatal cases. Types III and V are usually less severe. Characteristically Bartter’s syndrome type IV is a saltlosing nephropathy with mild to severe neonatal symptoms, with a specific feature - sensorineural deafness. Bartter’s syndrome type IV is the least common of all recessive types of the disease. Description: the first reported case of a Portuguese child with neurosensorial deafness, polyuria, polydipsia and failure to thrive, born prematurely due to severe polyhydramnios, with the G47R mutation in the BSND gene that causes Bartter’s syndrome type IV. Discussion: there are few published cases of BS type IV due to this mutation and those reported mostly have moderate clinical manifestations which begin later in life. The poor phenotype-genotype relationship combined with the rarity of this syndrome usually precludes an antenatal diagnosis. In the presence of a severe polyhydramnios case, with no fetal malformation detected, normal karyotype and after maternal disease exclusion, autosomal recessive diseases, including tubulopathies, should always be suspected.

A Rare Case Report of Acquired Bartters With Positive Anti Scl70 Antibody

Introduction: Bartter syndrome autosomal recessive renal tubular disorders usualy presents in infant age group or antenatallyCase Description64 years housewife, a known case of hypothyroidism with in emergency with generalized weakness and hypotension. She had an small adrenal nodule work up which showed that it was non functional. On evaluation at time of stress (blood pressure 70/50) her serum cortisol was 300nmol/l and she was therefore started on hydrocortisone. Her records revealed hypokalemia for last 2 years. Workup of hypokalemia showed kaliuresis, metabolic alkalosis, hypercalciuria and excess chloride excretion in the urine, suggestive of bartter’s syndrome. But this needed further confirmation as bartter’s is rare in this age group and also the test was done at the time of stress. She was started on spironolactone and oral potassium supplementation. CECT head done for evaluation of postural dizziness showed chronic cortical venous thrombosis. On follow up ACTH stimulated cortisol was done which showed normal cortisol level so steroid was stopped. She was readmitted one month later with hypokalemia(K-1.8 meq/l) while being on same dosage of spironolactone and potassium. Workup of hypokalemia showed same feature of bartter’s syndrome. Considering the chain of events, a suggestion of bartter’s and response to steroid, a diagnosis of acquired autoimmune bartter’s syndrome along with hypothyroidism was made. An autoimmune work up showed anti SCL 70 positive2+(++). Patient responded to steroid, spironolactone, indomethacin and oral potassium supplementation. Discussion: Bartter’s syndrome can rarely happen in old age too. Seek for autoimmune cause once we suspect acquired bartter’s. To best of our knowledge previously only one case has been reported of acquired Bartter with systemic sclerosis. Patient may develop systemic sclerosis in future as anti SCL70 antibody is very specific for it. It is positive in less than 1 % of general population. Anti SCL70 antibody is rarely positive in Sjogrens syndrome. Our patient did not feature of sjogren or systemic sclerosis even after 4 years follow up

GENETICS IN ENDOCRINOLOGY Pathophysiology, diagnosis and treatment of familial nephrogenic diabetes insipidus

For an endocrinologist, nephrogenic diabetes insipidus (NDI) is an end-organ disease, that is the antidiuretic hormone, arginine-vasopressin (AVP) is normally produced but not recognized by the kidney with an inability to concentrate urine despite elevated plasma concentrations of AVP. Polyuria with hyposthenuria and polydipsia are the cardinal clinical manifestations of the disease. For a geneticist, hereditary NDI is a rare disease with a prevalence of five per million males secondary to loss of function of the vasopressin V2 receptor, an X-linked gene, or loss of function of the water channel AQP2. These are small genes, easily sequenced, with a number of both recurrent and private mutations described as disease causing. Other inherited disorders with mild, moderate or severe inability to concentrate urine include Bartter’s syndrome and cystinosis. MAGED2 mutations are responsible for a transient form of Bartter’s syndrome with severe polyhydramnios. The purpose of this review is to describe classical phenotype findings that will help physicians to identify early, before dehydration episodes with hypernatremia, patients with familial NDI. A number of patients are still diagnosed late with repeated dehydration episodes and large dilations of the urinary tract leading to a flow obstructive nephropathy with progressive deterioration of glomerular function. Families with ancestral X-linked AVPR2 mutations could be reconstructed and all female heterozygote patients identified with subsequent perinatal genetic testing to recognize affected males within 2 weeks of birth. Prevention of dehydration episodes is of critical importance in early life and beyond and decreasing solute intake will diminish total urine output.