ABSTRACT
BACKGROUND: Genetic testing is increasingly recognized as crucial in inherited nephropathies. Here, we report on an atypical presentation of a complex tubulopathy that led to an unexpected diagnosis of primary hyperoxaluria type 1 (PH1). CASE DIAGNOSIS: At 2 weeks of age, a premature boy with stunted growth was diagnosed with complex tubulopathy associating hyponatremia, hypokalemia, hypomagnesemia, hypophosphatemia, metabolic acidosis, and acute kidney injury. Despite electrolyte replacement, severe hypomagnesemia persisted while massive parallel sequencing of genes involved in hypomagnesemia yielded negative results, including HNF1ß. At 3 years of age, despite satisfactory growth, hypomagnesemia persisted and nephrocalcinosis appeared and progressed rapidly thereafter. Whole-genome analysis then revealed compound heterozygous mutations in the AGXT gene, thus leading to the diagnosis of PH1. CONCLUSION: Given the emergence of new targeted therapies, thorough genetic analysis including whole-genome analysis should be pursued, especially in case of atypical clinical presentation.
ABSTRACT
BACKGROUND: Lumasiran is the first RNA interference (RNAi) therapy of primary hyperoxaluria type 1 (PH1). Here, we report on the rapid improvement and even disappearance of nephrocalcinosis after early lumasiran therapy. CASE-DIAGNOSIS/TREATMENT: In patient 1, PH1 was suspected due to incidental discovery of nephrocalcinosis stage 3 in a 4-month-old boy. Bilateral nephrocalcinosis stage 3 was diagnosed in patient 2 at 22 months concomitantly to acute pyelonephritis. Urinary oxalate (UOx) and glycolate (UGly) were increased in both patients allowing to start lumasiran therapy before genetic confirmation. Nephrocalcinosis started to improve and disappeared after 27 months and 1 year of treatment in patients 1 and 2, respectively. CONCLUSION: These cases illustrate the efficacy of early lumasiran therapy in infants to improve and even normalize nephrocalcinosis. As proposed in the 2023 European guidelines, the interest of starting treatment quickly without waiting for genetic confirmation may have an impact on long-term outcomes.
Subject(s)
Hyperoxaluria, Primary , Nephrocalcinosis , Humans , Nephrocalcinosis/genetics , Nephrocalcinosis/diagnosis , Nephrocalcinosis/therapy , Male , Infant , Hyperoxaluria, Primary/genetics , Hyperoxaluria, Primary/diagnosis , Hyperoxaluria, Primary/therapy , Hyperoxaluria, Primary/urine , Hyperoxaluria, Primary/complications , RNAi Therapeutics/methods , Treatment Outcome , Glycolates/therapeutic use , Glycolates/urineABSTRACT
Pulmonary artery sling is a rare cause of neonatal respiratory distress. Most patients with pulmonary artery sling present in early infancy with stridor and signs of respiratory distress. Diagnosis of pulmonary artery sling, like other vascular ring anomalies, can be made using various imaging modalities, and management encompasses urgent surgical repair as a definitive treatment. This is the first paper to report a successfully managed case of an early detected left pulmonary artery sling during the first week of life in a term male patient and to evaluate the diagnostic characteristics in alliance with it. CAse REports (CARE) guidelines were followed for reporting our case. In brief, a case of full-term baby boy was born by normal vaginal delivery and shortly after birth, the baby started to have respiratory distress not improving on O2. Chest X-ray revealed right upper lobe atelectasis which persisted despite mechanical ventilation and antibiotics. A thoracic CT scan showed developmental malformation of left main pulmonary artery, confirming the diagnosis of "left pulmonary artery sling." The baby was immediately operated. One week later, chest X-ray showed gradual improvement and the baby was discharged home with no postoperative complications. Hence, we suggest that pulmonary artery sling should be suspected in any neonate with respiratory distress and unilateral lung field opacification. The fact that there are only very few reports on this disease raises a need to establish and implement well-defined guidelines and criteria for early diagnosis and management of pulmonary artery sling among newborns.