Copper Toxicity Associated With an ATP7A-Related Complex Phenotype.

BACKGROUND: The ATP7A gene encodes a copper transporter whose mutations cause Menkes disease, occipital horn syndrome (OHS), and, less frequently, ATP7A-related distal hereditary motor neuropathy (dHMN). Here we describe a family with OHS caused by a novel mutation in the ATP7A gene, including a patient with a comorbid dHMN that worsened markedly after being treated with copper histidinate. METHODS: We studied in detail the clinical features of the patients and performed a genomic analysis by using TruSight One Expanded Sequencing Panel. Subsequently, we determined the ATP7A and ATP7B expression levels, mitochondrial membrane potential, and redox balance in cultured fibroblasts of Patient 1. RESULTS: We found a novel ATP7A late truncated mutation p.Lys1412AsnfsX15 in the two affected members of this family. The co-occurrence of OHS and dHMN in Patient 1 reveals the variable phenotypic expressivity of the variant. A severe clinical and neurophysiologic worsening was observed in the dHMN of Patient 1 when he was treated with copper replacement therapy, with a subsequent fast recovery after the copper histidinate was withdrawn. Functional studies revealed that the patient had low levels of both ATP7A and ATP7B, the other copper transporter, and high levels of superoxide ion in the mitochondria. CONCLUSIONS: Our findings broaden the clinical spectrum of ATP7A-related disorders and demonstrate that two clinical phenotypes can occur in the same patient. The copper-induced toxicity and low levels of both ATP7A and ATP7B in our patient suggest that copper accumulation in motor neurons is the pathogenic mechanism in ATP7A-related dHMN.

Perinatal atrial flutter: different therapeutic outcomes in two case reports.

Atrial flutter is a rare but potentially lethal arrhythmia, characterized by a rapid regular atrial rate, accompanied by variable degrees of atrioventricular block. Two cases of neonatal atrial flutter are described. The first case was diagnosed in utero at 38 weeks of gestation and converted to sinus rhythm by electric shock on the eighth day of life. Case two, diagnosed at 11 days old, with a background of acute bronchiolitis and tachycardia associated with a cardiac tumor, was refractory to electrical cardioversion. Both cases proved difficult to convert to sinus rhythm, but there was clinical improvement and no recurrence. These two cases exemplify the variability of outcomes achieved with anti-arrhythmic agents and direct current cardioversion.

Idiopathic congenital chylothorax treated with octreotide.

Idiopathic congenital chylothorax is defined as an abnormal accumulation of lymphatic fluid within the pleural space and is a relatively rare condition. It is a cause of progressive respiratory distress with nutritional and immunological consequences. Treatment of congenital chylothorax has been conservative management and cases unresponsive usually require surgery. We report a case of idiopathic congenital chylothorax treated with octreotide (a somatostatin analogue), avoiding surgery after failed conservative medical treatment. The patient promptly improved after initiation of endovenous octreotide treatment (10 µg/kg/h) with no observed side effects.

Congenital medium sternal cleft with partial ectopia cordis repair.

Congenital sternal malformation is a rare anomaly often diagnosed as an asymptomatic condition at birth. The authors report a clinical case of a full-term female neonate with congenital sternal cleft and partial ectopia cordis. Successful surgical repair was accomplished at 6 days of age. When surgery is performed shortly after birth, the procedure is easier and better results are achieved.