A Rare Treatable Cause of Cardiomyopathy: Primary Carnitine Deficiency.

Introduction: Primary carnitine deficiency (PCD) is a rare autosomal recessive disorder caused by loss of function mutations in the solute carrier family 22 member 5 (SLC22A5) gene that encodes a high-affinity sodium-ion-dependent organic cation transporter protein (OCTN2). Carnitine deficiency can result in acute metabolic decompensation or, in a more insidious presentation, cardiomyopathy. Cardiomyopathy associated with PCD often presents with life-threatening heart failure. This presentation also usually includes skeletal muscle myopathy. Early recognition of this disorder and treatment with carnitine can avoid life-threatening complications related to cardiomyopathy. Case Presentation: Herein, we present a 10-month-old male patient with PCD, which was diagnosed while investigating the etiology of dilated cardiomyopathy and confirmed by molecular genetic analysis. Conclusion: Homozygous c.254_265 insGGCTCGCCACC (p.I89Gfs) pathogenic variant of the SLC22A5 gene was detected. With oral L-carnitine supplementation, the free carnitine level increased up to 14 µmol/L and the symptoms disappeared. LVEF increased by 45-70%. We would like to emphasize that this problem is a combination of the metabolic decompensation and the cardiac phenotypes, which are usually separated to either phenotype.

Can therapeutic plasma exchange be life-saving in life-threatening manganese intoxication?

We present a pediatric patient presenting with life-threatening severe neurological signs, chronic liver disease, and manganese intoxication who fully recovered from neurological signs and symptoms following chelation therapy and therapeutic plasma exchange (TPE). A 13-year-old female patient was admitted with abdominal pain. Loss of consciousness and decorticate posture (GCS;M:1,V:1,M:3) developed at the 5th hour of admission. She admitted to the intensive care unit intubated. No infectious etiology that could explain acute encephalopathy was detected. Abdominal ultrasound showed granular, heterogeneous liver parenchyma suggesting chronic hepatic disease, and TPE was administered for two days since Wilson's disease and autoimmune encephalitis could not be ruled out. Cranial MRI findings were consistent with a diagnosis of manganese intoxication. On Day 3 after admission, chelation therapy and TPE were administered based on a diagnosis of manganese intoxication. Blood manganese levels at admission, day 2, and day 5 were 46, 22, and 17.5 µg/dL (NR:4.7-18.3). Control MRI results showed reduced intracranial manganese deposition, and the patient regained full consciousness. TPE as an adjunct to chelation therapy may represent an effective therapeutic option in manganese intoxication.

A rare case of primary coenzyme Q10 deficiency due to COQ9 mutation.

Background Coenzyme Q10 (CoQ10) serves as a shuttle for electrons from complexes I and II to complex III in the respiratory chain, and has important functions within the mitochondria. Primary CoQ10 deficiency is a mitochondrial disorder which has devastating effects, and which may be partially treated with exogenous CoQ10 supplementation. Case presentation A 9-month-old girl patient was referred to our clinic due to growth retardation, microcephaly and seizures. She was the third child of consanguineous parents (first-degree cousins) of Pakistani origin, born at 38 weeks gestation, weighing 2000 g after an uncomplicated pregnancy, and was hospitalized for 3 days due to respiratory distress. She had sustained clonic seizures when she was 4 months old. Physical examination showed microcephaly, truncal hypotonia and dysmorphic features. Metabolic tests were inconclusive. Abdominal ultrasonography revealed cystic appearance of the kidneys. Non-compaction of the left ventricle was detected in echocardiography. Cranial magnetic resonance imaging (MRI) showed hypoplasia of the cerebellar vermis and brain stem, corpus callosum agenesis, and cortical atrophy. A panel testing of 450 genes involved in inborn errors of metabolism (IEM) was performed that showed a novel frameshift c.384delG (Gly129Valfs*17) homozygous mutation in COQ9. A treatment of 5 mg/kg/day exogenous CoQ10 was started when she was 10 months old, and the dosage was increased to 50 mg/kg/day after the exact diagnosis. No objective neurological improvement could be observed after the adjustment of the drug dosage. Conclusions We report a case of CoQ10 deficiency due to a novel COQ9 gene mutation that adds clinical data from a newly diagnosed patient. Our case also outlines the importance of genetic panels used for specific diseases including IEM.

Mild hypotonia and recurrent seizures in an 8-month-old boy: Questions.

Hypomagnesemia with secondary hypocalcemia is a rare autosomal recessive disorder which manifests in early infancy with generalized seizures, other symptoms of neuromuscular irritability, and growth disturbances. Homozygous mutations in the magnesium transporter gene, transient receptor potential melastatin 6 (TRPM6), cause the disease. Here, we present an 8-month-old Turkish boy with a novel mutation of TRPM6. The patient, son of first-degree cousins, was hospitalized because of recurrent seizures and mild hypotonia. He had seizures since the newborn period and he had been treated with phenobarbital but there was no favorable response to therapy. His past history also revealed hypocalcemia detected on the newborn period but serum magnesium levels were not studied at that time. During hospitalization, we detected hypocalcemia, hypomagnesemia, and normal parathormone levels. Abdominal ultrasound was normal. Magnesium excretion was slightly increased. Considering the consanguinity of the parents and clinical features of the patients, genetic testing of the TRPM6 gene was performed and a novel homozygous mutation was detected as c.3178A>T. He was started on magnesium and calcium supplementation and he is symptom-free for 1 year. We would like to call attention to the measurement of serum magnesium levels in children with hypocalcemic convulsions. Early and appropriate treatment with magnesium supplementation is crucial.