BackgroundCoenzyme 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 presentationA 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.ConclusionsWe 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.

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ObjectivesCarbonic anhydrase VA (CAVA) deficiency is a rare autosomal recessive inborn error of metabolism that leads to acute metabolic crises, especially in the neonatal or infantile period. It is caused by a deficiency of the enzyme CAVA, which is encoded by the CA5A gene.Case presentationFifteen patients with homozygous pathogenic CA5A mutations involving 10 different lesions have been reported in the literature up to date. Main clinical and biochemical features of CAVA deficiency include lethargy, hyperammonemic encephalopathy, metabolic acidosis, elevated lactate and hypoglycemia. In most patients reported so far, a single metabolic decompensation attack has been reported, and they have remained stable thereafter with no further crisis.ConclusionsWe report the 16th case of CAVA deficiency, who was diagnosed by whole-exome sequencing and showed a typical course of the disease with normal development at 18 months.

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<b><i>Introduction:</i></b> Glycogen storage disease Type III (GSD III) is an autosomal recessive disease caused by the deficiency of glycogen debranching enzyme, encoded by the AGL gene. Two clinical types of the disease are most prevalent: GSD IIIa involves the liver and muscle, whereas IIIb affects only the liver. The classical dietetic management of GSD IIIa involves prevention of fasting, frequent feeds with high complex carbohydrates in small children, and a low-carb-high-protein diet in older children and adults. Recently, diets containing high amount of fat, including ketogenic and modified Atkins diet (MAD), have been suggested to have favorable outcome in GSD IIIa. <b><i>Methods:</i></b> Six patients, aged 3–31 years, with GSD IIIa received MAD for a duration of 3–7 months. Serum glucose, transaminases, creatine kinase (CK) levels, capillary ketone levels, and cardiac parameters were followed-up. <b><i>Results:</i></b> In all patients, transaminase levels dropped in response to MAD. Decrease in CK levels were detected in 5 out of 6 patients. Hypoglycemia was evident in 2 patients but was resolved by adding uncooked cornstarch to diet. <b><i>Conclusion:</i></b> Our study demonstrates that GSD IIIa may benefit from MAD both clinically and biochemically.

Background Lysinuric protein intolerance (LPI) is an autosomal recessively inherited inborn error of metabolism (IEM) caused by the defect in the dibasic cationic amino acid transporter found on the basolateral membrane of the lung, small intestine, and kidney due to mutations in the SLC7A7 gene, which encodes the y+LAT1 protein. LPI may present as an acute hyperammonemic episode or as chronic symptoms. Major clinical symptoms are feeding problems, vomiting and diarrhea, failure to thrive, hepatosplenomegaly, and cytopenia. We present a delayed diagnosis of symptomatic LPI with a homozygous mutation in the SLC7A7 gene. Case presentation A 15-year-old girl was referred to our clinic due to growth retardation and diarrhea. Physical examination showed short stature, retarded puberty, and hepatosplenomegaly. Laboratory tests showed normal complete blood count and biochemical analyses except elevated aspartate aminotransferase, triglyceride, total cholesterol, and ferritin. Peripheral blood smear and hemoglobin electrophoresis were within normal limits. Bone marrow analysis showed hemophagocytic cells. Postprandial ammonium level was found elevated. Low lysine, arginine, and ornithine and elevated glycine and alanine in plasma amino acid analysis and high amount of lysine and slightly elevated arginine and ornithine excretion in urine were detected. Molecular genetic analysis of the SLC7A7 gene showed a previously reported homozygous mutation. Low protein diet, sodium benzoate, l-carnitine, low-dose l-citrulline, and calcium replacement were initiated. The patient is now in good condition still being followed up in our department. Conclusions LPI is a metabolic disorder with multi-systemic involvement that may have severe consequences if left untreated. Initiation of early treatment is essential for the prevention of severe chronic complications. Also, confirmation of the genetic defect may provide the parents to have healthy offsprings in the future with the help of genetic counselling and preimplantation genetics.

L-2-hydroxyglutaric aciduria (L2HGA), which is a rare autosomal recessive metabolic disorder caused by mutations in the encoding L2HGDH gene. Neurological symptoms are the main predominant clinical signs. The distinctive feature is the specific multifocal lesion of the white matter detected on magnetic resonance imaging (MRI). A 7-year-old male patient of Turkish origin was admitted to the hospital because of hand tremors. Physical examination revealed macrocephaly, intention tremors, walking disability and ataxic gait. Urine organic acid analysis showed increased excretion of L-2-hydroxyglutaric acid (L2HG acid). Analysis of the L2HGDH gene revealed a novel homozygous c.368A>G, p. (Tyr123Cys) mutation. L-2-hydroxyglutaric aciduria is a cerebral organic aciduria that may lead to various neurological complications. Early recognition of symptoms of L2HGA is important for initiation of supportive therapy that may slow down the progression of the disease.