Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome, with diaphragmatic defects and secondary lung hypoplasia as cardinal features. Despite it was reported first in 1979, its exact etiology has not been established to date. With this review, we would like to draw attention to the prenatal presentation of multiple congenital anomalies syndromes, resulting from defects in the synthesis of glycosylphosphatidylinositol anchors, to be considered in a prenatal assessment of fetuses with DH and Fryns-like phenotype.

Glycogen storage disease type 1b (GSD 1b) is an inherited metabolic defect caused by biallelic mutations in the SLC37A4 gene encoding microsomal glucose‐6‐phosphate (G6P) transporter in the endoplasmic reticulum (ER) membrane. Ineffective G6P transport into the ER leads to hypoglycaemia, hyperlactatemia, hyperuricemia, hypertriglyceridemia, hepato‐ and/or nephromegaly. Clinical manifestations of the disease include recurrent, severe infections and inflammatory bowel (Crohn‐like) caused by neutropenia and diminished bactericidal and fungicidal activity of neutrophils. Granulocyte colony‐stimulating factor (G‐CSF) administration is currently a standard therapy to prevent adverse effects of neutropenia, but the treatment is associated with a high risk of severe side effects. On the other hand, short‐treatment with sodium‐glucose cotransporter type 2 inhibitor – empagliflozin (EMPA) was reported to act directly on the mechanism of neutropenia and neutrophil dysfunction in GSD 1b. We observed significant improvement in clinical and laboratory parameters after introducing EMPA to treatment, that is reduced frequency of infections, lower number of bowel movements, and improved postoperative wound healing. EMPA is effective in the treatment of neutropenia in our GSD 1b patients, which allows for dose reduction and even withdrawal of G‐CSF. We did not observe any significant side effects of EMPA treatment in our patients.

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Biallelic pathogenic variants in the neuroblastoma amplified sequence (NBAS) gene were firstly (2015) identified as a cause of fever-triggered recurrent acute liver failure (RALF). Since then, some patients with NBAS deficiency presenting with neurologic features, including a motor delay, intellectual disability, muscular hypotonia and a mild brain atrophy, have been reported. Here, we describe a case of pediatric patient diagnosed with NBAS deficiency due to a homozygous c.2809C > G, p.(Pro937Ala) variant presenting with RALF with severe hyperammonemia, acquired microcephaly and progressive brain atrophy. Not reported in the literature findings include severe hyperammonemia during ALF episode, and neurologic features in the form of acquired progressive microcephaly with brain atrophy. The latter raises the hypothesis about a primary neurologic phenotype in NBAS deficiency.

BackgroundMitochondrial diseases (MDs) are heterogeneous group of disorders caused by inborn defects in the mitochondrial respiratory chain (MRC) and malfunctions of cellular oxidative phosphorylation (OXPHOS). MDs are caused by mutations both in mitochondrial and nuclear DNA. Leigh syndrome (LS) is a neurodegenerative MD with specific clinical and neuroradiological features. There is a broad clinical spectrum of MDs, including organ-specific and multiorgan presentations with symptoms occurring at any age. High energy requiring organs are most frequently involved and cardiac involvement is common. At present there is no specific treatment for MD. Ketogenic diet (KD) has been proposed as a treatment option for patients with MD with seizures or myopathy. It is suggested that KD itself may trigger cardiological complications after long-term therapy, but according to an animal model study, KD could be considered as a therapeutic option for some mitochondrial cardiomyopathies.MethodHere we present a retrospective case report on a male infant diagnosed with LS (m.12706T > C in MTND5) with severe progressive hypertrophic cardiomyopathy, with significant cardiological improvement after KD implementation .ResultsThe ketogenic diet was introduced in a male infant with clinical, biochemical and radiological features of Leigh syndrome, confirmed by next-generation sequencing (NGS) (known pathogenic variant in mtDNA), suffering from severe progressive hypertrophic cardiomyopathy and heart failure with no significant improvement on cardiological treatment, mitochondrial cocktail therapy and mechanical ventilation. The follow-up after KD initiation have shown significant clinical improvement in cardiovascular efficiency and echocardiographic parameters with no adverse effect observed so far.ConclusionScreening for cardiomyopathy is a standard of care (SoC) in the management of patients with mitochondrial disease. Although there are reports suggesting the efficacy and safety of KD in patients with mitochondrial disease, more studies are needed to understand the pathophysiology of mitochondrial diseases and to determine which patients are likely to benefit from this therapy.