Case History: D.S. was born premature at 29+3 weeks due to an IUGR and a path. Doppler flow, as the 3rd child of non-consanguineous parents, Apgar 6/9/10, NapH 7,01, Lactate 14,7 mmol/l. The cranial ultrasound showed post-hemorrhagic infarction on both sides on the first day of life, subsequently leading to the development of PVL. This resulted in a bilateral spastic cerebral palsy (leg>arm) within the first year of life and a severe developmental delay (at 5 years: only crawling, no speech). At 5 years of age the patient developed symptomatic epilepsy with right-sided focal seizures (start with Levetiracetam). 2 month later (may 2018) a nephrotic syndrome was diagnosed due to proteinuria, hypoalbuminemia and edema and a therapy with Prednisolon was started. Because of progressive steroid-resistent nephropathy a renal biopsy was performed, resulting in the diagnosis of focal segmental glomerulosclerosis. A therapy with cyclosporine A was initiated. Arterial hypertension (mean arterial pressure > 140 mmHg) was treated with Amlodipin and Losartan (Ramipril caused a dry cough). Due to recurring epileptic focal and generalized seizures (including a epileptic status over 55 min., cMRI showed no ischemic lesions) the anticonvulsive Medication was changed to Lamotrigin + Oxcarbazepin. In July 2018 the boy developed a sudden left-sided facial- and occulomotornerve paralysis. The MRI showed fresh ischemic infarction of the right insula region. We started to heparinize at a therapeutic dosage immediately. Shortly after we received the results of the genetic testing (performed due to the steroid-resistant nephropathy): the patient carries two compound-heterozygous pathogenic mutations in the SMARCAL1 gene. Subsequently a T-cell-deficiency was also diagnosed.

Casuistry: We report about a boy with a psychomotor developmental disorder who showed a hemi- symptomatology with head tilt to the right, loss of strength of the right leg, ataxia, dysarthria, first when he was 3,4 years old. The symptoms were reversible after 10 min. An ischaemic stroke was suspected, a cMRI was performed, which showed a normal result. At the beginning, the situations occurred every 2–5 months, more frequently in the course of time, were alternating and triggered by heat (bathing, heat in the bus), joy and physical exercise. The duration was a few minutes to several hours, a maximum of 2 days, followed by complete recovery. The best therapy was sleep. After some years the boy showed In addition to the triggered movement disorders continuous cerebellar signs (ataxia, tremor, dysarthria, lack of fast eye saccades), epileptic activity in the EEG, areflexia, bradyskinesia and a degenerative course of intellectual abilities. In the 2nd cMRIT a cerebellar atrophy was observed.

N-alpha-acetylation is one of the most common co-translational protein modifications in humans and is essential for normal cell function. NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively. Through a genotype-first approach with exome sequencing, we identified and phenotypically characterized 30 individuals from 30 unrelated families with 17 different de novo or inherited, dominantly acting missense variants in NAA10 or NAA15. Clinical features of affected individuals include variable levels of intellectual disability, delayed speech and motor milestones and autism spectrum disorder. Additionally, some subjects present with mild craniofacial dysmorphology, congenital cardiac anomalies and seizures. One of the individuals is an 11-year-old boy with a frameshift variant in exon 7 of NAA10, who presents most notably with microphthalmia, which confirms a prior finding with a single family with Lenz microphthalmia syndrome. Biochemical analyses of variants as part of the human NatA complex, as well as enzymatic analyses with and without the HYPK regulatory subunit, help to explain some of the phenotypic differences seen among the different variants.

Case History: Our patient developed first symptoms (atopic dermatitis) at the age of seven month. At 10 month a failure to thrive was diagnosed and he developed watery diarrhea. The bloodwork showed eosinophilia of 28%, high immunoglobulin E (8664 kU/l) and low immunoglobulin M < 0,25 g/l. Endoscopy showed ulcerative inflammation of the duodenum and focal Ulceration of the Colon. The histologic samples showed increased eosinophil granulocytes as well. Eosinophil enterocolitis was diagnosed and a diet with amino-acid-hydrolyzate was started, with add on therapy of Prednisolon (2 mg/kg/d) later on. At the age of 16 month the boy developed steroid-resistent-nephrotic syndrome. Renal biopsy showed membranous Glomerulonephritis and a therapy with Cyclosporin A and Ramipril was started which led to remission. At 18 month (shortly after CSA was started) the boy suffered an ischemic stroke of the right A. cerebri media (therapy with Cyclosporine A, Prednisolon and Ramipril at the time) and showed paresis of the left arm as well as central facialnerve paresis of the right side. Therapy with acetylsalicylic acid (4 mg/kg/d) and unfractionated heparin (2 mg(kg/d) was started. IPEX-Syndrome was suspected and genetic testing showed a hemizygous Missense Mutation in the FOX3 gene (c.1010G>A). Testing of the parents showed no carrier status. At the age of 21 month allogenic bone marrow transplant was performed. Immunosupressive Therapy with cyclosporine A and Prednisolon as well as the therapy with Ramipril were ended 3–5 month later.

Kinder mit chronischen Kopfschmerzen sind in ihrer Lebensqualität ähnlich beeinträchtigt wie Kindern mit einer onkologischen Erkrankung. Besonders wichtig sind für die Kinder nicht-medikamentöse Therapieoptionen, wie eine Kopfschmerzschulung durch ein multimodales kognitiv-behaviorales Training, das wir in unserer Klinik seit 2006 durchführen.

Heftiges Erbrechen, das ohne erkennbare Ursache episodisch wiederkehrt, lässt nicht nur die betroffenen Kinder leiden, sondern verursacht auch bei den Eltern große Ängste. Wird dann vom Kinderarzt die Diagnose “zyklisches Erbrechen” gestellt, bedeutet dies oft eine so erhebliche psychische Entlastung, dass gar keine weitere Therapie mehr nötig ist.