Two separate functions of NME3 critical for cell survival underlie a neurodegenerative disorder.

We report a patient who presented with congenital hypotonia, hypoventilation, and cerebellar histopathological alterations. Exome analysis revealed a homozygous mutation in the initiation codon of the NME3 gene, which encodes an NDP kinase. The initiation-codon mutation leads to deficiency in NME3 protein expression. NME3 is a mitochondrial outer-membrane protein capable of interacting with MFN1/2, and its depletion causes dysfunction in mitochondrial dynamics. Consistently, the patient's fibroblasts were characterized by a slow rate of mitochondrial dynamics, which was reversed by expression of wild-type or catalytic-dead NME3. Moreover, glucose starvation caused mitochondrial fragmentation and cell death in the patient's cells. The expression of wild-type and catalytic-dead but not oligomerization-attenuated NME3 restored mitochondrial elongation. However, only wild-type NME3 sustained ATP production and viability. Thus, the separate functions of NME3 in mitochondrial fusion and NDP kinase cooperate in metabolic adaptation for cell survival in response to glucose starvation. Given the critical role of mitochondrial dynamics and energy requirements in neuronal development, the homozygous mutation in NME3 is linked to a fatal mitochondrial neurodegenerative disorder.

Classic Case Report of Donohue Syndrome (Leprechaunism; OMIM *246200): The Impact of Consanguineous Mating.

Donohue syndrome ([DS]; leprechaunism) describes a genetic autosomal recessive disorder that results from the presence of homozygous or compound heterozygous mutations in the insulin receptor gene (INSR; 19p13.3-p13.2).Donohue syndrome is associated with a fatal congenital form of dwarfism with features of intrauterine and postnatal growth retardation, exaggerated hyperglycemia with hyperinsulinism and dysmorphic abnormalities.We present a case of DS owing to the rarity of this syndrome (1 case in every million births). We discuss how the disease presents, its genetic underpinning, and its prevention.The case was encountered in an Arab male born on 1 September, 2014, for consanguineous parents. The delivery was via cesarean section at 37 weeks gestation due to severe intrauterine growth restriction and nonprogress labor term. The patient was admitted to the Neonatal Intensive Care Unit due to infection, and jaundice. Dysmorphic features, abnormalities of the craniofacial region, low birth weight, skin abnormalities, abdominal distension and hypertrichosis were observed. Laboratory examinations showed, hyperinsulinism, increased C-peptide, thrombocytopenia, leucopenia, and anemia.The diagnosis of DS was done based on the combinations of typical dysmorphic characteristics, clinical evaluation, supported by genetic analysis and exaggerated biochemical results. Genetic diagnosis of DS was performed through analysis of DNA via polymerase chain reaction (PCR). A qualitative real-time PCR was used, to monitor the amplification of a targeted DNA molecule during the PCR. Other technique using sequencing of the INSR gene, which permits genetic diagnosis, counseling, and antenatal diagnoses in subsequent pregnancies, were also performed.Treatment of DS is supportive and requires the combined efforts of a multidisciplinary team, which include pediatricians, endocrinologists, dermatologists, and other health care professionals. Currently, treatment with recombinant insulin-like growth factor 1 demonstrates effectiveness, and a combination treatment with insulin-like growth factor binding protein 3 resulted in an increased lifespan.There is a scarcity of genetic information on DS among the Arab population. Consanguinity is one of underlying reasons for the appearance of rare genetic disorders. Inbreeding has long been considered a controversial phenomenon. Genetic counseling and overwhelming the alertness of the negative consequences of consanguinity on public health are warranted.

First Case Report of Smith-Magenis Syndrome (SMS) Among the Arab Community in Nazareth: View and Overview.

Smith-Magenis syndrome (SMS0) is a complex and rare genetic multisystem disorder characterized by a variable pattern of cognitive deficits accompanied by a1 distinctive behavioral phenotype. SMS is characterized by subtle facial dysmorphology, short stature, sleep disturbances, and neurobehavioral abnormalities. Little is known about the manifestation of his unique case among Arab population and its strategic treatment.This study comes to present a case of SMS in an Arab newborn male who was born in spontaneous delivery on June 29, 2015, with tachypnea, tracheomalacia, and mild hypotonia. The newborn was admitted on the Neonatal Intensive Care Unit (NICU), and various laboratory examinations and clinical examinations were performed.Throughout his hospitalization, feeding difficulties appeared and thus a peripheral venous catheter was inserted in the left leg.After 22 days of follow-up and hospitalizations, the patient status improved and he was discharged with recommendations to be in follow up in pediatric outpatient clinic.However, notwithstanding the different investigations, intermittent tachypnea continued at a rate of 72 to 77 breaths/min. Search for diagnosis begin intensively owing to persistence of tachypnia, mild hypotonia, feeding difficulties, sleep disturbances, and mild dysmorphic facial features. Suspicions of genetic abnormalities were considered and blood samples were sent for chromosome analysis and for fluorescent in situ hybridization (FISH) testing.The genetic results revealed the following: cytogenetic findings: 46, XY, del(17)(p11.2) and the FISH results: del(17)(p11.2p11.2) (D17S29). The chromosome diagnosis revealed an interstitial deletion of 17p11.2 and the diagnosis of the SMS was confirmed.Accurate clinical diagnosis, therapeutic assessments and a holistic management plans, including multidiscipline therapeutic strategies, periodic neuro-developmental assessments, and an early intervention programs, are recommended.However, cytogenetic analysis or FISH using an RAI1-specific probe is the most frequently used technique for DS. Sleep and behavioral disturbances treatment include a combination of the daytime dose of acebutolol with an evening oral dose of melatonin. Melatonin as chronobiotic, antioxidant, and analgesic agent showed to be effective in different primary sleep disorders and in those associated with neurobehavioral disorders. Based on the beneficial effect of melatonin, it will be useful to use serum levels of melatonin as a follow-up test.

Severe recurrent pancreatitis in a child with ADHD after starting treatment with methylphenidate (Ritalin).

We present a case of a 10-year-old boy, who had severe relapsing pancreatitis, three times in two months within 3 weeks after starting treatment with methylphenidate (Ritalin) due to attention deficit hyperactivity disorder (ADHD). Pancreatitis due to the use of (methylphenidate) Ritalin was never published before. Attention must be made by the physicians regarding this possible complication, and this complication should be taken into consideration in every patient with abdominal pain who was newly treated with Ritalin.