Cystic fibrosis is an autosomal recessive inherited disorder that affects the lungs or the pancreas. In the case of an affected child whose parents do not have the disorder but carry one copy of the mutated gene, each sibling has a 50% chance of being a carrier of the disease. They can inherit one copy of the gene from each parent. There is a 25 % chance that the child may inherit both mutated genes and be homozygous for the trait.

The most probable diagnosis in this patient would be pulmonary stenosis. Pulmonary Stenosis:Pulmonary valve murmurs are heard in the upper left sternal edge, associated with a thrill but no desaturation in the absence of an additional shunt. The ECG changes suggest right ventricular hypertrophy. Pulmonary stenosis is often well tolerated in childhood unless severe. These should be monitored with serial echocardiography, and balloon pulmonary valvoplasty should be considered once the pressure gradient reaches 64 mmHg.Other options:- Atrial septal defect: While atrial septal defects are associated with right ventricular outflow tract murmurs, they would not cause a thrill.- Patent ductus arteriosus: PDA murmurs can be audible in the left upper sternal edge, but would normally be audible in the left infraclavicular area and be continuous rather than ejection systolic. This left to right shunt would not cause desaturation but does cause left-sided volume loading and hence left-sided ECG changes.- Tetralogy of Fallot: Ventricular septal defect, overriding aorta, subpulmonary stenosis, and right ventricular hypertrophy. This would often cause a ULSE murmur with a thrill and RVH on ECG. However, this degree of obstruction would cause shunting from right to left, and this child would be desaturated.- Ventricular septal defect: Isolated ventricular septal defects cause pansystolic murmurs at the left lower sternal edge. They would have left-sided ECG changes and normal saturations (in the absence of pulmonary hypertension).

According to the NICE guidelines, the frequency of stool passage is considered constipation when two or more of the following findings are present: Fewer than 3 stools a week, large hard stools, stools that resemble rabbit droppings| symptoms associated with defecation including distress, bleeding or straining| a history of previous episodes of a precious/current anal fissure. The child in the scenario fails to meet the criteria, and has no evidence of impacted faeces on examination. The best course of action is to encourage the parents to give the child more water to prevent dehydration, and feed the child a fibre rich diet including fruits, vegetables and high fibre bread.

Bernard- Soulier Syndrome results from a deficiency of platelet glycoprotein protein Ib, which mediates the initial interaction of platelets with the subendothelial components via the von Willebrand protein. It is a rare but severe bleeding disorder. Platelets do not aggregate to ristocetin. The platelet count is low, but, characteristically, the platelets are large, often the size of red blood cells, and may be missed on complete blood counts because most automatic counters do not count them as platelets.

Blood tests do not help in the diagnosis of jaundice except of course by telling the level of jaundice (bilirubin) and providing some corroborative evidence such as autoantibodies, tumour markers or viral titres in the case of hepatitis. Classifying causes of jaundice on the basis of ultrasound provides a quick and easy schema for diagnosing jaundice which is applicable in primary care as well as hospital based practice.

In this case scenario, the pH is too low to be fully explained by a respiratory acidosis. Usually, if there is a metabolic acidosis, the respiratory system will try to compensate by hyperventilation and reduced pCO2. In this case, however, the pCO2 is raised suggesting the presence of a respiratory component.Therefore, this boy has mixed metabolic and respiratory acidosis, most probably due to severe exacerbation of this asthma, which led to diabetic ketoacidosis.Note:Normal values:pH: 7.35 – 7.45pO2: 10 – 14 kPapCO2: 4.5 – 6 kPaBase excess (BE): -2 – 2 mmol/LHCO3: 22 – 26 mmol/L

The primary intestinal loop is formed from the midgut which gives rise to the distal half of the duodenum, the jejunum, ascending colon, proximal two thirds of the transverse colon and the ileum.

Ewing’s sarcoma is formed by small, round, blue cells, and is common in children. The usually develop in limbs, and clinical findings include pain and inflammation, with lytic destruction showing up on X-rays.

Auscultatory findings of VSD vary with the size of the defect. Small VSDs typically produce murmurs ranging from a grade 1 to 2/6 high-pitched, short systolic murmur (due to tiny defects that actually close during late systole) to a grade 3 to 4/6 holosystolic murmur (with or without thrill) at the lower left sternal border| this murmur is usually audible within the first few days of life (see table Heart Murmur Intensity). The precordium is not hyperactive, and the 2nd heart sound (S2) is normally split and has normal intensity.Moderate to large VSDs produce a holosystolic murmur that is present by age 2 to 3 wk| S2 is usually narrowly split with an accentuated pulmonary component. An apical diastolic rumble (due to increased flow through the mitral valve) and findings of heart failure (e.g., tachypnoea, dyspnoea with feeding, failure to thrive, gallop, crackles, hepatomegaly) may be present. In moderate, high-flow VSDs, the murmur is often very loud and accompanied by a thrill (grade 4 or 5 murmur). With large defects allowing equalization of left ventricular and right ventricular pressures, the systolic murmur is often attenuated.

Congenital TB symptoms typically develop during the second or third week of life and include poor feeding, poor weight gain, cough, lethargy, and irritability. Other symptoms include fever, ear discharge, and skin lesions.Signs of congenital TB include failure to thrive, icterus, hepatosplenomegaly, tachypnoea, and lymphadenopathy.

The gastrocolic reflex is a physiological reflex that involves increase in colonic motility in response to stretch in the stomach and by-products of digestion in the small intestine. It is shown to be uneven in its distribution throughout the colon, with the sigmoid colon affected more than the right side of the colon in terms of a phasic response. Various neuropeptides have been proposed as mediators of this reflex, such as serotonin, neurotensin, cholecystokinin and gastrin.

The clinical picture suggests a vitamin K deficiency haemorrhagic disease of the new-born and requires IV vitamin K and fresh frozen plasma. This usually presents with gastrointestinal bleeding, bleeding from the umbilical stump and bruising after 2–7 days.

Insertion sites and sensor sites should be rotated each time the infusion set or glucose sensor is changed. This keeps the tissue healthy and allows previous sites to completely heal before reusing them. Change infusion set every 2 to 3 days to help prevent infection.

The sensory innervation of the external auditory meatus is provided by branches of several cranial nerves. The auriculotemporal branch of the mandibular nerve (CN V3) with the nerve to external acoustic meatus supplies the anterior and superior wall of the canal with sensory innervation. The auricular branch of the vagus nerve (CN X) supplies the posterior and inferior walls of the canal, and the facial nerve (CN VII) may also supply it due to its connection with the vagus nerve.

People with Gilbert syndrome have a build-up of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia). In affected individuals, bilirubin levels fluctuate and very rarely increase to levels that cause jaundice. Gilbert syndrome is usually recognized in adolescence. If people with this condition have episodes of hyperbilirubinemia, these episodes are generally mild and typically occur when the body is under stress, for instance because of dehydration, prolonged periods without food (fasting), illness, vigorous exercise, or menstruation. Some people with Gilbert syndrome also experience abdominal discomfort or tiredness. However, approximately 30 percent of people with Gilbert syndrome have no signs or symptoms of the condition and are discovered only when routine blood tests reveal elevated unconjugated bilirubin levels.

Bilious (green) gastric aspirate or emesis indicates that the intestines are obstructed below the ampulla of Vater.Gastrointestinal (GI) endoscopy is actually considered an essential diagnostic and therapeutic technique. Upper GI endoscopy in neonatal age allows for exploration of the oesophagus, stomach and duodenum| instead lower GI endoscopy easily reaches the sigmoid-colon junction.

Protein energy malnutrition often presents in two common forms, Kwashiorkor and Marasmus. Kwashiorkor is characterised by a protein deficiency with an additional inadequate calorie intake. As a result, affected children present with oedema, muscular atrophy, and their weight for age is 60-80% of the expected weight. Their cutaneous tissue is however preserved. Marasmus on the other hand is characterised by a severe calorie deficiency leading to atrophy of the muscles and adipose tissue, with weight loss being less than 60% of the normal. In both cases, if the child is not promptly rehabilitated, the malnutrition could cause irreversible damage, such as hepatic, cardiac and renal impairments.

Observational studies fall under the category of analytic study designs and are further sub-classified as observational or experimental study designs. The goal of analytic studies is to identify and evaluate causes or risk factors of diseases or health-related events. The differentiating characteristic between observational and experimental study designs is that in the latter, the presence or absence of undergoing an intervention defines the groups. By contrast, in an observational study, the investigator does not intervene and rather simply “observes” and assesses the strength of the relationship between an exposure and disease variable.Three types of observational studies include cohort studies, case-control studies, and cross-sectional studies. Case-control and cohort studies offer specific advantages by measuring disease occurrence and its association with an exposure by offering a temporal dimension (i.e. prospective or retrospective study design). Cross-sectional studies, also known as prevalence studies, examine the data on disease and exposure at one particular time point. Because the temporal relationship between disease occurrence and exposure cannot be established, cross-sectional studies cannot assess the cause and effect relationshipDisadvantage of Cohort study is Susceptible to selection bias.

While the clinical scenario and the anosmic presentation of the child are highly suggestive of Kallmann’s syndrome, reduced testosterone, FSH and LH levels can confirm the diagnosis.Kallman’s syndrome is a recognised cause of delayed puberty secondary to hypogonadotropic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallman’s syndrome is thought to be caused by a failure of GnRH-secreting neurons to migrate to the hypothalamus.Clinical features of Kallmann’s syndrome include:- Delayed puberty- Hypogonadism, cryptorchidism- Anosmia- Low sex hormone levels – Inappropriately low/normal LH and FSH levels- Some patients can present with associated cleft lip/palate and visual/hearing defects.

Beckwith-Wiedemann Syndrome (BWS) was first characterized by Patients having abdominal wall defects, macrosomia, macroglossia, and enlarged adrenal glands. Since then, the clinical presentation has expanded to recognize hemihypertrophy/lateralized overgrowth, hyperinsulinism, omphalocele, and organomegaly as classic features of BWS.About 50% of children with BWS have hypoglycaemia and therefore patients with diagnosed BWS should be evaluated for hypoglycaemia. Hypoglycaemia in most BWS new-borns generally resolves within the first few days of life. However, in about 5% of patients that have hyperinsulinism, the severe prolonged hypoglycaemia requires escalated therapy ranging for medication (diazoxide) to partial pancreatectomy.

Neurofibromatosis is a genetic disease caused by the mutation of the neurofibromin gene on Chromosome 17. The diagnostic criteria for Neurofibromatosis type 1 are two or more of the following:-6 or more cafe au lait macules-2 or more cutaneous neurofibroma or one plexiform Neurofibroma-Axillary of groin freckling -Optic pathway glioma -2 or more Lisch nodules (hamartomas of the iris seen on slit lamp examination)-Bony dysplasia (such as sphenoid wing dysplasia, bowing of the long bones, or pseudarthrosis)-First degree relative with neurofibromatosis type 1

In a child with an age of 12 months – pincer grasp should be well developed. It is essential to have a good grasp of important milestones. Most 12-month-old children will be mobile, by standing holding onto a support, lifting one foot and moving it sideways (‘cruising’ around the furniture). They will demonstrate a neat pincer grasp, e.g. picking up a raisin or piece of paper between the tip of the index finger and the thumb. Words (or meaningful word-like utterances) are produced, but words are not usually chosen and put together deliberately by a child until after the second birthday (typically around the age of 30 months). Word combinations used earlier than this are likely to be an echo of a learnt phrase which may be understood by the child to be one single word even though they are a combination of more than one word (e.g. daddy, home). Building a tower of three cubes and following a one-step command such as ‘take off your socks’, is expected at 18 months.

Total parenteral nutrition (TPN) frequently causes derangement of liver function in children. Other options:- While line sepsis and thromboembolism are recognised complications of TPN, they do not occur frequently. – A child who is on TPN will require regular blood tests because of the potential for the development of electrolyte abnormalities. Need to observe their liver function, in order to provide TPN more accurately.

Non-Hodgkin Lymphoma: The history is of enlarged reticuloendothelial system with abnormalities in all 3 cell lines of the bone marrow (pallor, fever and petechiae). The most likely diagnosis is therefore acute (lymphoblastic) leukaemia. Lymphadenopathy may be prominent: mediastinal nodes are characteristic of T-cell leukaemia. In lymphoma the marrow involvement tends to be much less.

The development of the kidney proceeds through a series of successive phases, each marked by the development of a more advanced kidney: the pronephros, mesonephros, and metanephros. The development of the pronephric duct proceeds in a cranial-to-caudal direction. As it elongates caudally, the pronephric duct induces nearby intermediate mesoderm in the thoracolumbar area to become epithelial tubules called mesonephric tubules. Each mesonephric tubule receives a blood supply from a branch of the aorta, ending in a capillary tuft analogous to the glomerulus of the definitive nephron. The mesonephric tubule forms a capsule around the capillary tuft, allowing for filtration of blood. This filtrate flows through the mesonephric tubule and is drained into the continuation of the pronephric duct, now called the mesonephric duct or Wolffian duct. The nephrotomes of the pronephros degenerate while the mesonephric duct extends towards the most caudal end of the embryo, ultimately attaching to the cloaca.

The IM dose of adrenaline for anaphylaxis in:< 6 months: 150 micrograms (0.15ml 1 in 1,000)6 months - 6 years: 150 micrograms (0.15ml 1 in 1,000)6 - 12 years: 300 micrograms (0.3ml 1 in 1,000)Adult and child > 12 years: 500 micrograms (0.5ml 1 in 1,000)Anaphylaxis:Anaphylaxis is an acute, rapidly progressing, potentially life-threatening IgE mediated Type I hypersensitivity reaction.It involves the release of mediators from mast cells, basophils and inflammatory cells. It is characterised by oedematous swelling of the airway mucosa giving rise to dyspnoea and respiratory distress. The most common cause of anaphylaxis in children is a food allergy.Risk factors for death in patients with anaphylaxis include asthma, age 11+, peanut allergy, and delay in adrenaline administration.Management of anaphylaxis includes:- ABCD- Remove the allergen- IM adrenaline or Nebulised adrenaline- IV Hydrocortisone – pro re nata IV fluid support. – Followed by observation.

Possible complications include:- Hearing loss (which may be partial or total)- problems with memory and concentration- problems with coordination and balance- learning difficulties (which may be temporary or permanent)- epilepsy (Seizures)- cerebral palsy- speech problems- vision loss (which may be partial or total)As hearing loss is the most common complication of meningitis people recovering from the condition are usually given a hearing test to assess their hearing.

Urine culture and sensitivity is used to diagnose a urinary tract infection (UTI). A mid-stream clean catch urine sample is the most common type of sample collected. It is important to follow the clean catch process to have accurate results from an uncontaminated sample. Urine cultures can also check for infections of the bladder or kidney.

The right testicular vein is a tributary of the inferior vena cava, while the left testicular vein drains into the left renal vein.Note:The testicular venous drainage begins in the septa and these veins together with those of the tunica vasculosa converge on the posterior border of the testis as the pampiniform plexus. The pampiniform plexus, in turn, drains to the testicular vein.

People with Systemic Juvenile Idiopathic Arthritis (also known as Stills disease) can have recurrent fevers, a macular rash, joint pain, joint deformities, an enlarged liver and/or spleen, and can occasionally have polyserositis, lung involvement or pericardial effusions. Rheumatoid factor and antinuclear antibodies are usually negative. Treatment is with non-steroidal anti-inflammatory drugs (NSAIDs) and the prognosis is better than for adult rheumatoid arthritis.In pauciarticular Still’s disease, antinuclear antibodies are present. Large joints are affected and most patients develop classic features of seronegative spondylarthritis.