Fetal Alcohol Syndrome

High levels of alcohol ingestion during pregnancy can be damaging to embryonic and fetal development.

Incidence:
A specific pattern of malformation identified as fetal alcohol syndrome has been documented, and major and minor components of the syndrome are expressed in 1–2 infants/1,000 live births.

Both moderate and high levels of alcohol intake during early pregnancy may result in alterations in growth and morphogenesis of the fetus; the greater the intake, the more severe the signs. Infants born to heavy drinkers have twice the risk of abnormality as those born to moderate drinkers; 32% of infants born to heavy drinkers had congenital anomalies as compared with 9% in the abstinent and 14% in the moderate group. Additional maternal risk factors associated with fetal alcohol syndrome are advanced maternal age, low socioeconomic status, poor psychologic indicators, and binge drinking.

Clinical Features:
Characteristics of fetal alcohol syndrome include

(1) prenatal onset and persistence of growth deficiency for length, weight, and head circumference;

(2) facial abnormalities, including short palpebral fissures, epicanthal folds, maxillary hypoplasia, micrognathia, smooth philtrum, and a thin, smooth upper lip ;

(3) cardiac defects, primarily septal defects;

(4) minor joint and limb abnormalities, including some restriction of movement and altered palmar crease patterns; and 

(5) delayed development and mental deficiency varying from borderline to severe.

Introduction To Abetalipoprotienemia

This rare autosomal recessive disorder of lipoprotein metabolism is associated with severe fat malabsorption from birth.

Clinical Features:
Children fail to thrive during the 1st year of life, and their stools are pale, foul smelling, and bulky. The abdomen is distended, and deep tendon reflexes are absent as a result of peripheral neuropathy, which is secondary to vitamin E deficiency. Intellectual development tends to be slow. After 10 yr of age, intestinal symptoms are less severe, ataxia develops, and there is a loss of position and vibration sensation with the onset of intention tremors. These last symptoms reflect involvement of the posterior columns, cerebellum, and basal ganglia. In adolescence, atypical retinitis pigmentosa develops.

Diagnosis:
Diagnosis rests on finding acanthocytes in the peripheral blood and extremely low plasma levels of cholesterol (<50 mg/dL); triglycerides are very low (<20 mg/dL). Chylomicrons and very low density lipoproteins are not detectable, and the low-density lipoprotein (LDL) fraction is virtually absent from the circulation; marked triglyceride accumulation in villus enterocytes occurs in the fasting duodenal mucosa. Steatorrhea occurs in younger patients, but other processes of assimilation are intact. Rickets may be an unusual initial manifestation of abetalipoproteinemia and hypobetalipoproteinemia. Rickets is caused by steatorrhea-induced calcium losses. Patients have mutations of the microsomal triglyceride transfer protein (MTP) gene, resulting in absence of MTP function in the small bowel. This protein is required for normal assembly and secretion of very low density lipoproteins and chylomicrons.

Brief Summary of Tumor Lysis Syndrome

Tumor lysis syndrome consists of hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia in a patient presenting with leukemia or lymphoma, especially those with a very high white blood cell count, Burkitt leukemia/lymphoma, or T-cell leukemia/lymphoma.

Cause:
Tumor lysis can occur prior to the onset of therapy due to spontaneous blast cell breakdown, but more typically occurs after initiating therapy. Tumor lysis syndrome has rarely been reported in children with other solid tumors. In order to prevent acute renal failure, it is essential that tumor lysis be treated aggressively.

Laboratory tests:
A patient with suspected tumor lysis syndrome should have the following laboratory studies performed at the time of presentation: CBC with manual differential, and chemistry panel (to include potassium, creatinine, calcium, phosphorus, and uric acid).

Therapy:

• Therapy for tumor lysis syndrome includes IV hydration at 2 or more times maintenance (~3,000 mL/m2/day), urinary alkalinization, and allopurinol to decrease the formation of uric acid.
• Potassium should not be included in the IV fluid.

Clinical Manifestations of Classic Phenylketonuria (PKU).

Severe hyperphenylalaninemia (plasma phenylalanine levels >20 mg/dL), if untreated, invariably results in the development of signs and symptoms of classic PKU, except in rare unpredictable occasions.

Clinical Features:
The affected infant is normal at birth. Mental retardation may develop gradually and may not be evident for the 1st few months. It is usually severe, and most patients require institutional care if the condition remains untreated. Vomiting, sometimes severe enough to be misdiagnosed as pyloric stenosis, may be an early symptom. Older untreated children become hyperactive, with purposeless movements, rhythmic rocking, and athetosis.

Physical Examination:
On physical examination, these infants are lighter in their complexion than unaffected siblings. Some may have a seborrheic or eczematoid rash, which is usually mild and disappears as the child grows older. These children have an unpleasant odor of phenylacetic acid, which has been described as musty or mousey. There are no consistent findings on neurologic examination. Most infants are hypertonic with hyperactive deep tendon reflexes. About 25% of children have seizures, and more than 50% have electroencephalographic abnormalities. Microcephaly, prominent maxilla with widely spaced teeth, enamel hypoplasia, and growth retardation are other common findings in untreated children.

Overweight and Obesity in Children

Obesity and overweight are terms that are commonly used interchangeably in children, with overweight being the preferred term. As the prevalence of overweight has increased in children and adolescents, complications of overweight are now well recognized in children.

Pathogenesis:
Overweight results from a dysregulation of caloric intake and energy expenditure. A complex interplay between each individual’s genetic predispositions and the environment affects an intricate system that controls appetite and energy expenditure. Prehistoric ancestors of humans experienced long periods of food scarcity, so energy conservation and storage during times of food availability had a survival advantage.

Diagnositic Criteria for Overweight:
The diagnosis of obesity in adults is based on calculation of the BMI by dividing the weight in kilograms by the height in meters squared (kg/m2). The calculated BMI can overestimate adiposity in trained athletes or muscular children, but it is generally recognized as the most reliable method to determine healthy and unhealthy adiposity. Other methods of determining adiposity are useful, but are either too expensive to be of practical use in a clinical setting (ultrasound, CT, MRI, DEXA, total body conductivity, air displacement plethysmography), require specialized training (skinfold thickness), have poor reproducibility (waist-hip ratios), or lack extensive normative data in children (bioelectric impedance analysis). Therefore, BMI in combination with clinical assessment is sufficient to make the diagnosis.

Hypokalemia in Children

Definition and Etiology
Hypokalemia is defined as a serum potassium <3.5 mEq/L.

It is a result of potassium losses in excess of replacement. Potassium can be lost through the GI tract as well as the kidneys.

Clinical Presentation and Physical Examination
Symptoms: constipation, fatigue, muscle weakness, and paralysis

Physical examination

• Check for possible irregular heartbeat.
• Evaluate for signs of muscle weakness/paralysis.

Differential Diagnosis

• Decreased intake as a result of low dietary intake or IV fluids without potassium
• Increased GI losses from vomiting, nasogastric suction, or diarrhea
• Increased urinary losses because of loop and thiazide diuretics
• Mineralocorticoid excess
• Liddle syndrome (autosomal dominant with increased sodium resorption)
• Bartter or Gitelman syndromes

Reye’s Syndrome

An acute childhood illness, Reye’s syndrome causes fatty infiltration of the liver with concurrent hyperammonemia, encephalopathy, and increased intracranial pressure (ICP). In addition, fatty infiltration of the kidneys, brain, and myocardium may occur.
Reye’s syndrome affects children. It’s most common in patients ages 4 to 12, with a peak incidence at age 6.
The prognosis depends on the severity of central nervous system depression. Previously, mortality was as high as 90%. Today, ICP monitoring and, consequently, early treatment of increased ICP, along with other treatment measures, have cut mortality to about 20%. Death is usually a result of cerebral edema or respiratory arrest. Comatose patients who survive may have residual brain damage.

Causes
Incidence of Reye’s syndrome usually rises during influenza outbreaks and is linked to aspirin use. It almost always follows within 1 to 3 days of an acute viral infection, such as an upper respiratory tract infection, type B influenza, or varicella (chickenpox).
With Reye’s syndrome, damaged hepatic mitochondria disrupt the urea cycle, which normally changes ammonia to urea for its excretion from the body. This results in hyperammonemia, hypoglycemia, and an increase in serum short-chain fatty acids, leading to encephalopathy. Simultaneously, fatty infiltration is found in renal tubular cells, neuronal tissue, and muscle tissue, including the heart.

Signs and symptoms
Reye’s syndrome develops in five stages, but the severity of the child’s signs and symptoms varies with the degree of encephalopathy and cerebral edema. Infants may have atypical presentation.
After the initial viral infection, a brief recovery period follows when the child doesn’t seem seriously ill. A few days later, he develops intractable vomiting, lethargy, rapidly changing mental status (mild to severe agitation, confusion, irritability, delirium), hyperactive reflexes, and rising blood pressure, respiratory rate, and pulse rate.
Reye’s syndrome may progress to coma. As the coma deepens, seizures develop, followed by decreased tendon reflexes and, commonly, respiratory failure.
Increased ICP, a serious complication, results from cerebral edema. Such edema may develop as a result of acidosis, increased cerebral metabolic rate, or an impaired autoregulatory mechanism.

Tay-Sachs Disease

The most common of the lipid storage diseases, Tay-Sachs disease results from a congenital deficiency of the enzyme hexosaminidase A. It’s characterized by progressive mental and motor deterioration and is usually fatal before age 5, although some adolescents and adults with variations of hexosaminidase A deficiency have been noted.

Causes
Tay-Sachs disease (also known as GM2 gangliosidosis) is an autosomal recessive disorder in which the enzyme hexosaminidase A is virtually absent or deficient. This enzyme is necessary for metabolism of gangliosides, water-soluble glycolipids found primarily in central nervous system (CNS) tissues. Without hexosaminidase A, accumulating lipid pigments distend and progressively destroy and demyelinate CNS cells.
Tay-Sachs disease strikes persons of Eastern European Jewish (Ashkenazi) ancestry more often than the general population, occurring in about 1 in 2,500 live births in this ethnic group. About 1 in 25 Ashkenazi Jews are heterozygous carriers.

Pediatric Beriberi

The cause of beriberi was determined to be deficiency of thiamine (vitamin B1), a water-soluble and heat-labile vitamin required for carbohydrate metabolism. Thiamine is essential for most vertebrates and some microorganisms. Beriberi has 2 main forms in humans, depending on the system of maximum involvement. Wet (edematous) beriberi is a cardiovascular dysfunction that is usually chronic but may have an acute presentation. Dry beriberi is a multifocal peripheral and/or central neurologic dysfunction, which includes Wernicke encephalopathy and Korsakoff syndrome. Often times, patients present with involvement of both systems.

Pathophysiology
Thiamine mainly functions as thiamine pyrophosphate (TPP), which serves as a prosthetic group or cofactor for 3 enzymes essential to carbohydrate metabolism. Pyruvate dehydrogenase is the last step in the catabolism of glucose for energy, glycolysis, and yields acetyl coA, which is required to synthesize acetylcholine, an important neurotransmitter.

Impaired energy production, increased manufacturing of free radicals, decreases in neurotransmitters, and possible N -methyl-D-aspartate (NMDA) receptor–mediated toxicity have been hypothesized to yield the neuronal injury seen in dry beriberi.

Sources of Thiamine
Thiamine is not widely distributed in high concentrations; consequently, many foods are now routinely fortified with it. Rich natural sources include whole grains, lean pork, peas, spinach, and legumes. Very little thiamine is present in fats, oils, and refined sugars. It is destroyed by heat, pasteurization, and ionizing radiation. Freezing does not affect the bioavailability of thiamine; however, it is insoluble in alcohol. The risk of beriberi increases in individuals who consume a diet high in thiaminase rich foods (eg, raw freshwater fish or shellfish, ferns), a diet high in antithiamine factors (eg, tea, coffee, betel nuts), or both.

Introduction to Hypocalcemia

Hypocalcemia is a laboratory and clinical abnormality that is observed with relative frequency, especially in neonatal pediatric patients.

Definition
Hypocalcemia is defined as a total serum calcium concentration of less than 2.1 mmol/L (8.5 mg/dL) in children, less than 2 mmol/L (8 mg/dL) in term neonates, and less than 1.75 mmol/L (7 mg/dL) in preterm neonates.

Hypocalcaemia is one of the commonest disorders of mineral metabolism seen in children and can be a consequence of several different aetiologies. These include a failure of secretion or action of parathyroid hormone, disorders of vitamin D metabolism and abnormal function of the calcium sensing receptor.

Normal Calcium Metabolism
Calcium is the most abundant mineral in the body. Of the body’s total calcium, 99% is in bone, and serum levels constitute less than 1%.Various factors regulate the homeostasis of calcium and maintain serum calcium within a narrow range. These include parathormone (PTH), vitamin D, hepatic and renal function (for conversion of vitamin D to active metabolites), and serum phosphate and magnesium levels.

Although total serum calcium levels are often measured and reported, ionized calcium is the active and physiologically important component.

The concentration of calcium in the serum is critical to many important biologic functions, including the following:

• Calcium messenger system by which extracellular messengers regulate cell function
• Activation of several cellular enzyme cascades
• Smooth muscle and myocardial contraction
• Nerve impulse conduction
• Secretory activity of exocrine glands.

Effects of Hypocalcemia on the Bodily Functions
Hypocalcemia manifests as central nervous system (CNS) irritability and poor muscular contractility. Low calcium levels decrease the threshold of excitation of neurons, causing them to have repetitive responses to a single stimulus. Because neuronal excitability occurs in sensory and motor nerves, hypocalcemia produces a wide range of peripheral and CNS effects, including paresthesias, tetany (ie, contraction of hands, arms, feet, larynx, bronchioles), seizures, and even psychiatric changes in children.

Introduction to Rickets

Introduction

Rickets is a disease of growing bone that is unique to children and adolescents. It is caused by a deficiency or impaired metabolism of vitamin D, magnesium, phosphorus or calcium. It leads to softening and weakening of the bones.

Rickets is among the most frequent childhood diseases in many developing countries. The predominant cause is a vitamin D deficiency, but lack of adequate calcium in the diet may also lead to rickets .

Types of Rickets
Different types have been described and may include:

• Nutritional Rickets
• Vitamin D Resistant Rickets
• Vitamin D Dependent Rickets
•  - Type I
•  - Type II
• Congenital Rickets

Pathophysiology
Vitamin D deficiency rickets occurs when the metabolites of vitamin D are deficient. Less commonly, a dietary deficiency of calcium or phosphorus may also produce rickets. Vitamin D-3 (cholecalciferol) is formed in the skin from a derivative of cholesterol under the stimulus of ultraviolet-B light. It is converted into the active metabolite calcitriol after final hydroxylation in the kidney. Calcitriol acts to regulate the body’s calcium metabolism by the following mechanisms:

(1) it promotes absorption of calcium and phosphorus from the intestine; 

(2) it increases reabsorption of phosphate in the kidney; and, 

(3) it acts on bone to release calcium and phosphate. Calcitriol may also directly facilitate calcification. These actions result in an increase in the concentrations of calcium and phosphorus in extracellular fluid.

Diagnostic Workup For A Child Presenting With Lethargy

A child may present with lethargy, altered mental status or drowsiness. Lethargy can be a manifestation of a number of clinical conditions , ranging from toxic and metabolic conditions to seizures. The differential diagnosis is broad and a proper workup is needed apart from a detailed history and physical examination.

Laboratory Data

Basic Metabolic Panel
Electrolyte abnormalities ( hypo/hypernatremia, hypo/hyperkalemia, hypo/hypercalcemia ) and hypo/hyperglycemia can present with alteration of mental status. Matabolic acidosis may point to an underlying metabolic disorder or intoxication. Respiratory acidosis can be seen in intoxications with alcohol, benzodiazepines and barbiturates.

Renal and Hepatic Profile
Can indicate acute or chronic end organ dysfunction.

CBC with differentials
Elevated WBC count may indicate acute infection.

Toxicology Screening and Drug levels
Based on patient’s history, order blood levels of prescription medications, ingested medications or substances of abuse.

ABGs
Obtain if hypoxia or acid base problems are suggested by history or physical examination.

Hunter Syndrome - A Rare Genetic Disorder

Introduction:
Hunter syndrome is a rare genetic disorder that occurs due to a deficiency of an enzyme. It is a Lysosomal storage disease and the deficient enzyme is iduronate-2-sulfatase. As a result the long chain of sugar molecules ( mucopolysaccarides) are not broken down by the body and start to accumulate. The accumulated substrates are heparan sulphate and dermatan sulphate. This syndrome has X linked inheritance and so the boys are mostly affected. It is also known as Mucopolysaccharidosis II.

Clinical Features:
The symptoms of Hunter syndrome are usually not apparent at birth. The signs and symptoms usually start to appear around the age of 18 months. The condition varies from patient to patient with some having only minor problems while others showing very sever problems. The signs and symptoms include:

• Growth delay resulting in a short stature
• Delayed development with late walking.
• Change in facial features like thickening of the lips, tongue and nostrils.
• Aggressive behavior.
• Mental function getting worse over time with intellectual disability.
• Claw like hands
• Abnormal bone size and skeletal irregularities.
• Enlarged internal organs like liver and spleen leading to a distended abdomen
• Abdominal hernias.
• Recurrent ear infections, runny nose and cold.
• Deafness getting worse over time.
• Joint stiffness.
• Cardiovascular disorders like progressive thickening of heart valves leading to impaired heart function, high blood pressure and obstruction of blood vessels.
• Respiratory difficulties.
• Carpal tunnel syndrome.