19. One year child is admitted with history of fever and cough had three episodes of bronchiolitis prior now has large foul smelling hat stools which disorder may suspect

A.      Cystic fibrosis

B.      Maple syrup disease

C.       

D.      Bilirubin conjugation defects

Answer is CysticFibrosis

Reference-Biochemical Case Histories [new chapter added in Harper 28^th edition]

A 1-year-old girl, an only child of Caucasian background, was brought to the clinic at the Hospital for Sick Childrenby her mother. She had been feverish for the past 24 h and was coughing frequently. The mother stated that herdaughter had experienced three attacks of "bronchitis" since birth, each of which had been treated with antibioticsby their family physician. The mother had also noted that her daughter had been passing somewhat bulky, foulsmellingstools for the past several months and was not gaining weight as expected. In view of the history ofpulmonary and gastrointestinal problems, the attending physician suspected that the patient might have CF,

although no family history of this condition was elicited.

Laboratory Findings

Chest x-rays showed signs consistent with bronchopneumonia. Culture of sputum revealed predominantlyPseudomonas aeruginosa. Fecal fat was increased. A quantitative pilocarpine iontopheresis sweat test wasperformed, and the sweat Cl– was 70 mmol/L (>60 mmol/L is abnormal); the test was repeated a week later withsimilar results.

Treatment

The child was given an appropriate antibiotic and referred to the cystic fibrosis clinic for further care. Acomprehensive program was instituted to look after all aspects of her health, including psychosocialconsiderations. She was started on a pancreatic enzyme preparation (given with each meal) and placed on ahigh-calorie diet supplemented with multivitamins and vitamin E. Postural drainage was begun for the thickpulmonary secretions. Subsequent infections were treated promptly with appropriate antibiotics and with anaerosolized recombinant preparation of human DNase that digests the DNA of microorganisms present in therespiratory tract. At age 6 years, she had grown normally, had been relatively free of infection for a year, wasattending school and making satisfactory progress. Serious chronic cases of CF in which the lungs are severelycompromised are candidates for lung transplants, although the effiacy of this treatment has been challengedrecently.

Research on gene therapy for CF is under examination (eg, using recombinant viruses encoding the CFTRprotein). Another line of research is investigating whether small molecules can be found for clinical use that helpabnormally folded CFTR molecules re-fold into at least partially active molecules.

Discussion

CF is a prevalent and usually serious genetic disease among whites in North America. It affects approximately1:2500 individuals and is inherited as an autosomal recessive disease; about one person in 25 is a carrier. It is adisease of the exocrine glands, with the respiratory and gastrointestinal tracts being most affected. Adiagnostic hallmark is the presence of high amounts of NaCl in sweat, reflecting an underlying abnormality inexocrine gland function (see below). Pilocarpine iontophoresis has generally been used to allow collection ofsufficient amounts of sweat for analysis. Iontophoresis is a process by which drugs are introduced into the body (inthis case the skin) via use of an electrical current. Its use is diminishing as the availability of specific genetic probes

increases.

The classic presentation of CF is that of a young child with a history of recurrent pulmonary infection and signs ofexocrine insufficiency (eg, fatty, bulky stools due to a lack of pancreatic lipase), as in the present case. However,the disease is clinically heterogeneous, which at least partly reflects heterogeneity at the molecular level Approximately 15% of patients may have sufficient pancreatic function to be classified as "pancreaticsufficient."

For reasons related to abnormalities in Cl– and Na+ transport the pancreatic ducts and the ducts ofcertain other exocrine glands become filled with viscous mucus, which leads to their obstruction. This mucus inalso present in the bronchioles, leading to their obstruction; this favors the growth of certain bacteria (eg,Staphylocococu aureus and P aeruginosa ) that cause recurrent bronchopulmonary infections, eventuallyseriously compromising lung function. In turn, the pulmonary disease can lead to right ventricular hypertrophy andpossible heart failure. Patients usually die of pulmonary infection or heart failure. In recent years, morepatients have been living into their 30s and later, as the condition is now diagnosed earlier and appropriatecomprehensive therapy started. Sometimes, problems due to lack of pancreatic secretions can be present at birth,

the infants presenting with intestinal obstruction due to very thick meconium (meconium ileus). Other patientsless severely affected, may not be diagnosed until they are in their teens or later. CF also affects the genital tractand most males and many females are infertile