Question

The Case Study

The Article: Three year-old Adam presented with a fever and frequent episodes of coughing. He had a history of recurrent pneumonia and sinus infections since he was six months-old, but appeared to be of normal physical and mental function. Adam’s mother had brought him to the doctor’s offi ce for a fever that had started two days earlier. She had started him with liquid Tylenol and had hoped that his fever would go away, but Adam continued to have fever, poor appetite, and sporadic diarrhea. Adam was up-to-date on all vaccinations. When Adam’s mother was questioned about her family history, she told the doctor that she was 36 years-old, and was healthy, while Adam’s father was 42 years-old and had essential hypertension. Adam’s sister was 10 years-old and in good health. Adam’s maternal uncle had died as a child from an unknown infection. No one in the household smoked or used any nonprescription drugs. Household chemicals including cleaning agents and pesticides were stored in child-safe cabinets. Th ey had no household pets. Adam’s vital signs showed his blood pressure was 110/60 mmHg, his pulse 145 bpm, his respiratory rate 32–36 breaths per minute, his temperature 39 degrees Celsius, and his body mass index 14.0 kg/m2. Th e doctor noticed a fl ushed face with a tinge of cyanosis on his lips. Palpitations, dyspnea, and mild rales and rhonchi were noticed throughout both lung fi elds during his physical examination. Adam was placed on oxygen via nasal cannula at 2 L/ min. After 5 minutes on oxygen, his oxygen saturation was obtained by a pulse oximetry and demonstrated 95% saturation. Suspecting a hereditary immune disease, the doctor sent Adam (on oxygen) and his mother to the hospital lab for blood work. Th e blood was drawn for normal electrolyte, hemoglobin, hematocrit, WBC count and diff erential profi le, antibody levels as well as prothrombin time (PT) and partial prothrombin time (PTT). Adam’s mother was instructed to continue giving Tylenol (160 mg/dose, not to exceed four doses/day) until Adam’s lab results were read. Th e lab results revealed sodium concentrations of 135mEq/L, chloride 99mEq/L, potassium 4mEq/L, bicarbonate 22 mEq/L, blood urea nitrogen 15 mg/dL, creatinine 1.0 mg/dL, and glucose 90 mg/dL. Arterial blood gas values were PaCO2 36 mm Hg, PaO2 95 mm Hg, SaO2 97% and pH 7.44. His WBC counts were 4,500/mm3, platelets 140/ mm3, hematocrit of 34, and hemoglobin 2.0% 12 g/dL. WBC diff erential shows Neutrophils 45%, Lymphocytes 40%, Monocytes 4%, Eosinophils 2.0%, and Basophils 1%. His serum immunoglobulins showed IgM 350 mg/dL, IgG 100 mg/dL, IgA 0, and IgE 0. Adam’s PT was 11 sec and PTT was 62 sec. Th e nurse contacted Adam’s mother to let her know that the doctor had ordered a chest X-ray and bronchoscopy based on the lab results. A pediatric pulmonologist, who happened to be in the hospital, was consulted who performed a bronchoscopy in the ER. Pneumocystis jirovecii was quickly identifi ed. A nasal swab displayed gram positive cocci in chains. Th e lung lavage confi rmed P. jirovecii. Chest X-ray showed diff use pneumonia. Th e doctor diagnosed Adam with hyper-IgM syndrome and admitted Adam for observation. Adam was treated with pentamidine nebulizer (300 mg) per protocol. Bactrim (40 mg/kg sulfamethoxazole and 8 mg/kg trimethoprim for 24 hours, given in two divided doses every 12 hours for 10 days) and immunoglobulin therapy (300 mg/kg of body weight every 3 to 4 weeks) was implemented. Blood work was to be repeated to follow immunoglobulin levels, blood cell counts, hemoglobin and hematocrit.

Questions 1. List the abnormal fi ndings, signs, and symptoms in this patient. Explain the cause(s)/mechanism(s) of each.

2. Explain the pathophysiology of hyper-IgM syndrome.

Answer 1

1)The abnormal findings observed were low BP(110/60 mmHg), high pulse (145bpm). the signs observed are flushed face with a tinge of cyanosis on his lips. Symptoms are Palpitations, dyspnea, and mild rales and rhonchi. Due to the abnormal levels obtained in the blood test Chest X-ray was taken and it showed diffuse pneumonia. He has the hyper-IgM syndrome. doctor thought about a heredity immune disease.

2) Patients with HIGM syndrome is not having the ability to change from the production of antibodies of the IgM type to antibodies of the IgG, IgA or IgE types. The patients with this disease have low- levels of IgG and IgA but have a normal level of IgM in their blood. The most common form of HIGM syndrome results from a deficiency of a protein that is mainly found on the surface of T-lymphocytes. The affected protein is called CD40 ligand and this  CD40 ligand is made by a gene on the X-chromosome.so this disease is inherited as an X-linked recessive trait. Only boys get affected by this disorder.

The Inheritance of Hyper IgM Syndromes is due to the X-linked Hyper IgM and NEMO which have immunodeficiency and is inherited as X-linked recessive disorders. if the parents are related prior to marriage.

if the gene gets affected due to mutation is known from in a given family, it is possible to test family members to see if they are carriers of the mutation so that we can avoid the consequences of serious infections.