Dr Ira Shah
M.D, DNB, DCH(Gold Medalist), FCPS

A 3 days old male child born of third degree consanguineous marriage presented with anuria since 24 hours and lethargy since 6 hours. He was a full term emergency LSCS delivery in view of pregnancy induced hypertension in mother. There was no history of maternal drug ingestion or maternal fever antenatally. His birth weight was 3.3 kg and he had a weak cry at birth. He received 2 blood transfusions after birth for pallor. On examination, his weight was 3.3 kg with a height of 48 cms and head circumference of 36.5 cms. There were no dysmorphic features and vital parameters were normal. He had no hypertension and systemic examination was normal. He was given a challenge of 20 cc/kg of Ringer lactate followed by 5 mg/kg of Furosemide; however, he passed only 4.5 ml of urine. Thus he was diagnosed as acute renal failure. His S.Creatinine was 6.7 mg/dl; serum potassium was 6.7 meq/dl with blood gases suggestive of pH of 6.78 with bicarbonate of 3 meq/L. His ultrasound of abdomen showed Right kidney of 5.4 x 3 cm and left kidney of 4.6 x 2.7 cm with normal echotexture and no loss of CMD. In view of his ARF, he underwent peritoneal dialysis and S.Creatinine fell to 3.8 mg/dl with serum potassium of 4.6 meq/L and pH of 7.3 with bicarbonate of 20 meq/L and he started passing urine spontaneously after 36 hours of peritoneal dialysis. In view of high WBC count of 27, 700 cells/cumm (70% polymorphs, 30% lymphocytes) and positive CRP, he was treated with IV cefoperazone and IV Imipenam for 14 days and discharged on oral bicarbonate supplement, calcium and iron supplement.

On Day 21 of life, he was readmitted with cellulitis of right forearm for which he was treated with IV Piperacillin and Ceftizoxime and required a fasciotomy. He was investigated for immunodeficiency and his S.immunoglobulins were suggestive of Hyper IgM syndrome. [Serum IgG <260 mg/dl, serum IgA = 20 mg/dl and serum IgM = 170 mg/dl] in view of low serum IgG & IgA and increased IgM. His CD40 ligand could not be done due to unavailability of the facility. On follow-up his renal parameters are normal and there are no further episodes of infections.

Hyper IgM syndrome is a congenital immunodeficiency that is due to a predominant primary defect of antibody production. Hyper IgM syndrome is genetically heterogeneous. It may be due to 2 genetic mutations on the X chromosome, the CD40 ligand and NEMOgenes or due to 2 genetic mutations on autosomal chromosomes.

X-linked Hyper IgM due to mutation in the CD40 ligand gene is seen in boys and is clinically similar to X-linked agammaglobulinemia. Patients have small tonsils, often no palpable lymphnodes and become symptomatic during the 1st or 2nd year of life with recurrent pyogenic infections. These patients have marked susceptibility to P.carinii pneumonia and are often profoundly neutropenic. There is increased incidence of extensive verruca vulgaris, cryptosporidium enteritis, subsequent liver disease and increased risk of malignancy. Patients have very low serum concentrations of IgG and IgA with normal or elevated concentration of polyclonal IgM. They have normal number of circulating B & T cells. It has a poor prognosis.

X-linked Hyper-IgM due to mutations in NEMOgene is clinically characterized by anhidrotic ectodermal dysplasia. It leads to X-linked dominant incontinentia of pigmenti in females and is lethal in males.

Patients with autosomal Hyper IgM due to ALD mutation present much later in life and do not have susceptibility to P.carinii pneumonia. They have very low concentration of serum IgG, IgA and IgE and markedly elevated IgM. This condition is more benign as compared to boys with CD40 ligand defect.

Patients with autosomal recessive Hyper IgM due to mutations in CD40 are clinically indistinguishable from those with X-linked CD40 ligand defect.

Treatment consists of monthly infusion of IVIg and management of infections with antibiotics. For X-linked CD40 ligand defect early bone marrow transplant is the treatment of choice and prophylaxis for PCP is recommended.