A 25 year old boy presented with repeated generalised tonic clonic fits for 3 days. He was diagnosed with Atrial septal defect at the age of 2. His family was unable to afford surgery. He developed seizure disorder on 2nd March 2011 and was seen by a neurologist. MRI brain revealed demyelinating disorder of brain. He went to an advanced cardiothoracic hospital for ASD surgery and was detected to have advanced renal failure (Cr 18) and dialysis initiated.He had anorexia, nausea and vomiting since Oct 2011, had occasional chest pain. He had no edema, polyuria, hematuria, fever, rash, hearing loss or visual disturbance.
He was born in a non-consanguinous marriage, has two sisters apparently normal, the father has diabetes and cancer of mouth. He birth weight was less than normal and was seen by a pediatrician who told them that he had some congenital anomalies but no records are available. He was on Frusemide, Aldosterone, Phenytoin Pantoprazole, Lobazepam.
Upon examination his BP was 170/80, Pallor+, Systemic examination revealed systolic murmur, bilateral fine crackles in both lungs. He has more than normal arched foot, long fingers, receded hairline but was not a typical case of Marphan syndrome. His foot pulses were normal, no pedal edema, and genital were normal.
Investigation:
Urine- Albumin ++, Ph 5, Sp Gr 1015, WBC/RBC 2-3, 24 hr Urine protein 169mg/day. Blood- Urea 141, Creat 6.2, K 5.2, Sugar 135, Protein 7.9, Alb 2.9, Uric 8.3, Calcium 7.5, Phos 4.4, S Alkaline phos 188 IU, SGOT 18, Bil 0.2, Hb 6, TLC 9300, Poly73%, Lympho 17%,M8%,E2%, Hep B, C, HIV Negative. USG Rt kidney 6.2mm, Lt 6.1mm, increased echo with loss of corticomedullary differentiation, no cysts.
CXR- Mild cardiomegaly Echo- Dilated RA, RV, PA. Large Ostium secondum ASD with left to right flow, no PAH , Normal LV. MRI brain – Demyelinating disease involving pontine white matter, internal capsules and corona radiate.
Provisional diagnosis
Chronic tubulointerstitial disease, CKD, ASD, Demyelinating CNS disease, Anemia
Discussion:
In the absence of hypertension till the last stage, absence of edema, bland urine findings and bilateral contracted kidneys, he has chronic interstitial kidney disease. In view of associated congenital involvement of heart, Marphanoid features and and demyelinating CNS disorder, he has unclassified congenital abnormalities of connective tissues (Collagen disorder) probably an X linked recessive disorder. Chromosomal analysis was normal. Genetic studies could not be done on him for lack of facilities
How do I proceed to identify his defect?