Question

Patient Information: First Name: Jeremiah Last name: Lambert Date of Birth: 11/02/2013 Gender: Male Ethnicity: Swiss German (Wenger Mennonite) Patient History: Weak sucking ability at birth o Mother advised to use a bottle Overall height of patient below average Unexplained episodes of muscle rigidity (hypertonia) Unexplained episodes of muscle limpness (hypotonia) Family History: . Mother delivered prematurely Both siblings (brother and sister) present with same symptoms o Brother: 5 years old o Sister: 4 months old Symptoms Today: Poor Appetite o Resulting in extensive weight loss » Seizure Lethargy paired with an irregular sleep pattern Urine sample smells sweet

Answer 1

1) The symptoms of both patients indicate Maple syrup urine disease (MSUD). It is also called as branched chain ketoaciduria and it is an autosomal recessive disease. The disease is caused by mutations in BCKDHA, BCKDHB, DBT, DLD genes. These four genes codes for the ezymes that work together as the branched-chain alpha-keto acid dehydrogenase complex. This enzyme complex is essential for breaking down the amino acids leucine, isoleucine, and valine. Deficiency of this enzyme complex due to mutation of any one of the gene prevents the breakdown of isoleucine, leucine, and valine. So, when the patient eats protein rich food or food with any of the amino acid present it it, they will not be broken down. As a result, these amino acids and their by-products build up in the body and are released via urine.

2) The symptoms such as sweet smell of urine, anorexia, weight loss, lethargy, hypertonia, hypotonia and seizures are the key information from the file that can be used for diagnosis of this disease.